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Dana-Farber Research News 10.01.2026

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October 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 September 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.

Annals of Oncology

Is it Time to Reassess Standard Toxicity and Patient Reported Outcomes Methodologies for the Adjuvant Use of Immune Checkpoint Inhibitors (ICIs)?

Lyon J, Regan M, McDermott DF

The publication of the five-year efficacy results from the CheckMate-274 trial (Galsky et al, Ann Oncol 2026) has led to new standard of care treatment in high-risk urothelial carcinoma. These results demonstrate nearly doubled median disease-free survival (DFS) in patients treated with adjuvant nivolumab compared to placebo, with interim overall survival (OS) continuing to trend in favour of the immunotherapy arm. The investigators noted “no new safety signals”; but they did not detail the application of immunosuppression, toxicity duration or resolution. This limited reporting of long-term adverse events is similar to the approach taken in other practice changing trials of adjuvant ICIs (Table 1). While these sustained long-term survival curves represent a major therapeutic breakthrough for patients, given the chronic toxicities associated with ICIs, they also prompt reassessment of standard toxicity and patient-reported outcomes methodologies in trials using ICIs in resectable or localized cancers.

 

Annals of Oncology

Lorlatinib Versus Crizotinib as First-Line Treatment for Advanced ALK-Positive Non-Small-Cell Lung Cancer: 7-Year Update from the Phase III CROWN Study

Shaw AT

BACKGROUND: Due to the unprecedented progression-free survival (PFS) benefit with lorlatinib after 5 years of follow-up in the phase III CROWN study, we aimed to quantify long-term outcomes at 7 years.

PATIENTS AND METHODS: Treatment-naive patients (N = 296) with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) were randomly assigned 1:1 to receive lorlatinib 100 mg once a day (n = 149) or crizotinib 250 mg twice a day (n = 147). This post hoc analysis presents investigator-assessed efficacy outcomes, safety, and biomarker analyses.

RESULTS: With a median follow-up of 83.0 and 77.2 months, median PFS was not reached (NR) with lorlatinib [95% confidence interval (CI), 68.5-NR] and was 9.1 months (95% CI 7.4-10.9) with crizotinib [hazard ratio (HR) 0.19, 95% CI 0.13-0.26]; 7-year PFS was 55% and 3%, respectively. With lorlatinib, patients without a PFS event at the end of 24 months had a 79% probability of survival without progression at year 7. No new intracranial progression events occurred after the first 30 months on lorlatinib. Median time to intracranial progression was NR (95% CI NR-NR) with lorlatinib and 16.4 months (95% CI 12.7-21.9) with crizotinib (HR 0.06, 95% CI 0.03-0.12). Overall survival follow-up is ongoing; the number of events for a protocol-specified analysis has not been met. The safety profile was consistent with the 5-year results. With lorlatinib, treatment-related adverse events did not lead to discontinuations after the first 26 months. More genetic alterations were detected in circulating tumor DNA samples from early progressors than in long-term responders on lorlatinib; new potential resistance mechanisms were identified.

CONCLUSIONS: With median PFS yet to be reached after 7 years of follow-up in CROWN, lorlatinib continues to show unprecedented long-term benefit in patients with advanced ALK-positive NSCLC. Patients without progression within 24 months on lorlatinib have a low risk of progression or death at year 7 and may continue long-term treatment. Findings suggest that sustained long-term disease control with first-line lorlatinib may enable advanced ALK-positive NSCLC to evolve toward a chronic condition.

 

Annals of Oncology

Measurement of Ovarian Reserve to Tailor Systemic Therapy Decisions: Future Potential or Ready for Primetime?

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.

 

Annals of Oncology

Updated Results of the POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer) Trial

Niman SM, Gelber RD, Partridge AH

BACKGROUND: In patients with hormone receptor (HR)-positive early breast cancer (BC), the POSITIVE trial demonstrated that temporary interruption of adjuvant endocrine therapy (ET) for pregnancy is feasible and safe in early follow-up (median 41 months). In this article, we report updated results from a preplanned analysis with 2.5 years of additional follow-up.

PATIENTS AND METHODS: POSITIVE, a single-arm prospective trial evaluating temporary interruption of adjuvant ET (after 18-30 months and for up to 2 years) to attempt pregnancy in young patients with BC, enrolled 518 eligible women (?42 years of age, stage I-III BC, desiring pregnancy) from December 2014 to December 2019. Using the bootstrap-matching method, 5-year breast cancer-free interval (BCFI) and distant recurrence-free interval (DRFI) event rates were compared with those of the SOFT/TEXT trials as external controls.

RESULTS: At a median follow-up of 71 months in the POSITIVE cohort and 80 months in the SOFT/TEXT cohort, the 5-year cumulative incidence of BCFI events was 12.3% in POSITIVE and 13.2% in SOFT/TEXT [-0.9% difference, 95% confidence interval (CI) -4.2% to 2.6%]. The 5-year cumulative incidence of DRFI events was 6.2% and 8.3%, respectively (-2.1% difference, 95% CI -4.5% to 0.4%). Among 497 women followed for nondisease outcomes, 377 (76%) had ?1 documented pregnancy on trial, and 343 of 497 (69%) had ?1 live birth, totaling 440 offspring. In an unadjusted analysis comparing the 180 women (36%) who had pre-enrollment embryo/oocyte cryopreservation with those who did not, the 5-year cumulative incidence of BCFI events was 14.0% (95% CI 9.6% to 20.2%) and 11.5% (95% CI 8.4% to 15.7%), respectively.

CONCLUSION: Longer-term follow-up of the POSITIVE trial demonstrates that temporary interruption of ET for pregnancy, including use of fertility preservation, does not increase the risk of BC events. Continued follow-up is warranted given the known risk of late recurrence in this population.

 

Cancer Discovery

O-mannosylation and Protein Maturation Checkpoints Represent Therapeutic Opportunities in BRAF Fusion Protein Oncogenesis

Borgenvik A, Misek SA, Zhang A, Boisvert M, Cai KY, Kovarzin A, Li H, Zhou KN, Gonzalez EM, Goodale A, Lazo de la Vega L, Ragnoni TJ, Persky NS, Abid T, Miglietta EA, Jones JS, Malinowski S, Elsadek LA, Parikh J, Condurat AL, Fultineer A, Choi SH, Ozdemir M, Eisenbies Z, Lee J, Novikov D, Bahadur S, Apfelbaum AA, Robinson J, Clark LM, Schulman N, Lopez G, Tang K, Maldera A, Kwon JJ, Vallurupalli M, Jeon H, Pal S, Golub TR, Hahn WC, Fischer ES, Carpenter AE, Cimini BA, Ligon KL, Janeway KA, Eck MJ, Parker Kerrigan BC, Root DE, Sharifnia T, Beroukhim R, Bandopadhayay P

Fusions between protein-coding genes are common oncogenic drivers, typically pairing a proto-oncogene with a partner that does not independently drive cancer. In all therapeutically actionable fusions, the proto-oncogene is the drug target, the contributions to oncogenicity of the fusion partner have largely been ignored. We studied the role of BRAF fusion partners and found that they are necessary for transformation. In the setting of KIAA1549::BRAF, the most common fusion protein across brain tumors, we found that KIAA1549 is necessary for oncogenicity of KIAA1549::BRAF and engenders a striking and specific dependency on the protein O-mannosyltransferase complex (POMT1/2). Specifically, we show that genetic silencing or pharmacologic inhibition of POMT1/2 reverses fusion-induced transformation, thereby representing a novel and MAPK-independent therapeutic target. Furthermore, POMT1/2 is required to glycosylate and enable maturation of the K::B fusion protein. These findings represent a proof-of-concept for targeting the partners in oncogenic fusions as a potential cancer therapeutic strategy.

 

Cell Genomics

Defining and Cataloging Variants in Pangenome Graphs

Salehi Nowbandegani P, Zhang S, Hu H, Li H, O'Connor LJ

Structural variation causes some human haplotypes to align poorly with the linear reference genome, and this leads to "reference bias." A pangenome reference graph could ameliorate this bias by relating a sample to multiple reference assemblies. However, this approach requires a new definition of a "genetic variant." We define pangenome variants against a reference tree that includes all nodes (sequences) of the pangenome graph but only a subset of its edges; non-reference edges are variant edges. Analyzing the Minigraph-Cactus draft human pangenome reference graph, we identified 29.6 million genetic variants. 3.5 million variants (11.7%) have a reference allele that is not on GRCh38; these variants are difficult to detect without a pangenome reference and are found within tangled, multiallelic regions. We analyze the HLA-A and RHD gene regions and identify thousands of small variants entangled with several structural variants. We release the open-source pantree and a variant call format (VCF) variant catalog.

 

JAMA

Addition of High-Dose Vitamin D3 to Standard Treatment in Patients with Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703)

Ng K, Jackson NA, Kohn CG, Thalappillil JS, Meyerhardt JA

IMPORTANCE: In a phase 2 randomized clinical trial, high-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared with standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC).

OBJECTIVE: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC.

DESIGN, SETTING, AND PARTICIPANTS: Double-blind phase 3 randomized clinical trial enrolling 455 patients with previously untreated mCRC, conducted in the US through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024).

INTERVENTIONS: mFOLFOX6 (modified FOLFOX6 [5-fluorouracil, leucovorin, oxaliplatin]) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab every 2 weeks with either high-dose vitamin D3 (8000 IU daily?×?14 days as loading dose followed by 4000 IU daily) or standard-dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent.

MAIN OUTCOMES AND MEASURES: The primary end point was PFS assessed by the unstratified log-rank test. Secondary end points included objective response rate, overall survival, and toxicity. Prespecified subgroup analyses of PFS were performed according to known prognostic factors.

RESULTS: Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow-up 20 months, the median PFS for high-dose vitamin D3 (n?=?228) was 11.8 months (95% CI, 10.3-13.3) vs 10.3 months (95% CI, 9.4-12.2) for standard-dose vitamin D3 (n?=?227) (1-sided log-rank P?=?.25). There were no significant differences in objective response rate between high-dose and standard-dose vitamin D3 (51% [95% CI, 44%-58%] vs 44% [95% CI, 37%-50%], respectively; P?=?.12), or in overall survival (median, 25.6 vs 27.0 months; 1-sided log-rank P?=?.66). There were no clinically meaningful differences in the most common grade 3 or greater adverse events between the high- and standard-dose groups, including neutropenia (n?=?67 [32%] vs n?=?62 [30%]) and hypertension (n?=?42 [20%] vs n?=?49 [23%]) or in incidence of vitamin D-associated toxicities.

CONCLUSIONS AND RELEVANCE: Among patients with previously untreated mCRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04094688.

 

JAMA Oncology

Modernizing Surrogate Decision-Making to Reflect the Complexity of Cancer Care

Blackstone EC, Sontag DN, Rangachari D, Abel GA

Patients with cancer are at risk of medical decisional incapacity, which poses significant challenges for goal-concordant care. Incapacity necessitates surrogate decision-making, preferably by someone selected in advance by the patient (typically a family member or close friend). The ethical standard by which surrogate decision-makers are expected to make medical decisions is substituted judgment. Rooted in respect for autonomy, this standard requires a surrogate decision-maker to choose what they believe the patient would choose if capacitated. When a patient’s wishes are unknown, the lower standard is to decide what is in the patient’s best interests following the principles of beneficence and nonmaleficence. Decades of research have shown that, in practice, surrogate decision-making does not follow this hierarchy because surrogate decision-makers do not know patient preferences, interject their own values, or do not view substituted judgment as an ideal standard.1-3 In contemporary cancer care, more nuanced, agile, and process-oriented frameworks to support surrogate decision-makers are an unmet need.

 

Journal of Clinical Oncology

Circulating Tumor DNA Profiling Defines Risk Classification in Patients with Ewing Sarcoma: A Report from the Children's Oncology Group and the LEOPARD Study

Shulman DS, Klega K, Chen N, Gohn E, Sexton S, Clinton C, Tanhaemami M, Cibulskis C, Choy E, London WB, Janeway KA, DuBois SG, Crompton BD

PURPOSE: Identification of discrete risk groups remains a high priority for patients with Ewing sarcoma (EWS). We sought to prospectively validate circulating tumor DNA (ctDNA) as a prognostic factor and develop clinical-molecular risk groups.

METHODS: We conducted a prospective investigator-initiated biology study for patients with localized EWS (LEOPARD) and embedded ctDNA analysis into the North American frontline metastatic study AEWS1221. Eligible patients were younger than 50 years with newly diagnosed EWS. All patients provided a baseline blood sample for analysis, which was subjected to ultralow-pass whole-genome sequencing and hybrid capture panel sequencing for ctDNA quantification, fusion detection, and characterization of STAG2 and TP53 alterations. Serial ctDNA sequencing was conducted on a subset of patients in each study. We tested for associations between ctDNA burden and secondary genomic events, and clinical features and outcomes.

RESULTS: One hundred forty patients with localized disease and 255 with metastatic disease provided evaluable pretreatment samples for ctDNA analysis. Elevated baseline ctDNA was associated with stage, tumor size, primary site, indeterminate pulmonary nodules, and metastatic pattern. Elevated pretreatment ctDNA burden was associated with inferior outcomes in patients with localized (n = 140, hazard ratio [HR] = 2.36, P = .032) and metastatic disease (n = 255, HR = 2.15, P = .001). Patients with metastatic disease and TP53 variants and/or persistent on-therapy ctDNA had dismal outcomes. Patients with localized disease, low ctDNA, small tumors, and favorable genomics had no events and constitute a novel low-risk group. Among patients with metastatic disease, those with lung-only disease, low ctDNA, and favorable genomics represent an intermediate-risk group.

CONCLUSION: This study prospectively validates pretreatment ctDNA burden as prognostic in EWS. Risk groups that integrate ctDNA burden with clinical-molecular features differentiate patients with low-, intermediate-, and high-risk disease.

 

Journal of the National Cancer Institute

Survival and Treatment Among Older Patients with Brain Metastases: A Population-Based Study

Grobman B, Lamba N, Catalano PJ, Tanguturi SK, Rahman R, Haas-Kogan DA, Aizer AA

BACKGROUND: Generalizable, large-scale data describing outcomes and treatment approaches for older adults with brain metastases remain limited. In this investigation, we evaluated prognosis and patterns of care in this population over time, with particular attention to the potential impact of social determinants of health.

METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare database to delineate survival, treatment patterns, and disparities among patients aged 65?years and older with brain metastases diagnosed between 2010 and 2020. Survival was assessed with Kaplan-Meier methods and multivariable Cox regression.

RESULTS: This study included 67?832 patients (51% female). The median survival from diagnosis of brain metastases was 3.42?months, improving modestly from 2.99?months in 2010 to 3.88?months in 2019. Higher zip-code level annual income (hazard ratio [HR] = 0.98 per $10?000 increase, 95% confidence interval [CI] = 0.97 to 0.98; P?<?.001) and higher rates of zip-code level high school graduation (HR = 0.98 per 10% increase, 95% CI = 0.97 to 0.99; P?=?.001) were associated with lower mortality. Among patients managed with brain-directed radiation, 62% and 38% received nonstereotactic (inclusive of whole brain radiation) and stereotactic approaches, respectively. Use of stereotactic radiation increased from 22% in 2010 to 54% in 2019. Compared with White patients, Black patients (HR = 0.79, 95% CI = 0.73 to 0.86; P?<?.001) and Hispanic patients (HR = 0.87, 95% CI = 0.79 to 0.95; P?=?.002) were less likely to receive stereotactic radiation.

CONCLUSIONS: The prognosis among older patients with brain metastases remains poor. Many patients continue to receive nonstereotactic approaches. Further work to improve the prognosis of older patients with brain metastases and optimize patterns of care is needed.

 

Molecular Cell

Cyclin E-CDK2 Regulates Cancer Cell Transcriptional Program and Response to Immunotherapy through BRD4

Chu C, Zheng S, Mitchell N, Li Z, Zhang X, Wu X, Zhang T, Dang F, Michowski W, Kolodziejczyk A, Xu ML, Kotowski KW, Yang Z, Martinez-Alonso D, Paulo J, Sheng J, Kirby JA, Groezinger F, Zhou Y, He M, Ito Y, Gulvady AC, Cole MI, Foidart P, Nishida J, Ning X, Sharma S, Suski JM, Fassl A, Zhou Y, Geng Y, Wei W, Gygi SP, Polyak K, Wucherpfennig KW, Sicinski P

The cyclin E-cyclin-dependent kinase 2 (CDK2) complex is a component of mammalian cell-cycle machinery that drives cell division. Hyperactivation of cyclin E-CDK2 is frequent in human cancers. Small-molecule CDK2 inhibitors are tested in clinical trials for cancer patients. Here, we report that cyclin E-CDK2 has a cell-cycle-independent function in regulating the global transcriptional program of cancer cells. CDK2 phosphorylates bromodomain-containing protein-4 (BRD4) and regulates its chromatin association. Overexpression of cyclin E and the resulting activation of CDK2 in cancer cells alter the cancer cell transcriptome, repress the expression of interferon-stimulated genes, and confer resistance to immunotherapy. Conversely, CDK2 inhibition has the opposite effect and augments the efficacy of immune checkpoint blockade. CDK2 inhibition also increases tumor infiltration by dendritic cells (DCs) and enhances antigen cross-presentation to CD8 T cells. These studies reveal an additional function of cyclin E-CDK2 in tumorigenesis and identify inhibition of CDK2 with clinically available compounds as a strategy for enhancing immune checkpoint blockade.

 

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.

 

Nature Medicine

Teclistamab Versus Lenalidomide-Dexamethasone in High-Risk Smoldering Multiple Myeloma: A Randomized Phase 2 Trial

Nadeem O, Cordas Dos Santos DM, Magidson S, O'Donnell E, Redd RA, Liu Y, Midha S, Arters F, Davie C, Ricciardi C, Toenges R, Bidikian N, Hussein S, Alberge JB, Kim S, Pantano-Rubino L, Corrado F, Ashton H, Addonizio D, Mohamed S, Sturtevant A, Marto M, Bergeron A, Malfona F, Panaro K, Richardson PG, Ritz J, Trippa L, Ghobrial IM

Teclistamab, a B cell maturation antigen-targeting bispecific antibody, has demonstrated substantial activity in relapsed multiple myeloma (MM), particularly in earlier lines of therapy, and may have higher efficacy in high-risk smoldering MM (HR-SMM) with a more functional immune system. In the randomized phase 2 ImmunoPRISM trial, we compared fixed-duration teclistamab with lenalidomide-dexamethasone (Rd) in HR-SMM. After a six-patient safety run-in, patients were randomized 2:1 to teclistamab or Rd. The primary endpoint was complete response (CR) rate. As of 26 May 2026, 59 patients were treated-45 received teclistamab and 14 received Rd. Teclistamab treatment induced a CR in 77.8% patients versus 0% with Rd, and minimal residual disease negativity at 10-5 in 82.2% patients. At a median follow-up of 24.5 months, 2-year progression-free survival was 92% with teclistamab versus 49% with Rd. Overall, response rates, duration of response and time to progression (TTP) were significantly improved in teclistamab compared to Rd. Toxicities in the teclistamab arm included grades 1-2 cytokine release syndrome, no neurotoxicity and no increase in grade 3 infections compared to Rd (20% versus 21%). No deaths occurred in either arm. Teclistamab represents a highly active immune-interception strategy for HR-SMM. ClinicalTrials.gov registration: NCT05469893.

 

New England Journal of Medicine

Treatment Decisions in Multiple Myeloma

Mouhieddine TH, Anderson KC

Revolutions in transplantation and targeted and immune therapies have transformed multiple myeloma from a disease with an associated survival of a few years into one for which functional cure is an emerging goal. This abundance of effective therapies has created clinical complexity. Here we provide a practical framework, anchored in trial evidence and informed by emerging biologic discoveries, for the navigation of treatment decisions across the disease spectrum. We outline how cytogenetic and genomic risk stratification, functional fitness, and measurable residual disease status individualize therapy in newly diagnosed disease, in which quadruplet induction therapy is now standard and the role of autologous transplantation is being reevaluated. Regarding relapse, we address the sequencing of B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates, emphasizing T-cell fitness and multiantigen targeting to counter exhaustion and antigen escape. We also consider early interception in high-risk smoldering myeloma. Throughout, we underscore that enrollment of patients in clinical trials should be considered in order to ensure continued progress.

 

Proceedings of the National Academy of Sciences of the U.S.A.

Breast Cancer Prevention by Prophylactic Lalba mRNA-LNP Vaccination

Nishida J, Seehawer M, Rojas Jimenez E, Yan P, Bui TM, Foidart P, Goyette MA, Cai X, Li Z, Polyak K

Tumor-suppressive immunity is more evident in early-stage compared to advanced tumors making it the ideal point for cancer interceptive immunotherapies. We previously described that higher peripheral T cell diversity is associated with more pronounced CD8+ T cell infiltration in ductal carcinoma in situ of the breast, implying a close interaction between peripheral and intratumor immunity. Here, we developed lipid nanoparticle (LNP)-encapsulated messenger ribonucleic acid (mRNA) vaccines expressing the alpha-lactalbumin (LALBA) protein unique to mammary luminal progenitors (LPs) to test whether enhancing immune response by prophylactic vaccination against the putative cell-of-origin of breast cancer suppresses tumorigenesis. Vaccination of outbred Sprague-Dawley rats with N1- methylpseudouridine-modified or unmodified Lalba mRNA-LNP induced different degrees of LALBA-specific and nonspecific immune responses. The vaccination suppressed carcinogen-induced mammary tumorigenesis and improved tumor-free and overall survival without obvious toxicity in the normal mammary glands and other organs. Single-cell transcriptomic analysis revealed that vaccination decreases the frequency of a proliferative LP population in immunoreactive early epithelal hyperplasia. Overall, we provide proof of principle that prophylactic Lalba mRNA-LNP has the potential to suppress the initiation and progression of early breast neoplastic lesions.

 

ACS Medicinal Chemistry Letters

Discovery of JH-XIII-05-01, a First-in-Class Dual IRAK1/IRAK4 Degrader for MYD88 Mutant Lymphomas

Hatcher JM, Liu S, Liu X, Kofides A, Canning AG, Pizzarella D, Tsakmaklis N, Guerrera ML, Patterson CJ, Guijosa A, Gokhale P, Hunter ZR, Sarosiek SR, Castillo JJ, Wang J, Buhrlage SJ, Treon SP

 

American Journal of Hospice and Palliative Care

Large Language Models (LLMs) vs Manual Chart Review for Assessing Goal-Concordant Care: An Exploratory Study

Lindvall C, Liebowitz A, Chang Y, Lakin JR, Tulsky JA, Volandes AE

 

Annals of Internal Medicine

Bereaved Caregivers: Who Is Caring for Them?

Khanna GJ, Morris SE, Leiter RE, Yusufov M

 

Annals of Internal Medicine

The Cardinal in the Bamboo

Drutchas A

 

Annals of Surgical Oncology

ASO Visual Abstract: From Clinical Trial Awareness to Practice-Factors Associated with Intent to Omit Axillary Surgery Based on the SOUND Clinical Trial

Park KU, Delisle M, Hassett MJ, Minami CA, Punglia RS, Woodbury SR, Brindle M, Mittendorf EA, King TA

 

Annals of Surgical Oncology

From Clinical Trial Awareness to Practice: Factors Associated with Intent to Omit Axillary Surgery Based on the SOUND Clinical Trial

Park KU, Delisle M, Hassett MJ, Minami CA, Punglia RS, Woodbury SR, Brindle M, Mittendorf EA, King TA

 
 

Blood Advances

Safe Accelerated Venetoclax Escalation: A Phase 1b Study of Obinutuzumab Plus Venetoclax with Daily Ramp-Up in CLL

Crombie JL, Ahn IE, Ren Y, Tyekucheva S, Carey C, Kniezewski M, Normilus S, Solomon S, Montegaard J, Kim AI, Merryman RW, Armand P, Fisher DC, Brown JR, Davids MS

 

Blood Cancer Discovery

Therapy-Persistent Leukemia is Selectively Vulnerable to SLC23A1 Restoration via Targeting KHSRP

Luo Q, Whalen KS, Wu X, Fortune AL, Garcia JS, Marinchev K, Raulston EG, Nan Y, Booth CAG, Yan K, Root DE, Doench JG, Lane AA

 

BMJ Open

Sexual Health and REhabilitation Online (SHAREonline): Study Protocol of an Optimisation Trial

Miklos EM, Recklitis CJ, Medeiros-Nancarrow C, Bober SL

 
 

Briefings in Bioinformatics

Somatic Likelihood Tiering: An Interpretable Post-Calling Triage Protocol for Tumor-Only Whole-Exome Variant Review

Stawiski K, Kamran SC, Lee J, Bellmunt J, Mouw KW, De Carvalho FLF

 

Cancer

T-Cell Engagers in Small Cell Lung Cancer

Cooper AJ, Sands J

 
 

Cancer Research Communications

The Role of Germline Transposable Element Insertions in Pediatric Cancer Predisposition

Sexton CE, Hamilton KV, Ting DT, Garber JE, Park PJ, Kamihara J

 
 

Cell Reports

Atomistic TCR-pMHC Interactions Bias CD8 Memory Fate within a Single Antigen-Specific Repertoire

Akitsu A, Mallis RJ, Booker MA, Duke-Cohan JS, Brazin KN, Parkins AN, Aryal S, Cinella V, Lee JJ, Uberoy KI, Koenig JK, Biddle M, Messier CM, Lizotte PH, Tolstorukov MY, Reinherz EL

 

Cell Reports Medicine

PARP Inhibition Enhances the Antitumor Activity of HER3-DXd in Non-Small Cell Lung Cancer

Lopez T, Knott A, Soroko KM, Gokhale PC, Jänne PA, Haikala HM

 
 

ESMO Open

Tumor Genomic Landscape of Older Patients with Metastatic Breast Cancer

Gupta H, Brantley KD, Freedman RA, Kodali A, Kirkner GJ, Hughes ME, Higgins A, Newman AB, Avdulla S, Files J, Suggs G, Tolaney SM, Dillon D, Sholl L, Garrido-Castro AC, Cherniack AD, Lin NU

 

European Journal of Cancer

Association of Immune and Proliferation Gene Signatures and Stromal Tumor-Infiltrating Lymphocytes with Clinical Outcomes in Patients with Stage I Triple-Negative Breast Cancer

Tarantino P, Li T, Koca B, Guo R, Cunningham O, Hughes ME, Patel A, King TA, Mittendorf EA, Lin NU, Tayob N, Tolaney SM

 

Expert Opinion on Pharmacotherapy

Current and New Approaches to the Treatment Landscape for Adults with Waldenström Macroglobulinemia

Edwards CV, Castillo JJ, Mouhieddine TH, Sarosiek SR

 
 

Genes and Development

A HUWE1 Regulatory Helix Gates ASCL1 Degradation Through its C-Terminal Phospho-Degron in Small Cell Lung Cancer

Masuzawa K, Dong KD, XiaoYang Hu C, Peng T, Myung Y, Singh S, Li X, Wang T, Jin C, Paulo JA, Yang K, Schmid EW, Booker MA, Li Y, Hong D, Lazo S, Tolstorukov MY, Doench JG, Duplaquet L, Donovan KA, Iqbal S, Fischer ES, Liau BB, Gygi SP, Oser MG

 

Gynecologic Oncology

Molecular Characterization of NSMP Endometrial Cancer and its Relevance for Treatment

Silk T, Matulonis UA, Konstantinopoulos PA

 
 
 

JAMA Dermatology

Comparison of Pleomorphic Dermal Sarcoma to Advanced Cutaneous Squamous Cell Carcinoma and Soft-Tissue Sarcoma

Neff H, Mortelliti C, Kassamali B, Lotter W, Hanrahan G, Solomon B, Karn E, LeBoeuf NR, Gusev A, Ready JE, Nambudiri VE, Ran NA, Silk AW, Ruiz ES

 

JCO Oncology Practice

Biomarker Testing for Non-Small Cell Lung Cancer in Community Practices Operated by an Academic Cancer Center

Farhat K, Paul MA, Roby L, Roberts T, Landry L, Hossaini C, Sulieman R, Lathan C, Johnson BE, Kehl KL

 

Journal of Clinical Investigation

Conserved Neuronal-Like and Secretory Programs Define the Spatial Architecture of Gastroenteropancreatic Neuroendocrine Tumors

Karam J, Hoffman SE, Garza A, Gui D, Hoffman HI, Titchen BM, Tanaka Y, Pimenta E, Pappa T, Valderrabano L, Bi K, Gillani R, Brais L, Shannon E, Hornick JL, Park J, Chan J, Van Allen EM

 
 

Journal of Geriatric Oncology

Hearing Loss: An Unmet Need in Oncology Care

Zhu L, Zhang T, Lam AC, Phelan J, Orav EJ, Lam MB

 

Journal of Nursing Care Quality

Reducing Nighttime Noise with Targeted Room Modifications in a Pediatric Stem Cell Transplant Unit

Waitt JA, Tarquini S, Lehmann LE, Zhou ES

 

Journal of Pain and Symptom Management

End-of-Life Care Patterns by Transplant Eligibility Among Patients with End Stage Kidney Disease

Liu A, Kizza-Brown JFN, Jurdi AA, Malik AM, Sandhu S, Nurhussien L, Horick NK, Obiejesie OE, Bizup G, Safa K, Kalim S, Gelfand S, Lakin J, Tulsky JA, El-Jawahri A, Ufere NN

 

Journal of Palliative Medicine

Evaluating the Performance of Large Language Models on Palliative Care Test Questions: A Mixed Methods Study

Chua IS, Lo YT, Succi MD, Zhang M, Yeh J, Skarf LM, Doyle K, Mazzola E, Bates DW

 

Journal of Palliative Medicine

Racially and Ethnically Marginalized Patients' Perspectives on Nurse-Led Serious Illness Conversations

Tabata-Kelly M, Sheu C, Bulger AL, Ruan M, Gray TF, Healy BJ, Wichmann L, Bernacki RE

 
 

Journal of Surgical Oncology

New Paradigms of Cancer Require New Language: A Qualitative Study Exploring Language for Non-Curative Non-Palliative Cancer Surgery

Wong BO, Farber ON, Reich AJ, Cooper ZR, Mack JW, Clancy TE, Raut CP, Lilley EJ

 

Journal of the European Academy of Dermatology and Venereology

The Patient Behind the Tumour: Host-Related Factors as Determinants of Immunotherapy Efficacy in Advanced cSCC

Ruiz ES, Silk AW

 

Journal of the European Academy of Dermatology and Venereology

Total Margin Control Surgery Achieves Local Control in Four High-Stage Penile Squamous Cell Carcinoma Cases

O'Connell KA, Murad F, Mossanen M, Clinton TN, Schmults CD

 
 

Laryngoscope

Intraoperative Botulinum Toxin and Sialocele Incidence After Parotidectomy

Kons ZA, Jagarlamudi R, Noyes EA, Marcus KS, Rettig EM, Annino DJ, Goguen LA, Uppaluri R, Sethi RKV

 

Leukemia

Macrophage Reprogramming, not CD8 T Cell Dynamics, Characterizes Durable Disease Control Following PD-1 Blockade in Smoldering Myeloma

Perron N, Foster K, Mouhieddine TH, Redd RA, Magidson S, Perry J, Sturtevant A, Davie C, Ricciardi C, Arters F, Marto M, Goguen A, Liu Y, O'Donnell EK, Sperling AS, Laubach JP, Richardson PG, Getz G, Sklavenitis-Pistofidis R, Trippa L, Konishi Y, Nadeem O, Ghobrial IM

 

Molecular Oncology

Tumor B-Cell Infiltration in Platinum-Treated Advanced Muscle-Invasive Urothelial Carcinoma

Stawiski K, Lee J, Michaud DE, Guerriero JL, Mouw KW, Carvalho FLF, Bellmunt J

 
 

Neuro-Oncology

Association Between Radiographic Response and Subsequent Recurrence in Brain Metastases Treated with Radiation: Implications for Response Assessment Criteria

Grobman B, Lamba N, Purohit S, Catalano PJ, Shin KY, Tanguturi SK, Rahman R, Haas-Kogan DA, Aizer AA

 
 

Pediatric Blood and Cancer

ASSIST: Refinement of a Benefits Navigator Intervention Among Low-Income Pediatric Oncology Families

Kellett J, Aziz-Bose R, Kelly CA, Wolfe J, Bona K

 

Pediatric Blood and Cancer

How Clinicians Manage Sleep During Inpatient Hospitalization Following Pediatric Hematopoietic Stem Cell Transplantation

Chevalier L, Robinson E, Weller E, Mintor R, Blacken R, Tarquini S, Warren EAH, Rosenberg AR, Lehmann LE, Zhou ES

 
 
 

Radiotherapy and Oncology

Clinical Outcomes Among Patients Treated with Lu-PSMA-617 and Metastasis-Directed EBRT for Metastatic Prostate Cancer

Adib E, Lee E, Chen YH, Menon K, Killoran JH, Stoltenberg H, Jacene H, Ravi P, Huynh MA

 

Radiotherapy and Oncology

Parametric Delineation of the Clinical Target Volume for Glioma: Model-Based Approach that Tailors to Physician Contouring Practices

Buti G, Ajdari A, Bridge C, Marciscano AE, Sharp GC, Oh K, Shih HA, Bortfeld T

 
 

Translational Oncology

Combined Inhibition of CDK4/6 and PI3K Pathways Exhibit Highly Synergistic Activity and Translational Potential in Ewing Sarcoma

Gloege HF, De Los Santos MAIC, Chakraborty A, Chadha M, Aguilar-Quintero A, Heaslip CO, Finstuen-Magro S, McDannell B, Tanhaemami M, Meyer S, Klega K, Shulman DS, DuBois SG, Blandin AF, Crompton BD