Welcome to Dana-Farber's Research News
February 15, 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 January 16 - 31.
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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Blood How I Approach Clinical Ethics Consultation in Hematology Marron JM, Semler LR, Abel GA Caring for individuals with hematological disorders is increasingly complex, and with medical complexity often comes ethical complexity. Prognostic uncertainty, stakeholder conflicts, and myriad other ethical challenges often contribute to situations that can benefit from ethics support. Through the presentation of three vignettes focusing on ethical dilemmas arising from hematology cases, we review the four phases of clinical ethics consultation: consult triage; ethics consult intake; stakeholder meeting(s) and additional data collection; and ethics analysis and recommendations. In tandem, we review some of the most common ethical framework/approaches used to inform hematology ethics consultation support services. We conclude that ethics consult services can be a valuable resource in providing care for patients with blood disorders and are a vital resource to enhance patient care, support clinicians, and ensure that difficult choices are navigated with clarity, compassion, and integrity. |
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Journal of Clinical Oncology Valenza C, Tolaney SM In the rapidly changing field of oncology, advances in care typically start in an academic environment and then are implemented in various clinical settings with diverse patient populations. By Bridging the Gap between the highly monitored and controlled clinical trial environment and the heterogeneous, complex, and fluid settings in which patients receive care, we aim to improve understanding and raise the bar for a wider patient population, placing original research published in Journal of Clinical Oncology into a practical clinical context. |
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Journal of Clinical Oncology Kelkar AH, Abel GA, Cutler CS, Soiffer RJ Oncology clinical trials share a common goal: to help patients live longer and better. This principle is especially important in curative-intent settings such as allogeneic hematopoietic cell transplantation (HCT), where the promise is not incremental improvement but potential cure. Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS)—survival without grade 3 to 4 acute GVHD, chronic GVHD requiring systemic therapy, or relapse—has recently been adopted in many HCT trials.2,3 First proposed by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN),4 GRFS gained acceptance because it seemed to represent transplant success: disease control without major morbidity. Yet, because relapse remains the main cause of transplant failure, a composite end point that gives GVHD and relapse equal weight, treats either event as equivalent to death, and excludes other complications may not fully capture meaningful clinical benefit. Herein, we re-examine the role of GRFS as a primary end point in HCT trials and propose a pragmatic realignment of end points to match therapeutic intent while still facilitating accelerated approvals. |
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Journal of Clinical Oncology Management of Cancer During Pregnancy: ASCO Guideline Partridge AH PURPOSE: To provide guidance on the recommended management of cancer in pregnant patients. METHODS: A multidisciplinary Expert Panel convened and conducted a systematic review of the literature. RESULTS: The systematic review identified 450 eligible studies. Much of the evidence consisted of observational data, case series, and case reports. RECOMMENDATIONS: Management of cancer during pregnancy should be grounded in a values-based informed-consent process outlining maternal and fetal risks and anticipated benefits. Diagnostic evaluation should follow the as low as reasonably achievable (ALARA) principle, with timing of diagnostic studies individualized based on urgency of cancer detection, potential dangers of delay, and the balance of risks to both the pregnant patient and her embryo or fetus. Due to significant risk of harm to the developing embryo and/or fetus, systemic therapy should be deferred until the second trimester. Methotrexate, hormonal therapies, human epidermal growth factor receptor 2-targeted agents, vascular endothelial growth factor and poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and all cellular therapies are contraindicated during pregnancy, regardless of gestational age. For patients who wish to continue their pregnancy, delivery should be planned at or after 37 weeks, with the final chemotherapy dose scheduled 2-4 weeks before birth. Referral to psychosocial support services is essential to address emotional and practical challenges, reduce distress, and support shared decision making. Additional information is available at www.asco.org/survivorship-guidelines. |
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Journal of Clinical Oncology Taplin ME, Serzan MT Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at www.asco.org/genitourinary-cancer-guidelines. |
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Journal of Clinical Oncology Tung NM, Li T, DeMeo M, Vieira JP, Wulf G, Garber JE PURPOSE: Translational Breast Cancer Research Consortium 048 was a proof-of-principle trial demonstrating responses to the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in patients (pts) with metastatic breast cancer (MBC) with germline (g) PALB2 or somatic (s) BRCA mutations (sBRCAm). Here we report results from the expansion cohorts in a larger sample of pts with gPALB2m or sBRCAm. METHODS: Eligible pts had MBC of any subtype with measurable disease and a gPALB2m or sBRCAm. Pts received olaparib 300 mg twice a day until progression. The primary end point was overall response rate. Secondary end points include clinical benefit rate (CBR) at 18 weeks, progression-free survival (PFS), duration of response (DOR), and whether among sBRCAm carriers the mutant allele frequency (MAF) is significantly higher in responders than in nonresponders. RESULTS: Fifty-four pts with gPALB2m (N = 24) or sBRCAm (N = 30) were enrolled. Forty-two (78%) had estrogen receptor-positive human epidermal growth factor receptor 2-negative (HER2-) MBC, seven (13%) had triple-negative breast cancer, and five (9%) had HER2+ disease. Among pts with a gPALB2m, the overall response rate (ORR) was 75% (80% CI, 60.2 to 86.3), CBR was 83.3% (90% CI, 65.8 to 94.1), the median PFS was 9.4 months (90% CI, 8.3 to 13.1), and the median DOR was 7.0 months (90% CI, 5.6 to 10.4). Among pts with sBRCAm (15 sBRCA1 and 15 sBRCA2), the ORR was 36.7% (80% CI, 24.7 to 50), CBR was 53.3% (90% CI, 37 to 69.1), the median PFS was 5.5 months (90% CI, 2.8 to 8.3), and the median DOR was 11.2 months (90% CI, 4.4 to not reached). One additional pt had an unconfirmed partial response. Although clinically meaningful, the ORR in pts with sBRCAm did not achieve the prespecified target. Among sBRCAm carriers, the mean MAF did not differ significantly between responders (46%) and nonresponders (39%; P = .7). CONCLUSION: Olaparib is active in pts with MBC with gPALB2m and sBRCAm, significantly expanding the population of pts with breast cancer likely to benefit from PARP inhibitors beyond gBRCA1/2m carriers. |
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New England Journal of Medicine Palbociclib for Hormone-Receptor-Positive, HER2-Positive Advanced Breast Cancer Metzger O, Lynce F, Partridge AH BACKGROUND: Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies. METHODS: In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio to receive maintenance HER2-targeted and endocrine therapies with or without palbociclib. The primary end point was investigator-assessed progression-free survival. Secondary end points included the objective response, clinical benefit, safety, and overall survival. RESULTS: A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy. At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-sided P?=?0.02). Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group. CONCLUSIONS: The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.). |
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New England Journal of Medicine Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer Tolaney SM BACKGROUND: Triple-negative breast cancer is an aggressive breast cancer subtype, and there remains an unmet need to improve outcomes in patients with previously untreated, programmed death ligand 1 (PD-L1)-positive, locally advanced unresectable or metastatic triple-negative breast cancer. METHODS: In this phase 3, open-label, international trial, we randomly assigned patients in a 1:1 ratio to receive sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included overall survival, objective response (complete or partial response) and duration of response as assessed by blinded independent central review, and safety. RESULTS: A total of 443 patients were randomly assigned to receive sacituzumab govitecan plus pembrolizumab (221 patients) or chemotherapy plus pembrolizumab (222 patients). The median progression-free survival was 11.2 months (95% confidence interval [CI], 9.3 to 16.7) with sacituzumab govitecan plus pembrolizumab and 7.8 months (95% CI, 7.3 to 9.3) with chemotherapy plus pembrolizumab (hazard ratio for disease progression or death, 0.65; 95% CI, 0.51 to 0.84; two-sided P<0.001). Data for overall survival were immature. The percentage of patients with an objective response was 60% (95% CI, 53 to 66) with sacituzumab govitecan plus pembrolizumab and 53% (95% CI, 46 to 60) with chemotherapy plus pembrolizumab; among patients with a response, the median duration of response was 16.5 months (95% CI, 12.7 to 19.5) and 9.2 months (95% CI, 7.6 to 11.3), respectively. Adverse events of grade 3 or higher occurred in 71% of the patients receiving sacituzumab govitecan plus pembrolizumab and in 70% of those receiving chemotherapy plus pembrolizumab; the incidence of treatment discontinuation due to adverse events was 12% and 31%, respectively. Adverse events leading to death occurred in 3% of the patients in each group. CONCLUSIONS: Sacituzumab govitecan plus pembrolizumab led to significantly longer progression-free survival than chemotherapy plus pembrolizumab among patients with previously untreated, PD-L1-positive, advanced triple-negative breast cancer. (Funded by Gilead Sciences; ASCENT-04/KEYNOTE-D19 ClinicalTrials.gov number, NCT05382286.). |
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Proceedings of the National Academy of Sciences of the U.S.A. Traphagen NA, Wheeler E, Li R, Akhshi T, Ravindranathan R, Alfieri C, Lu F, Ahmed B, Tewari AK, Balk SP, Long H, D'Andrea AD, Qiu X, Brown M Recent clinical trials have explored the combination of androgen receptor (AR) pathway inhibitors and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors as a potential treatment for castration-resistant prostate cancer. This combination treatment is based on the premise that AR directly regulates expression of DNA repair genes, leading to synergy between PARP and AR inhibition. Despite some promising preclinical evidence, this combination therapy has shown limited efficacy in patients with homologous recombination (HR)-proficient tumors. To investigate this discrepancy between preclinical and clinical results, we profiled the effects of PARP inhibition in prostate cancer models in the presence or absence of AR inhibition. Surprisingly, AR inhibition impaired response to PARP inhibitors in castration-sensitive cells and had no effect on response in castration-resistant cells. AR inhibition also did not regulate DNA repair in either the castration-resistant or castration-sensitive setting. Instead, we find that cell cycle progression is required for response to PARP inhibition in homologous recombination-proficient prostate cancer. |
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Science Immunology Structural Variation Tunes Apoptotic Responses to Drive Immune Escape in Melanoma Kim KL, Griffin GK Immune checkpoint blockade (ICB) has transformed care for patients with melanoma, but acquired resistance to these treatments remains a major clinical challenge. In a recent study, Wu et al. used bulk and single-cell genomics tools to study genome evolution in a cohort of melanoma patients who developed acquired resistance to ICB. By analyzing paired baseline and relapse melanomas, the authors show that disease-progressive tumors recurrently amplify anti-apoptotic genes and delete pro-apoptotic genes through structural alterations such as copy-number variants (CNVs). The authors found that these CNVs do not act in isolation: Instead, tumors accumulate combinatorial CNVs regulating anti- and pro-apoptotic balance. Further examination with single-cell whole-genome sequencing revealed that ICB resistance evolves through both preexisting and subclone-private CNVs, highlighting apoptosis as a convergent mechanism selected for during ICB treatment. As the authors indicated, these CNVs collectively lower mitochondrial apoptotic priming and allow melanoma cells to overcome T cell–mediated cytotoxicity. |
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Science Translational Medicine Epigenetic Dysregulation of Metabolic Programs Mediates Liposarcoma Cell Plasticity Pimenta EM, Garza AE, Camp SY, Park J, Hoffman SE, Valderrábano L, Fu J, Bi K, Carson MT, Karam J, Titchen BM, Medjahed S, Khandekar MJ, Shannon E, Kang YJ, Coy S, Lin JR, Nag A, Thorner AR, Gibson WJ, Santagata S, Raut CP, Hornick JL, Merriam P, Solimini NL, George S, Demetri GD, Van Allen EM Sarcomas are rare cancers thought to arise from aberrant mesenchymal stem cell (MSC) differentiation. Liposarcoma (LPS) is among the most commonly diagnosed sarcomas and provides insights into dysfunctional differentiation through its well- and dedifferentiated subtypes (WDLPS and DDLPS). Despite differences in histology and clinical behavior, the molecular pathways underlying each subtype remain poorly defined, leaving patients with DDLPS reliant on empiric chemotherapies. We applied single-nucleus multiome sequencing and spatial profiling to human normal adipose, WDLPS, and DDLPS tissues and identified lineage-specific blocks in differentiation within LPS. We found that DDLPS is characterized by loss of insulin-like growth factor 1 (IGF1) signaling and activation of early mesenchymal and glucagon-like peptide-1 (GLP-1)-associated programs. IGF1 signaling loss was restricted to the DDLPS component within mixed histology tumors and correlated with poor survival in patients with LPS. In normal adipocytes, IGF1 drives differentiation through peroxisome proliferator-activated receptor gamma 2 (PPARG2). We found that DDLPS cells lack PPARG2, causing a barrier to differentiation. This defect rendered DDLPS cells unresponsive to exogenous proadipogenic signals. Restoration of PPARG2 expression alone was sufficient to reenable adipogenesis, pinpointing PPARG2 as the key molecular determinant of lineage fate. Last, IGF1 deficiency in DDLPS was associated with up-regulation of the IGF1 receptor (IGF1R), creating a selective vulnerability to IGF1R-targeted antibody-drug conjugates. In summary, we identified lineage-specific defects in DDLPS, with PPARG2 as the molecular mediator of differentiation state in LPS. More broadly, our findings demonstrate how defining lineage-specific mechanisms of tumor state can inform the development of nonchemotherapeutic treatment approaches. |
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Academic Pediatrics Understanding Fellowship Leaders' Efforts to Recruit Diverse Fellows to Pediatric Subspecialties Streater BA, Chiel L, Greenzang KA, Kesselheim JC |
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Angewandte Chemie International Edition Proteasome Cap Targeting Chimeras for Ubiquitination-Independent Targeted Protein Degradation Song C, Liu Q, Wang T, Song Y, Sigua LH, Park PM, Ficarro S, Lee S, Marto JA, Kostic M, Anderson K, Qi J |
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Annals of Surgical Oncology Evaluating the Impact of a Surgeon-Led Ductal Carcinoma in Situ Program on Endocrine Therapy Uptake Masanam MK, Kantor O, Pappas Brunco O, Faust AC, Tappan L, Harvey ME, Dudman CG, Block CC, Bychkovsky BL, Bellon JR, Mittendorf EA, King TA |
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Biochimica et Biophysica Acta – Reviews on Cancer Kufe DW |
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Blood Advances Ramirez-Gamero A, Tsakmaklis N, Hunter ZR, Guerrera ML, Guijosa A, Sarosiek S, Treon SP, Castillo JJ |
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Blood Advances Tsakmaklis N, Hunter ZR, Liu X, Kofides A, Liu S, Guerrera ML, Guijosa A, Sun H, Hatcher JM, Peachey A, Patterson CJ, Meid KE, Gustine J, Branagan AR, Sarosiek S, Castillo JJ, Treon SP |
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BMC Medicine Hantel A, Walsh TP, Gallagher E, Cronin A, Revette AC, Nava-Coulter B, Abel GA |
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Clinical Cancer Research ctDNA Dynamics and Recurrence Patterns After Organ-Sparing Trimodality Therapy for Bladder Cancer Epstein IB, Odogiyon A, Berg S, Otani Y, Mantia C, Pompa IR, Mossanen M, Wan J, Saraf A, Preston M, Ravi A, Carvalho F, Clinton T, Roberts D, Peng L, McGregor B, Bellmunt J, Kamran SC, Efstathiou JA, Miyamoto DT, Mouw KW |
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Communications Medicine Lazo de la Vega L, Comeau H, Agastra E, Sukharevsky E, Ceca E, Corson L, White J, Church AJ, Janeway KA |
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Endocrine-Related Cancer Meyerhardt JA, Chan JA |
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ESMO Open Lynce F, Valenza C, Niman SM, Ryan S, Troll E, Fanucci KA, Giordano A, Nakhlis F, Bellon J, Warren L, Block C, Schumer S, Tolaney SM, Regan MM |
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Familial Cancer Kamihara J, Fisher L, Schienda J, Vanderwall R, Khalaj A, Goler E, Hamilton KV, Garber JE, Diller LR, Rana HQ, Mack JW |
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iScience Cellular and Molecular Profiling of Collagenous Gastritis Implicates Pathogenic CD4+ T Cells Walsh MJ, Ali LR, Shen J, Kinowaki Y, Keleher CE, Chung E, Wannasai K, Ganci M, Qiang L, Thompson M, DiCarlo J, Elvin-Ivey A, Sullivan KM, Mino-Kenudson M, Dougan SK, Dougan M |
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JCI Insight Ogino A, Vajdi A, Mu XJ, Mahadevan NR, Ngo K, Booker MA, Cejas P, Okoro JJ, Xu M, Springer BF, Eschle BK, Messier CM, Wang S, Syamala S, Tamen RM, Adeni AE, Chambers ES, Thai T, Christensen CL, Xu C, Lizotte PH, Oxnard GR, Long HW, Gokhale PC, Paweletz CP, Sholl LM, Oser MG, Barbie DA, Tolstorukov MY, Jänne PA |
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Journal for ImmunoTherapy of Cancer Viray H, M Mantia C, Jegede OA, Choueiri TK, McDermott DF, Regan MM |
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Journal of Medicinal Chemistry Hatcher JM, Liu S, Kofides A, Canning A, Pizzarella D, Liu X, Tsakmaklis N, Guerrera M, Patterson C, Guijosa A, Gokhale P, Hunter Z, Sarosiek S, Castillo J, Wang J, Buhrlage SJ, Treon SP |
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Journal of Medicinal Chemistry Sharafi M, Teh WP, Green J, Charifson PS, Wang J, Lye M, Liu X, Varca AC, Dawson C, Steuber C, Smith J, Girardi NM, Magin RS, Marto JA, Namchuk MN, Buhrlage SJ |
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Journal of Nuclear Medicine LASER: A Phase 2 Trial of 177Lu-PSMA-617 as Systemic Therapy for RCC Hazut Krauthammer S, Xie W, LaBrecque N, Arsenault L, Kabarame L, Shah H, Berg S, McGregor B, Serzan M, Xu W, Viswanathan SR, Wei XX, Choueiri TK, Jacene H, Ravi P |
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Journal of Pain and Symptom Management Opportunities for Palliative Care in Long-Term Acute Care: A Concurrent Mixed-Methods Study Walker KH, Lambert V, Liu A, Rubin EB, Chua IS, Ufere NN, Reich AJ, Tulsky JA, Lakin JR |
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Leukemia and Lymphoma Sarosiek S, Castillo JJ, Hunter ZR, Branagan AR, Treon SP |
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Molecular Cancer Therapeutics Tesar B, Bird GH, Godes M, Wu R, Filbin MG, Walensky LD |
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Nature Nanotechnology Resolving DNA Origami Structural Integrity and Pharmacokinetics in Vivo Wang Y, Wu YC, Zhu J, Jia Y, Wu MR |
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NPJ Vaccines Khan RA, Chen J, Donius L, Reinherz EL, Kim M |
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Nucleic Acids Research Darbeheshti F, Zeggar HR, Salmani H, Ghazali S, Liu R, Adalsteinsson VA, Makrigiorgos GM |
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Pediatric Blood and Cancer Kao PC, Payne B, London WB |
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Pilot and Feasibility Studies Yi-Frazier JP, Rosenberg AR |
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Transplantation and Cellular Therapy Keane EP, Adri FN, Larizza IS, Monahan JA, Song MT, Boardman AC, Schaefer DA, Wu JH, Conway S, Gudenkauf LM, Amonoo HL |