Dana-Farber Research News 08.01.2026
Welcome to Dana-Farber's Research News
August 1, 2026
This twice-monthly newsletter highlights recently published research where Dana-Farber faculty are listed as first or senior authors. The information is pulled from PubMed and this issue notes papers published from July 1 - 15.
If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know by emailing dfciresearchnews@dfci.harvard.edu.
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Annals of Oncology Valenza C, Partridge AH Historically, premenopausal patients with hormone receptor (HR)-positive, early-stage breast cancer (eBC) have derived greater benefit from adjuvant chemotherapy than postmenopausal patients. Even among women with tumors classified by genomic testing as having less aggressive biology, a setting in which the cytotoxic contribution of chemotherapy would be expected to be limited or null as observed in postmenopausal patients, several trials comparing adjuvant chemoendocrine therapy (CET) with endocrine therapy (ET) alone have shown a chemotherapy benefit among premenopausal patients. This additional benefit has been attributed to not only the more aggressive disease that develops in young patients, necessitating the direct tumor-cytotoxic effects of chemotherapy, but also to its chemoendocrine effect, mediated by chemotherapy-induced ovarian toxicity and consequent estradiol suppression. Much indirect evidence supports the substantial impact of the latter mechanism, including the consistent demonstration that premenopausal patients who experience permanent chemotherapy-related amenorrhea (CRA) have lower risk of disease recurrence than those with persistent menstrual cycles or menstrual recovery after transient CRA. |
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Annals of Oncology Aldea M, Lenahan SM, Locquet MA, Liao L, Odintsov I, Wang X, Pecci F, Garbo E, Nakazawa S, Kulesza J, Tsai JA, Simon S, Rossato de Almeida G, Huang J, Paoloni F, Gariazzo E, Santo V, Marks JA, LoPiccolo J, Florez N, Ricciuti B, Luo J, Barbie DA, Rotow JK, Feng WW, Sholl L, Shaw AT, Jänne PA BACKGROUND: Homozygous loss of methylthioadenosine phosphorylase (MTAP) occurs in ?15% of cancers and leads to partial PRMT5 inhibition, creating a selective vulnerability to PRMT5 inhibitors. The frequency and therapeutic relevance of MTAP loss in oncogene-driven non-small-cell lung cancers (NSCLCs) remain underexplored. METHODS: MTAP status was assessed by next-generation sequencing (NGS) or immunohistochemistry (IHC) in >13 000 NSCLC samples in four cohorts. Prevalence was assessed across oncogenic drivers and temporal dynamics in pre- and post-treatment biopsies. Clinical outcomes were analyzed in EGFR- and ALK-rearranged NSCLC treated with first-line osimertinib and alectinib, respectively. The methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor BMS-986504 was tested alone and in combination with targeted therapies (TT) in MTAP-deleted models in vitro, ex vivo, and in vivo. RESULTS: MTAP loss was frequent in ALK-rearranged (27% and 33% by NGS; 36% and 45% IHC), RET-rearranged (18.5% and 26% by NGS; 35% by IHC), and EGFR-mutant NSCLC (17% and 24% by NGS; 24% and 29% by IHC), with CDKN2A co-deletion in 98% of cases. MTAP loss was typically present before TT. MTAP loss did not significantly impact response or overall survival with first-line osimertinib or alectinib in EGFR-mutant and ALK-rearranged NSCLC, respectively. In preclinical studies, BMS-986504 showed nanomolar activity in 11/18 MTAP-deleted models, including 5/8 EGFR- and 5/5 ALK-driven models, regardless of TT sensitivity. Synergistic or additive effects with TT were observed in 11/18 models. In ex vivo ALK-rearranged spheroids resistant to crizotinib, the combination of BMS-986504 and alectinib improved antitumor activity over monotherapy. In an osimertinib-resistant, EGFR-mutant patient-derived xenograft model, BMS-986504 with or without osimertinib controlled tumor growth, without weight loss. CONCLUSIONS: MTAP loss is frequent in oncogene-driven NSCLC, particularly in ALK-, RET-, and EGFR-altered subtypes. MTA-cooperative PRMT5 inhibition demonstrates broad activity in MTAP-deleted, oncogene-driven models and, and may enhance targeted therapy efficacy in selected settings. |
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Annals of Oncology Choueiri TK, McDermott DF BACKGROUND: Nivolumab plus ipilimumab (NIVO + IPI) demonstrated significant long-term survival and response benefits in patients with previously untreated advanced renal cell carcinoma (aRCC) in the phase III CheckMate 214 trial (NCT02231749). We report final efficacy and safety results with 9.3 years median follow-up. PATIENTS AND METHODS: Patients (N = 1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks × four doses, followed by NIVO (3 mg/kg or 240 mg every 2 weeks or 480 mg every 4 weeks); or sunitinib (SUN) (50 mg) once daily (4 weeks on, 2 weeks off). ENDPOINTS: overall survival (OS), and independent radiology review committee-assessed progression-free survival and objective response rate in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk (primary), intention-to-treat (secondary), and IMDC favorable-risk (exploratory) patients. RESULTS: With a median (range) follow-up of 9.3 years (8.6-9.9 years), the hazard ratio (95% confidence interval) for OS with NIVO + IPI versus SUN was 0.71 (0.62-0.82) in intention-to-treat patients, 0.69 (0.59-0.81) in intermediate/poor-risk patients, and 0.80 (0.59-1.09) in favorable-risk patients; 108-month OS probabilities were 31.4% versus 19.5%, 30.2% versus 18.7%, and 35.3% versus 21.8%, respectively. Progression-free survival probabilities at 96 months were 22.7% versus 9.0% (intention-to-treat), 25.4% versus 8.5% (intermediate/poor risk), and 12.5% versus 11.3% (favorable risk). Probabilities of remaining in response at 96 months with NIVO + IPI versus SUN were 48.0% versus 19.0% (intention-to-treat), 50.0% versus 23.0% (intermediate/poor risk), and 36.0% versus not estimable (favorable risk). Incidence of any-grade (grade 3-4) treatment-related adverse events (AEs) was 94.1% (48.6%) with NIVO + IPI versus 97.6% (64.1%) with SUN. Exploratory post hoc analyses reported include descriptive analyses of OS by immune-mediated AE discontinuation status. CONCLUSIONS: In the longest phase III follow-up of a first-line checkpoint inhibitor combination in aRCC (>9 years), NIVO + IPI maintained a substantial survival benefit with durable responses versus SUN. Grade 3-4 treatment-related AEs were lower with NIVO + IPI versus SUN at 9 years. NIVO + IPI remains a first-line standard of care in aRCC. |
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Blood Tagraxofusp, Azacitidine, and Venetoclax in Blastic Plasmacytoid Dendritic Cell Neoplasm Lane AA, Luskin MR, Keating JH, Garcia JS, Shimony S, Leonard R, Goodpaster A, Nguyen T, Galinsky I, Eberly Puleo A Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an orphan, aggressive hematologic malignancy characterized by high CD123 expression. Tagraxofusp (TAG), a CD123-directed toxin, is the only approved therapy. Prior studies demonstrated BPDCN dependence on BCL2, sensitivity to venetoclax (VEN), and reversal of TAG resistance with azacitidine (AZA). We conducted a phase 2 study evaluating combination therapy with TAG, AZA, and VEN in patients with BPDCN (NCT03113643). Patients with previously untreated (1L) or relapsed/refractory (R/R) BPDCN received 28-day cycles of AZA (75 mg/m² days 1-7), VEN (400 mg days 1-21), and TAG (12 µg/kg days 4-6). Eligibility followed TAG guidelines to mitigate risk of capillary leak syndrome (CLS). Twenty-seven patients were enrolled (16 1L, 11 R/R), with median age of 70 years (range 21-81). Composite complete remission (CR/CRi/CRc) rates were 88% in 1L and 64% in R/R cohorts. Median duration of response was not reached in 1L and was 7.2 months in R/R patients. CLS occurred in 15% of patients; most were grade 2. In the 1L cohort, median overall and progression-free survival were not reached; the 2-year overall survival was 65% and 2-year progression-free survival was 53%. Median overall survival in R/R patients was 8.4 months. A high proportion of patients proceeded to allogeneic stem cell transplantation in remission (63% 1L, including 10 of 11 patients age 75 or younger; and 55% R/R). TAG-AZA-VEN is highly active in both untreated and relapsed BPDCN with a predictable and manageable safety profile, supporting its use as a new therapeutic option. |
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Blood Wu CJ Remarkable progress in the understanding of disease pathogenesis and treatment across hematologic malignancies has been achieved in the past 2 decades. Nevertheless, the reliable elimination of disease remains elusive for many cancers. Chronic lymphocytic leukemia (CLL) exemplifies the needs that must be addressed to close the gap between discovery science and the remaining clinical challenges. In CLL, targeted therapies have substantially prolonged survival and enabled long-term disease control for many patients. However, curative outcomes remain exceptional, particularly in high-risk groups such as those with TP53 disruption, dual resistance to Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors, or transformation to aggressive lymphoma. Recent insights into the interconnection between cancer and immunity have positioned CLL as a model example of cancer-associated immunodeficiency, a realization brought into sharp focus by the severe acute respiratory syndrome coronavirus 2 pandemic during which patients with CLL were at extremely high-risk for infection and poor outcomes. Therefore, complications related to infections, autoimmunity, and secondary cancers continue to contribute substantially to morbidity and mortality, underscoring the need for research on immune dysfunction in CLL. Furthermore, pronounced heterogeneity in disease progression and therapeutic resistance highlight the need for mechanistic studies to clarify these distinct biological patterns. Advances in these areas not only hold the promise of curative therapy for broader patient subgroups in CLL but will also inform innovation in research on other cancers, particularly in establishing a molecular definition of disease and defining those interactions with the underlying and resultant immune deficiencies. |
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Cancer Cell Dendritic Cell Redundancy Enables Priming of Anti-Tumor CD4(+) T Cells in Pancreatic Cancer Kureshi CTS, Walsh MJ, Kureshi R, Cardot-Ruffino V, Agardy DA, Ali LR, Qiang L, Shen J, Zuo C, Lenehan PJ, Wang SJ, Chang E, Remland J, Brais L, Clancy TE, Cleary JM, Hornick JL, Huffman BM, Mancias JD, Molina G, Fairweather M, Nowak JA, Perez KJ, Rubinson DA, Slater S, van Dams R, Wang J, Wolpin BM, Zhao L, Singh H, Dougan M, Dougan SK Pancreatic ductal adenocarcinoma (PDAC) is resistant to current immunotherapies and lacks effective anti-tumor CD8+ T cells, which is potentially due to insufficient cross-presentation by cDC1s. Here, we combine a STING agonist with anti-CTLA-4 and anti-PD-1 to achieve durable remissions and immunologic memory in multiple mouse models of poorly immunogenic PDAC. We find that tumor control does not depend on CD8+ T cells or tumor cell MHC expression but instead requires IFN?-producing CD4+ T cells (Th1s) that are primed by dendritic cells in lymph nodes. The triple combination immunotherapy induces an accumulation of activated cDC2s carrying tumor antigen into tumor-draining lymph nodes; cDC2s are required for orthotopic tumor clearance. Intratumoral CD4+ T cells and cDC2s remain present in treatment-naive and chemotherapy-exposed human PDAC. In chemotherapy-exposed patients' blood, cDC2s outnumber cDC1s by 10-fold. Therefore, therapeutic targeting of the cDC2-CD4+ T cell-IFN? axis could be efficacious in PDAC. |
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Cancer Cell Whole-Genome Doubling Drives Immune Evasion by Silencing Antigen Presentation Foidart P, Li Z, Cai X, Seehawer M, Tawawalla A, Baldominos P, Parvin S, Nishida J, Rojas-Jimenez E, Bui TM, Diciaccio B, Goyette MA, Scales T, Yan P, Qiu X, Li R, Jiang Y, Xie Y, Huang XY, Stevens LE, Cejas P, Letai AG, Long HW, Agudo J, Polyak K Whole-genome doubling (WGD) is a common yet poorly understood event associated with poor clinical outcomes. Here, we characterize mechanisms by which WGD drives tumor evolution, utilizing mouse mammary tumor models of WGD established through cell fusion. We find that WGD increases transcriptomic and epigenetic heterogeneity and identify the YM155 BIRC5 inhibitor as a compound specifically suppressing WGD+ tumors. WGD triggers immune evasion by escaping CD8+ T cell responses, rendering WGD+ tumors more sensitive to anti-PD-L1. Through single-cell profiling, we discover that WGD+ cancer cells exhibit reduced antigen presentation and response to IFN?, attributed to the epigenetic silencing of MHCI transcriptional regulators via elevated histone H3 lysine 27 trimethylation. Further investigations reveal decreased KDM6 activity and increased succinate levels in WGD+ tumors. PRC2 inhibition preferentially suppresses WGD+ tumor growth, enhances antigen presentation, and CD8+ T cell infiltration. Our results underscore metabolic and epigenetic alterations as critical drivers of WGD-associated immune escape. |
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Cancer Discovery CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-Driven Alveolar Rhabdomyosarcoma Zhang S, Engel KL, Ross KN, Alexe G, DiGiovanni G, Taillon A, Tong V, Basanthakumar A, Rees MG, Roth JA, Stegmaier K Alveolar rhabdomyosarcoma (aRMS) is a fusion-driven pediatric cancer with poor survival and limited therapeutic options. To uncover novel vulnerabilities, we employed complex-based analysis of the DepMap functional genomic data, identifying CDK8 as a dependency in aRMS. Both CDK8 knockout and pharmacologic inhibition impaired tumor cell growth and induced myogenic differentiation in vitro and in vivo. Compared to genetic loss, CDK8 pharmacologic inhibition induced more dynamic transcriptional changes. With a genome-scale CRISPR-Cas9 drug modifier screen, we determined that the maximal anti-tumor activity of the CDK8 inhibitor requires the presence of the Mediator kinase module, including CDK8, and transcriptional cooperation with the SAGA complex. We further identified SIX4 as a key transcription factor mediating CDK8 inhibitor-induced transcriptional activation of myogenic differentiation genes and impaired tumor proliferation. These findings suggest a distinct gain-of-function mechanism of the CDK8 inhibitor and establish a strong rationale for CDK8 inhibition as a differentiation-inducing therapeutic strategy in aRMS. |
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Cancer Discovery Dias Costa A, Kim S, Hong SC, Yuan C, Qi X, Zhang J, Bleday R, Goldberg J, Irani J, Melnitchouk N, Sicinska ET, Lowder KE, Thalappillil JS, Takashima Y, Väyrynen SA, Payne EM, Meyerhardt JA, Yurgelun MB, Abrams TA, Coleman EC, Fitzpatrick B, Ganser C, Brais LK, Shivdasani RA, Wolpin BM, Nowak JA, Ng K Although vitamin D (VitD) exhibits anti-tumor activity in colorectal cancer (CRC) preclinically, its effects in the human tumor microenvironment (TME) remain unclear. We conducted a randomized, placebo-controlled trial of preoperative high-dose VitD supplementation in stage I-III colon cancer patients to assess its impact on the TME. Forty-two patients received either VitD3 (50,000 IU/day for 7 days, then 10,000 IU/day) or placebo before surgery. Spatial immune-profiling and assessment of VitD receptor (VDR) and CYP27B1 expression were performed on paired tumor samples from 24 patients. VitD significantly increased plasma 25-hydroxyvitamin D levels (P<0.001), increased CD3+CD8+ memory T cells (P=0.03), reduced CD3+CD4+FoxP3+ regulatory T cells (P=0.02) and spatially re-organized the TME, leading to greater T cell and tumor cell proximity. Post-treatment VDR expression was heterogeneous and decreased overall (P=0.02). Spatial transcriptomic profiling of post-treatment resections reflected predominantly repressive VDR activity. These findings support an immunomodulatory role for VitD, warranting further mechanistic investigation. |
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Journal of Clinical Oncology Cleary JM PURPOSE: Presently, to our knowledge, there are no approved targeted therapies for neuregulin 1 gene fusion-positive (NRG1+) cholangiocarcinoma. Zenocutuzumab, a HER2 × HER3 bispecific antibody, is approved for previously treated, advanced/metastatic NRG1+ non-small cell lung cancer and pancreatic adenocarcinoma. Here, we report results for 22 patients with NRG1+ cholangiocarcinoma in the eNRGy trial. METHODS: eNRGy is a single-arm, phase II study of zenocutuzumab in advanced NRG1+ solid tumors. Patients were age 18 years and older and previously treated with or unsuitable for standard therapy. Zenocutuzumab 750 mg was administered intravenously once every 2 weeks. The primary end point was investigator-assessed overall response rate (ORR; RECIST v1.1). Secondary end points included duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS), and safety. RESULTS: As of July 31, 2025, 22 patients (median age 57.5 years) with advanced NRG1+ cholangiocarcinoma were enrolled and had received a median of 1.0 (range, 0-6) prior therapies. In the 18 patients with tumor subtype data available, all had intrahepatic cholangiocarcinoma. Three patients did not meet the protocol-defined criteria for inclusion in the efficacy analysis. Seven of 19 patients achieved a response, resulting in an ORR of 36.8% (95% CI, 16.3 to 61.6). The median DOR was 7.4 months and the median time to response was 1.9 months. The CBR was 57.9% (95% CI, 33.5 to 79.7). Median PFS was 9.2 months (95% CI, 3.9 to 11.1). Most treatment-related adverse events (TRAEs) were grade 1 and 2, and the most common were diarrhea (27.3%), fatigue (18.2%), and nausea (13.6%). One patient had a grade 3 TRAE of anemia. No patients discontinued treatment due to an AE. CONCLUSION: Zenocutuzumab demonstrated clinically meaningful and durable antitumor activity with a favorable safety profile in patients with advanced NRG1+ cholangiocarcinoma. |
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Journal of the National Cancer Institute Worsening Frailty and Declining Quality of Life in Older Durvivors of Non-Metastatic Breast Cancer Minami CA, Lorentzen EH, Mittendorf EA Breast cancer treatment can worsen frailty, but the impact of this decline on long-term quality of life (QoL) remains uncertain. We identified women ?65?years old with non-metastatic breast cancer from the Life and Longevity after Cancer survivorship cohort of the Women's Health Initiative. We examined the association between clinically-significant worsening of frailty, measured by a validated claims-based index one year post-diagnosis, and long-term decline in QoL, assessed on a ten-point scale 4 to 6?years post-diagnosis. Among 1,061 eligible patients, 692 (65.2%) were robust (not living with frailty), 343 (32.3%) were living with pre-frailty, and 26 (2.5%) were living with frailty at cancer diagnosis. Clinically-significant worsening of frailty occurred in 19.5% of patients. In fully adjusted models, worsening frailty was significantly associated with long-term QoL declines (Odds Ratio 1.48; 95% Confidence Interval [1.07 to 2.04]). These findings highlight the need for interventions to prevent worsening frailty during breast cancer treatment. |
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Lancet Davids MS BACKGROUND: Venetoclax-rituximab (VR) following covalent Bruton tyrosine kinase (BTK) inhibitor therapy is the fixed-duration standard of care for patients with chronic lymphocytic leukaemia (including small lymphocytic lymphoma). Pirtobrutinib, a non-covalent BTK inhibitor, is approved for use after treatment with a covalent BTK inhibitor as a continuous therapy option. We aimed to evaluate the addition of pirtobrutinib to VR as a fixed-duration regimen in patients with relapsed or refractory chronic lymphocytic leukaemia. METHODS: This open-label, multicentre, randomised, controlled, phase 3 trial was conducted at 152 sites (comprising community hospitals and academic centres) across 22 countries. Eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic lymphocytic leukaemia (including small lymphocytic lymphoma), and had previously been treated with at least one line of therapy that could include a covalent BTK inhibitor. Patients who had previously received a non-covalent BTK inhibitor, venetoclax, or another BCL2 inhibitor were not eligible. Enrolled patients were randomly assigned (1:1) using an interactive web-based randomisation system, stratified by del(17p) status and previous exposure to covalent BTK inhibitors, and assigned to receive either pirtobrutinib plus VR (PVR) or VR. Both groups received oral venetoclax (25 cycles) and intravenous rituximab (six cycles); the PVR group also received oral pirtobrutinib for 28 cycles, with a three-cycle pirtobrutinib-rituximab lead-in before venetoclax initiation. For this prespecified interim analysis, the primary endpoint was progression-free survival in the intention-to-treat population, assessed by a masked independent review committee (IRC) as per 2018 International Workshop on Chronic Lymphocytic Leukemia guidelines. Safety analyses were conducted in the safety population, defined as all randomly assigned patients who took at least one dose of any study treatment. All analyses were based on a data cutoff date of Feb 2, 2026. The trial is registered at ClinicalTrials.gov, NCT04965493, and is ongoing but no longer recruiting. FINDINGS: Between Oct 13, 2021, and Oct 28, 2024, 784 patients were screened, of whom 639 were randomly assigned: 321 to the PVR group and 318 to the VR group. The median age of patients was 68·0 years (IQR 60·0-74·0), of whom 439 (69%) were male and 200 (31%) were female. The median number of previous therapies was 2 (IQR 1-3); 510 (80%) of 639 patients had previous exposure to covalent BTK inhibitors, of whom 362 (71%) discontinued their most recent drug of this class owing to progressive disease. At a median follow-up of 27·3 months (IQR 19·5-38·7), PVR showed a significant improvement in IRC-assessed progression-free survival compared with VR (hazard ratio 0·547 [95% CI 0·400-0·748]; p=0·0001). The median 24-month progression-free survival rate was 87% (95% CI 82·3-90·4) in the PVR group versus 72% (65·7-77·0) in the VR group, and the median progression-free survival was not reached (IQR 31·7-not estimable) in the PVR group versus 39·7 months (21·5-50·0) in the VR group. This benefit was consistent across prespecified subgroups, including patients with previous exposure to covalent BTK inhibitors. The most frequent treatment-emergent adverse event of any grade in both groups was diarrhoea, reported in 106 (34%) of 316 patients in the PVR group and 110 (35%) of 311 patients in the VR group. The frequency of treatment-emergent adverse events of grade 3 or higher was similar in both groups (249 [79%] of 316 patients in the PVR group vs 227 [73%] of 311 patients in the VR group); the rate of tumour lysis syndrome of grade 3 or higher was lower in the PVR group (1%; three of 316) than in the VR group (4%; 12 of 311). Rates of atrial fibrillation or flutter of any grade were low (11 [3%] of 316 patients in the PVR group vs eight [3%] of 311 patients in the VR group). Rates of treatment discontinuation owing to treatment-emergent adverse events deemed as related to any of the study drugs were similar: 5% (17 of 316 patients) in the PVR group versus 5% (16 of 311 patients) in the VR group. There were five treatment-related deaths: one in the PVR group and four in the VR group. INTERPRETATION: In patients with previously treated chronic lymphocytic leukaemia, PVR showed significant improvement in progression-free survival compared with VR, with consistent results in patients who had previously received covalent BTK inhibitors and no new safety signals. To our knowledge, these results represent the first randomised phase 3 evidence comparing a novel fixed-duration regimen to the current standard of VR in relapsed or refractory chronic lymphocytic leukaemia, supporting PVR as a potential new standard of care. FUNDING: Eli Lilly and Company. |
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Lancet Systemic Light Chain and Transthyretin Amyloidosis-Treatment Advancements and Future Directions Bianchi G, Cuddy SAM Once rapidly fatal, neglected, and orphan diseases without approved therapeutic options, systemic amyloidoses are now highly treatable. Basic scientific discoveries regarding the molecular mechanisms of transthyretin misfolding and aggregation have driven the development of drugs for the treatment of transthyretin (ATTR) amyloidosis, with six novel therapies approved since 2018. The combination of daratumumab, cyclophosphamide, bortezomib, and dexamethasone was approved for the treatment of light chain (AL) amyloidosis in 2021. Since then, highly effective immunotherapies, such as bispecific T-cell engagers, have been tested in clinical trials in patients with relapsed AL amyloidosis, with unprecedented efficacy. Thus, suspicion of systemic amyloidosis should be raised early in individuals with a suggestive clinical presentation, followed by rapid tissue diagnosis, with appropriate protein typing and prompt commencement of active therapy. These rapid and exciting therapeutic advancements set the stage for this Review on the epidemiology, pathophysiology, and diagnosis of systemic amyloidosis. Through the lens of the molecular mechanisms underlying amyloidosis pathogenesis, we will focus on approved and investigational therapies. We also discuss future directions and challenges concerning a cure for patients with AL or ATTR amyloidosis. |
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Lancet Oncology Now or Later? Switching Therapies in Metastatic Breast Cancer Valenza C, Regan MM, Burstein HJ In contemporary management of patients with hormone receptor-positive, HER2-negative metastatic breast cancer, it is standard to switch therapies at tumour progression, defined by RECIST criteria in clinical trials, and by other measures (many, ironically, considered non-measurable by RECIST) in clinical practice, including subtler radiological changes, findings on examination, rising tumour markers, or increased symptoms related to cancer. Accordingly, in the clinic, a treatment change can be considered for symptomatic progression despite radiologically stable disease, or the same treatment might be continued beyond asymptomatic oligoprogression. These approaches reflect the core goals of controlling tumour-related symptoms, preserving quality of life, and navigating a chronic disease where patients will pursue multiple therapeutic options. |
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Nature A Bayesian Framework for Longitudinal EHR and Genetic Discovery Urbut SM, Ding Y, Nakao T, Koyama S, Misra A, Jiang X, Gaffney L, Hornsby WE, Smoller JW, Gusev A, Natarajan P, Parmigiani G Electronic health records (EHRs) provide rich longitudinal disease histories, but existing methods for analysing these data typically treat diseases in isolation1 and rarely integrate germline genetics. Here we present ALADYNOULLI, a Bayesian generative framework that jointly models longitudinal EHR diagnoses, age and polygenic risk to recover latent time-varying disease signatures and patient-specific signature loadings; the model is formulated as a mixture of probabilities rather than a probability of a mixture2, correctly accommodating simultaneous and chronic conditions. Applied to three independent biobanks (UK Biobank3, Mass General Brigham4 and All of Us; total n?>?683,000) spanning up to 52 years of follow-up and 348 diseases, the model recovers 21 replicable signatures with high cross-cohort composition preservation (median of 80%) and reveals biological subtypes within diagnostic categories (Cohen's d up to 4.25; P???1?×?10-8 for 95% of comparisons). Signatures are concordant with established disease biology: carriers of familial hypercholesterolaemia5 enrich in the cardiovascular signature; carriers of clonal haematopoiesis of indeterminate potential6 in the inflammation signature; and a rare variant burden in LDLR, TTN and BRCA2 (refs. 7,8) aligns with disease specificities. A signature-based genome-wide association study identifies 151 genome-wide significant loci including cardiovascular associations missed by single-trait analyses. An explicit likelihood enables inverse probability weighting for selection bias9 while preserving biological signal. For disease prediction, ALADYNOULLI outperforms Pooled Cohort Equation (PCE), PREVENT and Gail at 1-year and 10-year horizons; disease-level (PheCode) predictions complement code-level foundation models such as Delphi-2M (ref. 10). |
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Nature Casdatifan Shows Durable Response Linked to HIF-2? Biology in Kidney Cancer Choueiri TK, McGregor BA Clear cell renal cell carcinoma (ccRCC) is largely driven by the transcription factor hypoxia-inducible factor 2? (HIF-2?)1. Here we show that monotherapy with casdatifan-an orally bioavailable, potent and selective HIF-2? inhibitor2-produces meaningful, durable antitumour activity with manageable safety in individuals with refractory metastatic ccRCC. Dose-expansion data from the ARC-20 study ( NCT05536141 ) are presented, including for the 100?mg once daily (QD) cohort (n?=?32) and the total cohort (n?=?127). Treatment discontinuation from casdatifan-related adverse events was infrequent (3%), and class-effect toxicities included anaemia and hypoxia. The confirmed objective response rates (ORRs) were 35% (95% confidence intervals (CI) = 19-55%; 100?mg QD) and 31% (95% CI = 23-40%; total); median progression-free survival (PFS) was not estimable (95% CI = 5.7-not estimable; 100?mg QD) and 12.2?months (9.4-20.6; total). Greater maximal reductions in serum erythropoietin were associated with improved clinical outcomes, including a higher ORR (P?=?0.001), lower rates of progressive disease (P?=?0.003) and longer PFS (P?=?0.006). Erythropoietin expression was restricted to cancer cells and was significantly higher at the mRNA level in patients with clinical benefit. Concordantly, HIF-2? protein expression and HIF-2? expression signature were associated with prolonged PFS. Overall, our findings show that casdatifan achieves meaningful, durable responses with manageable safety. These data establish a link between on-target HIF-2? pathway modulation, tumour biology and clinical efficacy. |
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Nature Efficient Near-Telomere-to-Telomere Assembly of Nanopore Simplex Reads Qu H, Park PJ, Li H Telomere-to-telomere (T2T) assembly is the ultimate goal for de novo genome assembly. Existing algorithms1,2 capable of near-T2T assembly all require Oxford Nanopore Technologies (ONT) ultra-long reads, which are costly and experimentally challenging to obtain and are thus often unavailable for samples without established cell lines3. Here we introduce hifiasm (ONT), an algorithm that can produce near-T2T assemblies from standard ONT simplex reads, eliminating the need for ultra-long sequencing. Compared with existing methods, hifiasm (ONT) reduces computational demands by an order of magnitude and reconstructs more chromosomes from telomere to telomere on the same datasets. This advance substantially broadens the feasibility of T2T assembly for applications previously limited by the high cost and experimental requirement of ultra-long reads. |
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Nature Non-Genotoxic Transplantation and in Vivo Selection Through Epitope Editing Casirati G, Cosentino A, Freschi M, Zeng J, Mucci A, Levesque S, Neri N, Drago E, Carzaniga V, Romano F, Mahmoud MS, Chávez-Navarro M, Brendel C, Manis JP, Pellin D, Bauer D, Genovese P The short-term and long-term effects of genotoxic pre-transplant conditioning remain barriers to the broader application of haematopoietic stem/progenitor cell (HSPC) transplantation and gene therapies1-4. Although monoclonal antibodies targeting KIT have been proposed as alternatives to chemotherapy or radiotherapy5-7, their pharmacokinetics hinder clinical applications owing to the risk of depleting transplanted HSPCs. Here, to address this issue, we identified amino acid changes in the extracellular domain of KIT that disrupt the binding of two therapeutic monoclonal antibodies8,9, which impair stem cell factor (SCF)-mediated signalling without affecting KIT expression or functionality. We exploited adenine base editing10 or prime editing11 to efficiently introduce these mutations in HSPCs and combined them with the disruption of the BCL11A erythroid enhancer to promote expression of fetal haemoglobin (HbF)12,13, a therapeutic approach for several haemoglobinopathies. This strategy enables in vivo co-selection of gene-engineered cells to reach the threshold required to provide therapeutic benefit in patients affected by sickle cell disease and ?-thalassaemia. We show progressive enrichment of KIT plus BCL11A multiplex-edited haematopoiesis under selective pressure with KIT monoclonal antibody, in vitro and in vivo. We report that extended treatment with anti-KIT regimens leads to superior in vivo enrichment while avoiding clonal selection, as assessed by a lentiviral barcoded library. Finally, by overcoming the limitations of monoclonal antibody pharmacokinetics, epitope editing enables novel haematopoietic replacement regimens that are not limited by on-target graft elimination, allowing prolonged immune-based conditioning that maximizes haematopoietic niche clearance without chemo-radiotherapy or monoclonal antibody wash-out. |
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Nature Chemical Biology A Druggable Redox Switch on SHP1 Controls Macrophage Inflammation Ng MY, Burger N, Shin S, Takeda H, Cheah Xin Yan M, Zhang B, Xiao H, Wei SM, Seo HS, Dhe-Paganon S, Mills EL, Che J, Chouchani ET Immunological proteins are major disease targets, yet most remain undrugged. Post-translational redox modification of cysteine residues has emerged as an important mode of immune cell regulation, particularly in macrophage cytokine responses. Here we develop a strategy for systematic discovery and small-molecule functionalization of redox-regulated cysteines on immunological proteins. Using deep redox proteomics, we annotate 788 in vivo redox-regulated cysteines across diverse immune-relevant protein domains. We demonstrate how these sites enable cysteine-directed pharmacology through discovery of a novel cysteine activation site on the immune regulator SHP1. Targeting C102, we develop a highly selective covalent agonist, SCA, which binds the N-SH2 domain to relieve autoinhibition and activate SHP1. In mouse and human macrophages, SCA selectively engages SHP1 C102, antagonizing interleukin-1 receptor-associated kinase signaling and lipopolysaccharide-induced proinflammatory cytokine production. Together, this work identifies a druggable cysteine redox switch controlling macrophage cytokine responses and provides a compendium of redox-regulated sites for therapeutic development. |
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Nature Communications Syed A, Chowdhury D Bifunctional glycosylases, OGG1 for purines and NTH1 for pyrimidines, repair oxidized DNA bases via consecutive glycosylase and AP-lyase reactions, yet their catalytic relationships and lyase activity's biological relevance remain unresolved. Here, we solved crystal structures of archaeal and human Ogg1 and Nth1 captured in key damage-recognition and catalysis-ready states, complemented by ab initio molecular dynamics simulations of their complete reaction trajectories. We thereby define a unified catalytic mechanism for OGG1 and NTH1 conserved over three billion years, distinct from the canonical oxocarbenium-ion mechanism of monofunctional glycosylases. While divergent in their oxidized substrate recognition, their chemistry converged on ribose protonation and ring opening that precede the deglycosylation step. Acid-base catalysis mediated by a conserved aspartate-lysine dyad lowers the C-N bond cleavage barrier, while the excised 8-oxoG base in OGG1 or a conserved aspartate in NTH1 facilitates the AP-lyase reaction. Moreover, structures of human OGG1 bound to product DNA and to product DNA plus a potent small-molecule agonist F51, within the catalytic pocket, reveal that agonists accelerate enzyme turnover by promoting product release. Together, these findings clarify the catalytic logic of bifunctional glycosylases, enabling the development of chemical tools to interrogate lyase activity and therapeutics for oxidative damage in cancer and aging. |
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Nature Genetics U2AF1 Mutations Rescue Deleterious Exon Skipping Induced by KRAS Mutations Walter DM, Cho K, Denney D, Lee IT, Dohlman AB, Heinz JM, Shurberg E, Jiang KX, Gupta AA, Meyerson M The mechanisms by which mutations of splicing factor gene U2AF1 contribute to lung adenocarcinoma pathogenesis are not well understood. Here we used prime editing to modify the endogenous U2AF1 gene in lung adenocarcinoma cells and assessed the impact on alternative splicing. One specific KRAS mutation, G12S, led to skipping of KRAS exon 2 and generation of a nonfunctional KRAS transcript. However, expression of the U2AF1S34F mutant reverted this exon skipping and restored KRAS function, leading to enrichment of U2AF1S34F mutations in KRASG12S-mutant lung adenocarcinomas. Comprehensive analysis of splicing factor-oncogene mutation co-occurrence in cancer genomes also revealed significant coenrichment of KRASQ61R and U2AF1I24T mutations. Experimentally, KRASQ61R mutation led to KRAS exon 3 skipping, which in turn could be rescued by expression of U2AF1I24T. Our findings provide evidence that splicing factor mutations can rescue splicing defects caused by oncogenic mutations in a dynamic process of cascading selection. |
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New England Journal of Medicine Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma Choueiri TK BACKGROUND: Adjuvant pembrolizumab improves disease-free and overall survival among patients with resected clear-cell renal-cell carcinoma. The hypoxia-inducible factor 2? inhibitor belzutifan has activity in advanced disease. Adjuvant pembrolizumab with belzutifan may further improve outcomes in patients with clear-cell renal-cell carcinoma at increased risk for recurrence. METHODS: In this phase 3, double-blind trial, we randomly assigned participants in a 1:1 ratio to receive intravenous pembrolizumab at a dose of 400 mg every 6 weeks (?9 doses) and either daily oral belzutifan at a dose of 120 mg (pembrolizumab-belzutifan) or placebo (pembrolizumab-placebo) for up to 1 year. The primary end point was disease-free survival as assessed by the investigator; secondary end points included overall survival and safety. RESULTS: A total of 921 participants were assigned to receive pembrolizumab-belzutifan and 920 were assigned to receive pembrolizumab-placebo. The median time from randomization to the data-cutoff date (August 23, 2025) was 28.4 months (range, 15.0 to 40.1). Disease-free survival was significantly higher with pembrolizumab-belzutifan than with pembrolizumab-placebo (hazard ratio for disease recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87; two-sided P<0.001); the estimated 24-month disease-free survival was 80.7% and 73.7%, respectively. At this interim analysis with 29% of the final-analysis events observed, overall survival did not differ significantly between the groups (hazard ratio for death, 0.78; 95% CI, 0.51 to 1.19; two-sided P?=?0.24); the estimated 24-month overall survival was 96.2% with pembrolizumab-belzutifan and 95.7% with pembrolizumab-placebo. Adverse events of grade 3 or higher occurred in 52.1% of the participants who received pembrolizumab-belzutifan and in 30.2% of those who received pembrolizumab-placebo. CONCLUSIONS: Treatment with pembrolizumab-belzutifan led to significantly higher disease-free survival, with a greater risk of grade 3 or higher toxic effects, than treatment with pembrolizumab monotherapy after nephrectomy in participants with clear-cell renal-cell carcinoma at increased risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; LITESPARK-022 ClinicalTrials.gov number, NCT05239728.). |
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New England Journal of Medicine Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma Jacobus S, Wei Z, Richardson P Background: Current treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression. The appropriate duration of maintenance therapy with lenalidomide has been unclear. Methods: In this phase 3 trial, we enrolled patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation. After induction treatment with a proteasome inhibitor-lenalidomide combination, patients were randomly assigned to receive indefinite-duration (continuous) lenalidomide or fixed-duration lenalidomide (for 2 years). The primary end point was overall survival; the trial had 80% power to detect a 50% increase in median survival (from 5 years to 7.5 years), with a two-sided alpha level of 5%, 395 patients undergoing randomization, and 204 deaths occurring during 9 years of follow-up. Results: At the end of induction, 516 patients were randomly assigned to the indefinite-duration group (260 patients) or the fixed-duration group (256 patients). At a median follow-up of 86 months, overall survival did not differ significantly between the groups. With 80 deaths in each group, overall survival at 7 years was 68.6% in the indefinite-duration group and 69.0% in the fixed-duration group (difference, -0.4 percentage points; 95 confidence interval [CI], -9.0 to 8.3; P = 0.93). Progression-free survival at 7 years was 36.1% in the indefinite-duration group and 29.7% in the fixed-duration group (difference, 6.4 percentage points; 95% CI, -2.6 to 15.4). The 5-year cumulative incidence of second primary cancers, excluding nonmelanoma skin cancer, was 11.2% with indefinite-duration lenalidomide and 8.3% with fixed-duration lenalidomide. More adverse events occurred with indefinite-duration lenalidomide; the incidence of nonhematologic events of grade 3 or higher was 48.2% with indefinite-duration therapy and 31.5% with fixed-duration therapy. Conclusions: In this phase 3 trial involving patients with standard-risk newly diagnosed multiple myeloma who were not undergoing up-front autologous stem-cell transplantation, indefinite-duration maintenance therapy after induction therapy did not result in significantly longer overall survival than fixed-duration maintenance therapy. (Funded by the National Cancer Institute of the National Institutes of Health and Amgen; ENDURANCE ClinicalTrials.gov number, NCT01863550.). |
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Science A CDK1 Phospho-Switch Reprograms TRAIP to Unload Replisomes in Mitosis Can G, Shyian M, Krishnamoorthy A, Lim Y, Wu A, Zaher MS, Walter JC, Pellman D Cells entering mitosis with incompletely replicated DNA face catastrophic chromosome segregation failure. During interphase, the replisome-associated E3 ubiquitin ligase TRAIP ubiquitylates barriers in front of the fork to allow replisome progression. In mitosis, TRAIP is reprogrammed from a trans-acting to a cis-acting ligase that can ubiquitylate the replisome itself. This enables the processing of unreplicated DNA by promoting replisome disassembly, fork breakage, and joining of the broken chromosome arms. Here, we describe a mechanism for this reprogramming: the ATPase TTF2 is recruited to the replisome, where its noncatalytic N-terminal domain tethers Cyclin B-CDK1-phosphorylated TRAIP to the leading strand DNA polymerase ? in a geometry that allows replisome ubiquitylation. Thus, a phospho-regulated architectural switch alters replisome organization in mitosis to safeguard genome integrity before chromosome segregation. |
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Science Degron-Independent Recruitment of KAT2A Expands the Target Space of CRBN Molecular Glues Ojeda S, Wang M, Baek K, Bourgeois W, Sommerschield A, Yue H, Metivier RJ, Karagiannis P, Levitz TS, Xiong Y, Donovan KA, Armstrong SA, Fischer ES Lysine acetyltransferases (KATs) cooperate with oncogenes such as c-Myc, estrogen receptor, and lysine methyltransferase 2A (KMT2A) fusions to sustain malignant programs. Targeting of KAT proteins has shown clinical efficacy; however, achieving homolog selectivity for most KATs remains a major challenge. By extending cereblon (CRBN)-based molecular glues beyond the canonical degron space, we developed an exquisitely selective degrader of KAT2A. Cryo-electron microscopy revealed that CRBN recruits KAT2A independently of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Selective KAT2A degradation leads to potent ablation of histone H3 lysine 9 acetylation (H3K9Ac), antiproliferative effects in acute myeloid leukemia cell lines, and in vivo efficacy in a patient-derived xenograft model, establishing KAT2A as a targetable vulnerability to treat a wide range of malignancies. More generally, degron-independent recruitment extends the CRBN-targetable proteome. |
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Science Local Signals, Systemic Decline Vander Heiden MG Cachexia — a progressive loss of body mass despite adequate nutrition — is one of the most devastating consequences of cancer. However, its causes are incompletely understood. Increased energy expenditure can contribute to cachexia, but “sickness behaviors,” such as loss of appetite (anorexia), fatigue, reduced activity, and malaise, also often play a part. Several tumor-derived inflammatory molecules act on the brain and peripheral tissues to promote cachexia in some contexts, but targeting these factors has not yet led to effective cachexia treatments. On page 90 of this issue, Cross et al. report that mouse lung tumors bearing mutations in serine/threonine kinase 11 (Stk11, also known as Lkb1) activate vagal sensory neurons through local inflammatory lipid signaling. Notably, a high-fat diet intensifies these sensory nerve signals from the tumor to modulate the brain circuits that control feeding behavior. This mechanism promotes anorexia and cachexia. |
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Science The CARM1 Epigenetic Enzyme Inhibits Cross-Presenting Dendritic Cell Function in Cancer Immunity Zhang X, Xirenayi S, Zhao Y, Han Y, Sobral M, Kang S, Zhang C, Barlow GL, Pyrdol J, Cho JW, Huang K, Ning X, Hemberg M, Van Allen EM, Mooney DJ, Wucherpfennig KW The cancer-immunity cycle requires cross-presenting type I conventional dendritic cells (cDC1s) that induce T cell-mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are currently inadequate. We found the epigenetic enzyme CARM1 (coactivator-associated arginine methyltransferase 1) to be a selective negative regulator of cancer antigen presentation by cDC1s but not cDC2s. Inactivation of the Carm1 gene promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors, and a CARM1 inhibitor enhanced cDC1-mediated priming of T cells by means of a cancer neoantigen vaccine. CARM1 inhibition increased chromatin accessibility at BATF3-Jun and RelA sites that are critical for cDC1 function and activation. Transforming growth factor-? regulated Carm1 expression, which suggests that CARM1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify CARM1 as a potential therapeutic target for enhancing the antitumor function of mouse and human cDC1s. |
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Advances in Radiation Oncology Synergistic Effect of Linebacker-1 with Radiation Therapy in a Mouse Lung Cancer Model Yasmin-Karim S, Richards G, Makrigiorgos GM |
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American Journal of Hematology Davids MS |
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Annals of Surgical Oncology Park KU, Sather BK, Shah A, Minami CA, Butler L, Love JA, McLean K, Dunn A, Mittendorf EA, King TA |
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Annals of Surgical Oncology Shah A, Love JA, Butler M, Butler LN, Mittendorf EA, King TA, Park KU |
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Annals of Surgical Oncology Integrating Generative AI into Nomograms for Breast Cancer Nodal Risk Predictions Shah A, Love JA, Butler M, Butler LN, Mittendorf EA, King TA, Park KU |
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Blood Advances Scheidegger N, Schneider C, Alexe G, Basanthakumar A, Bourgeois WA, Dudkiewicz-Garbicz J, Khalid D, Merickel LA, Perry JA, Salhotra S, Taillon A, Harris MH, Wunderlich M, Armstrong SA, Pollard JA, Pikman Y, Stegmaier K |
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Blood Advances Harris EM, Semedo Tavares EB, Montcrieff C, Chen N, London WB, Grace RF |
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Blood Advances Pizzarella D, Kofides A, Hatcher JM, Liu X, Guijosa A, Tsakmaklis N, Peachey AL, Wang J, Guerrera ML, Patterson CJ, Hunter ZR, Sun H, Sarosiek SR, Castillo JJ, Buhrlage SJ, Dhe-Paganon S, Branagan AR, Treon SP, Liu S |
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Blood Cancer Discovery Laying the Foundation for Clinically Actionable Genomic Subtyping in Diffuse Large B-Cell Lymphoma Shipp MA |
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Blood Cancer Discovery New Insights into the Role of Clonotypic B Cells in Plasma-Cell Neoplasia Kim S, Ghobrial IM |
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Blood Cancer Journal Martindale SP, Azevedo RS, Harrison DA, Tesar B, Stiegler M, Ferre V, Rai V, Ren Y, Zhou Y, Tyekucheva S, Fernandes SM, Machado JH, Kandathilparambil Sasi B, Naeem A, Ott CJ, Brown JR |
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Blood Cancer Journal The Role of RAD23A in DNA Repair and Proteasome-Dependent Protein Degradation in Multiple Myeloma Wan X, Du T, Fang T, Wang M, Ray A, Wen K, Musa MA, Garbicz F, Carrasco RD, Samur AA, Fulciniti M, Talluri S, Song Y, Munshi NC, Anderson KC |
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Blood Cancer Journal Guerrera ML, Liu X, Tsakmaklis N, Peachey AL, Kofides A, Hatcher J, Ramirez Gamero A, Guijosa A, Yang G, Sun H, Liu S, Patterson CJ, Meid K, Flynn C, Carrasco RD, Branagan AR, Sarosiek SR, Castillo JJ, Anderson KC, Munshi N, Treon SP, Hunter ZR |
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Cancer Analysis of a Large Osteosarcoma Sequencing Data Set Elucidates Patterns of Genomic Alterations Bousquet HG, Vega LL, Ceca E, Schiantarelli J, Forrest SJ, Janeway KA |
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Cancer Maintenance Therapy in Gynecologic Malignancies: Current and Future State Widick PC, Wright AA, Liu JF |
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Cancer Shulman DS, Cameron D, Raskin KA, Weil BR, Dubois SG, Weldon CB |
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Cancer Epidemiology, Biomarkers, and Prevention Kauffman TL, O'Donnell EK, Marinac CR, Babic A, Adams K, Beckwith JB, Berman TA, Brantley KD, Chowdhury D, Crompton BD, Diller LR, Elias KM, Feltmate CM, Florez N, Garber JE, Ghobrial I, Hanna GJ, Hormoz S, Kamihara J, LeBoeuf NR, Mittendorf EA, Partridge AH, Rodriguez NJ, Sands J, Thapa B, Weeks LD, Woo SB, Yurgelun MB, Parmigiani G, Rebbeck TR, Syngal S |
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Cancer Nursing Phillips CS, Morris SE, Mazzola E, Xiong N, Hammer M, Ligibel J |
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Cell Death and Differentiation Davern M, Turner CJ, Griffin D, Bencsics L, Chan BC, Kung JY, Olson ML, Walker Williams C, Soni S, Krotee L, Yorsz M, Antonellis G, Lizotte PH, Paweletz CP, Ryan J, Birocchi F, Almazan AJ, Sarosiek KA, Barbie D, Bhola P, Maus MV, Letai A |
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Cell Reports Qian Y, Panaampon J, Chapuy B, Zhang X, Zhao X, Wang Z, Zhang P, Zhang A, Ke Q, Zhong J, Yuan P, Zhang L, Hong M, Choi IK, Guan J, Rodig S, Pozdnyakova O, Wu H, Shipp MA, Dougan SK, Zhang B |
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Clinical Cancer Research Waks AG, Segui E, Li T, Kallfelz E, DiLullo M, Patel A, Rahman T, Junkins K, Rahee H, Frey AM, Kelly E, Stalteri M, Wrabel E, Parsons H, Poorvu PD, Partridge A, Abravanel DL, Poorvu N, LeStage B, Sicinski P, Tolaney SM, Wagle N, Tayob N, Shapiro GI |
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Clinical Cancer Research Huang J, Miller KW, Rotow JK, Mazzola E, Nishino M, Sholl LM, Jänne PA, Barbie DA, Shaw AT, Kehl KL, Luo J |
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Clinical Cancer Research Rotow JK, Ricciuti B, Florez N, Aldea M |
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Communications Biology Cushman CH, Fowler CE, Mazziotta C, Ahmed MM, Bakouny Z, Paulo JA, Rivas HG, DeCaprio JA, Cheng J |
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Environmental Pollution Ugai S, Mizuno H, Matsuda K, Kondo A, Zhong Y, Nakazawa N, Miyahara S, Väyrynen SA, Chan AT, Song M, Giannakis M, Meyerhardt JA, Väyrynen JP, Nowak JA, Ogino S, Ugai T |
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ESMO Open Schlam I, Kim SE, Heiling H, Faggen M, Sinclair N, Sanz-Altamira P, Berwick S, Malcolm A, Varella L, Sammons S, Schumer S, Poorvu PD, Wallace E, Pasternak E, Tayob N, Tolaney SM, Mayer EL |
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Gynecologic Oncology Roller L, Zhou N, Atre I, Xiong N, Li J, Cheng SC, Liu N, Lacad D, Adjei M, Matulonis UA, Konstantinopoulos PA, Liu JF, Tayob N, Stover EH, Shinagare AB |
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Human Vaccines and Immunotherapeutics Elranatamab: A Novel B-Cell Maturation T-Cell Engager Hossain S, Bianchi G |
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Immunotherapy CD137 in Cancer Therapy - Bench to Bedside Rallis KS, Liegel JJ, Pommier A, Ciuculescu MF, Cancelas JA, Avigan DE |
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JAAD Case Reports Kanwar R, Lee MS, Silk AW, LeBoeuf NR, Nambudiri VE |
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JAMA Dermatology Consensus Guidelines for Staging and Surveillance Imaging in Cutaneous Squamous Cell Carcinoma Kassamali B, Schoenfeld JD, Sethi R, Emerick K, Guenette JP, Kelly HR, Lilley EJ, Pashtan I, Silk AW, Ruiz ES |
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JAMA Dermatology ctDNA or Merkel Virus Antibodies for Surveillance of Merkel Cell Carcinoma Recurrence Thakuria M, Silk AW, Khaddour K |
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JAMIA Open Development of a Benchmarking Dataset for Symptom Detection Using Large Language Models Davis J, Durieux BN, Van Dongen C, Sciacca K, Gutierrez JM, Lindvall C |
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JCO Oncology Practice Acupuncture in Cancer Care: Evidence, Safety, and Implementation in Oncology Practice Lu W, Martyniuk I, Bao T |
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JCO Precision Oncology Alcindor T, Papke DJ Jr, Venkataraman V, Wagner MJ, Merriam P, Haddox CL, Wagner AJ, Solimini NL, Jambhekar A, George S |
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JNCI Cancer Spectrum Outcomes and Treatment Patterns in Germline BRCA1/2 Carriers from Two Matched Cohort Studies Morganti S, Kim SE, Jin Q, Cha J, Zeigler JE, Newman AB, Kirkner GJ, Snow C, Zheng Y, Vincuilla J, Parker T, Buehler RM, Bychkovsky BL, Dibble KE, Sella T, Rosenberg SM, Peppercorn J, Guzman-Arocho YD, Come SE, Poorvu PD, Hughes ME, Mittendorf EA, King TA, Lin NU, Garber JE, Tayob N, Tolaney SM, Partridge AH, Lynce F |
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Journal of Clinical Investigation Singh PN, Hadj Bachir E, Cejas P, Madha-Krause S, Epstein CB, Chan JA, Bernstein B, Kulke MH, Shivdasani RA |
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Journal of Clinical Investigation Hao J, Kochupurakkal B, Branigan TB, Somuncu OS, Liu R, Jadhav H, da Costa AAB, Jiao Y, Yu JZ, Martignetti DB, Sadatrezaei G, Mukkavalli S, Gokhale PC, Cheng SC, Skates SJ, Konstantinopoulos PA, Liu JF, Parmar K, D'Andrea AD, Shapiro GI |
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Journal of Clinical Investigation Ananthapadmanabhan V, Bruno S, Vonk L, Cheng YC, Teshager A, Eschle BK, Rodrigues JS, Schnabel J, Kodali A, Gokhale PC, Paulo JA, Li Y, Cherniack AD, Michor F, DeCaprio JA |
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Journal of Geriatric Oncology Hearing Loss: An Unmet Need in Oncology Care Zhu L, Zhang T, Phelan J, Orav EJ, Lam MB |
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Journal of Immunotherapy Cohen JV, Liu M, Rogers G, Manos M, McHugh P, Schwer A, Ott PA, Silk AW, Khaddour K, Buchbinder EI, Gibson WJ, Hodi FS Jr, Tsibris HC |
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Journal for ImmunoTherapy of Cancer Serzan M, Xie W, McGregor BA, Wei X, Mcdermott DF, Choueiri TK |
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Journal of Nuclear Cardiology Immuno-PET in Cardiovascular Disease: Advances, Challenges, and Opportunities Lie W, Djafari Rouhani S, Clark L, Divakaran S, Rashidian M |
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Journal of Pain and Symptom Management Palliative Care in Children with Severe Neurological Impairment: The PediQUEST Refine Case Series Snaman JM, Requena ML, Avery ME, Herold BT, Balossi M, DeCourcey DD, Hauer J, Dussel V, Wolfe J |
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Journal of Palliative Medicine Agaronnik ND, Davis J, Sounack T, Manz CR, Lindvall C |
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Journal of the National Comprehensive Cancer Network Neighborhood Poverty and End-of-Life Care Among Adolescents and Young Adults with Cancer Stal J, Cronin AM, Cernik C, Uno H, Fisher L, Lakin JR, Mack JW |
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Journal of Thoracic Oncology Di Federico A, Cooper AJ, Ricciuti B, Digumarthy S, Alessi JV, Hambelton GM, Pecci F, Makarem M, Gandhi MM, Garbo E, Lamberti G, Haradon J, Nguyen T, Voligny E, Nishino M, Rodig SJ, Pfaff K, Wang X, Sholl LM, Luo J, Johnson BE, Janne PA, Arvind R, Gainor JF, Heist RS, Awad MM |
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Nature Reviews Cancer Context-Dependent Synthetic Lethality - An Emerging Precision Therapeutic Approach Chang L, Shaw K, Vazquez F, Sellers WR |
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Nature Reviews Clinical Oncology The Clinical Landscape of HIF2? Inhibitors in Oncology Saad E, Machaalani M, McDermott DF, Choueiri TK |
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Neurology Characteristics, Diagnosis, and Treatment of Aphasia in Patients with Brain Tumors: A Scoping Review Finnemore A, Miller PJ, Maguire AJ, Vinh J, Caplan D, Wade CG, Tulsky JA, Wright AA, Lindvall C, Rhee JY |
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Oncologist Murchison K, Khaddour K, Camargo A, Ruiz E, Sethi R, Rettig E, Yoon C, Kim EY, DeSimone M, Cohen J, LeBoeuf NR, Ran N, Thakuria M, Silk AW |
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Oral Oncology Bakhtiar M, Al-Inaya Y, Das D, Margalit DN, Tishler RB, Haddad RI, Hanna GJ, Rettig EM, Faden DL, Schoenfeld JD |
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Pediatric Blood and Cancer Bansal S, Snaman JM |
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Pediatric Blood and Cancer Lung Adenocarcinoma and Genetic Cancer Predisposition in an Adolescent Neel DS, Chu D, Jimenez-Kurlander L, Vargas SO, Perkins R, Collins NB |
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Practical Radiation Oncology Pettas E, Woo SB, Margalit DN, Tishler RB, Haddad RI, Hanna GJ, Treister NS |
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Practical Radiation Oncology MRI-Only Simulation for Prostate MRI-Guided SBRT Kinz M, Campbell J, Bullens CL, Kaza E, Hu YH, Ferguson D, Hsu SH, Han Z, Bredfeldt JS, Leeman JE, Sudhyadhom A, Singhrao K |
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Therapeutic Advances in Medical Oncology OX40 Transcriptomic Expression and its Association with Immune Checkpoints and Clinical Outcomes Thapa B |
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Transfusion Close S, Liu J, Abousamra L, Konshina E, Shao C, Green E, Sarhan S, Geary K, Shah S, Manis J, Bae YJ, Maurer R, Cutler C, Mo C, Nikiforow S |