Welcome to Dana-Farber's Research News
March 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 February 16 - 28.
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 What's in a Name? HLH/Hyperinflammatory Syndromes Nikiforow S, Berliner N In this issue of Blood, Rocco et al report insights into the role of interferon gamma (IFN-?) in mortality associated with adult hemophagocytic lymphohistiocytosis (HLH). In a retrospective study of 171 clinically annotated patients older than 15 years with hyperinflammatory syndromes, 126 patients met the criteria for HLH (based on 4/8 HLH-2004 criteria or an HScore ?169). In addition to the standard laboratory parameters, the authors added measurement of C-X-C-motif ligand-9 (CXCL9), an accepted surrogate marker of IFN-?–driven inflammation and an established mediator of the hyperinflammation associated with primary HLH in associated animal models. |
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Cell Giant DNA Viruses Encode a Hallmark Translation Initiation Complex of Eukaryotic Life Fels JM, Hill AB, Han R, Garcia JM, Kranzusch PJ, Lee ASY In contrast to living organisms, viruses were long thought to lack protein synthesis machinery and instead depend on host factors to translate viral transcripts. Here, we discover that giant DNA viruses encode a distinct and functional IF4F translation-initiation complex to drive protein synthesis, thereby blurring the line between cellular and acellular biology. During infection, eukaryotic IF4F on host ribosomes is replaced by an essential viral IF4F that regulates viral translation, virion formation, and replication plasticity during altered host states. Structural dissection of viral IF4F reveals that the mRNA cap-binding subunit mediates exclusive interactions with viral mRNAs, constituting a molecular switch from translating host to viral proteins. Thus, our study establishes that viruses express a eukaryotic translation-initiation complex for protein synthesis, illuminating a series of evolutionary innovations in a core process of life. |
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JAMA A Scalable Model to Improve Cancer Care for Older Adults-Lo-Fi, High Impact Wright AA, Enzinger AC Individuals aged 70 years and older account for more than 40% of patients with cancer in the US and 25% of those with incident cancers. Yet older adults have been largely neglected by cancer research and care improvement efforts. Less than 3% of older patients with cancer are enrolled in oncology clinical trials, and the landscape of treatments received by older adults is not well understood. Comorbid conditions, frailty, and resource limitations can necessitate modifications to cancer treatments and render older patients more vulnerable to complications. Moreover, many may be ineligible for or choose to forgo anticancer therapy and therefore see oncology practitioners infrequently – despite experiencing symptoms and conditions that require ongoing management. These complexities beg for scalable strategies to monitor and support older adults with cancer. |
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JAMA Aizer AA, Shin KY, Catalano PJ, Ricca I, Johnson M, Benham G, Spicer B, Mann E, Nosker J, Parsons MW, Mendu ML, Shi DD, Lamba N, Wen PY, Haas-Kogan DA, Rahman R, Tanguturi S IMPORTANCE: Brain metastases are common in patients with cancer, and radiation is often used for management. Among patients with more than 4 brain metastases, the effects of stereotactic radiation targeting only individual tumors, compared with whole brain radiation with hippocampal avoidance, which radiates both tumors and normal brain, remain unknown. OBJECTIVE: To determine whether stereotactic radiation improves symptom severity and interference with daily functioning, compared with whole brain radiation with hippocampal avoidance. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, open-label, randomized clinical trial conducted at 4 United States-based centers. Eligible patients had 5 to 20 brain metastases and no prior brain-directed radiation. Enrollment occurred between April 11, 2017, and May 17, 2024 (final follow-up, March 18, 2025). INTERVENTION: Stereotactic radiation, compared with whole brain radiation with hippocampal avoidance. MAIN OUTCOMES AND MEASURES: Mean weighted patient-reported symptom severity and interference score change over 6 months postbaseline relative to baseline using the MD Anderson Symptom Inventory-Brain Tumor instrument (scale, 0-10; score change range, -10 to 10; -10?=?best). A clinically meaningful ? was defined as 0.98. RESULTS: Of 196 randomized patients (mean age, 61 years; 129 [66%] female; 176 [90%] White; median number of brain metastases, 14 [IQR, 11-18]; 49 [25%] with prior neurosurgical resection), 83 (42%) completed the 6-month assessment. For the primary outcome, between baseline and postbaseline assessments through the 6-month follow-up, stereotactic radiation changed the weighted composite MD Anderson Symptom Inventory-Brain Tumor score from 2.69 to 2.37 (mean change, -0.32) and hippocampal-avoidance whole brain radiation changed the score from 2.29 to 3.03 (mean change, 0.74) (mean difference, -1.06 [95% CI, -1.54 to -0.58]; P?<?.001). Related grade 3-5 adverse events occurred in 12 patients (12%) in the stereotactic radiation group and 13 patients (13%) in the hippocampal-avoidance whole brain radiation group; grade 1-3 fatigue was most frequent (27 [28%] vs 43 [44%], respectively). CONCLUSIONS AND RELEVANCE: In patients with 5 to 20 brain metastases, these findings support stereotactic radiation over hippocampal-avoidance whole brain radiation to improve symptoms and interference with daily functioning, key components of quality of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03075072 |
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JAMA Oncology Valenza C, Burstein HJ Patients with advanced breast cancer have a growing armamentarium of treatment options, and nearly all will receive multiple lines of treatment. On average, response rates and median times to progression are higher in first-line than in second-line, and in second-line than in third-line, and so forth, though clinical experience shows that outcomes for individual patients are quite variable. Many drugs are approved based on initial studies of treatment-resistant cancer, and then are studied again to see if utilization earlier in the course of advanced cancer would also be effective. As more treatment options enter routine clinical practice, there are important, practical questions about the optimal sequencing of agents and questions about when in the sequence of therapy drugs should be deployed to maximal utility. There are potential clinical benefits to earlier utilization of active, important agents. Drugs might be more efficacious in an earlier line of therapy owing to tumor biology or therapeutic resistance or might have salutary clinical outcomes such as preserving quality of life for longer arcs of time, delaying the time to initiation of agents that have more adverse events, or improving overall survival (OS). There are also commercial implications to the timing of drug utilization, as treatment durations are typically longer in earlier lines of treatment. Finally, there are concerns that delaying initiation of an important drug might forfeit the opportunity for treatment if the patient cannot receive additional lines of therapy. Yet despite these compelling reasons to study the optimal sequencing of treatments, few clinical trials are designed to address such questions once drugs have secured regulatory approval. |
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Journal of Clinical Oncology Davids MS Over the past decade, the treatment landscape for chronic lymphocytic leukemia (CLL) has evolved rapidly with the approval of three oral, covalent Bruton tyrosine kinase inhibitors (cBTKi)—ibrutinib, acalabrutinib, and zanubrutinib—which were all previously shown to lead to superior progression-free survival (PFS; and in some cases overall survival [OS]) compared with chemoimmunotherapy when given as continuous therapies in the treatment-naïve (TN) setting. Time-limited targeted regimens incorporating the oral B-cell leukemia/lymphoma-2 inhibitor (BCL-2i) venetoclax as a backbone, combined with anti-CD20 monoclonal antibodies such as obinutuzumab, cBTKi, or all three mechanisms together, have also now become standard frontline treatment options. |
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Journal of Clinical Oncology Valenza C, Zheng Y, Kirkner GJ, Dibble KE, Regan MM, Partridge AH PURPOSE: To evaluate the clinical benefit of extended endocrine therapy (eET) after 5 years of adjuvant treatment with luteinizing hormone-releasing hormone agonists (LHRHa) in premenopausal women with node-positive, hormone receptor-positive early breast cancer (eBC). METHODS: We conducted a cohort study analysis on two prospectively collected data sets (the Young Women's Breast Cancer Study and IEO Breast Cancer Cohort). Eligible patients were diagnosed with eBC at age ?40 years (between 2005 and 2016), had node-positive, hormone receptor-positive disease, and remained premenopausal after 5 years of adjuvant LHRHa with no evidence of recurrence. The primary end point was invasive breast cancer-free survival (IBCFS), calculated from the sixth year after the initiation of adjuvant endocrine therapy (ET; study baseline), and adjusted through the propensity score (PS) weighting analysis. RESULTS: A total of 501 patients were included in the analysis: 287 received eET for a median duration of 3.7 years (IQR, 2.3-5.0), including 48% tamoxifen monotherapy and 52% LHRHa plus tamoxifen or aromatase inhibitor. After a median follow-up of 7.3 years from the study baseline, the PS weighted IBCFS rates at 5 years were 85% in the eET group and 78% in the non-eET group (hazard ratio [HR], 0.63 [95% CI, 0.44 to 0.89]; P = .0135). The PS weighted distant recurrence-free survival rates at 5 years were 91% and 83% in the eET and non-eET group, respectively (cause-specific HR, 0.49 [95% CI, 0.31 to 0.79]). In both groups, bone fractures and major cardiovascular events were reported in 1% of patients. CONCLUSION: In this cohort study analysis, extending ET in premenopausal patients with node-positive eBC after 5 years of LHRHa treatment was associated with a clinically meaningful reduction in both invasive and distant breast cancer recurrences. |
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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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Lancet Oncology Towards Response-Adapted Neoadjuvant Breast Cancer Treatment Nader-Marta G, Mayer EL The therapeutic landscape of early-stage HER2-positive breast cancer has been transformed over the past two decades. The introduction of HER2-directed therapy, including the antibody trastuzumab, has fundamentally altered the natural history of this disease, converting an aggressive breast cancer subtype associated with poor outcomes into one with high rates of pathological complete response and excellent long-term survival. These gains were initially achieved using intensive multi-agent regimens incorporating HER2-directed therapies with anthracyclines, taxanes, and platinum chemotherapy in both the adjuvant and neoadjuvant settings. However, with greater understanding of how tumour heterogeneity affects treatment sensitivity, uniform application of intensive regimens might result in overtreatment for a substantial subset of patients who could achieve excellent clinical outcomes with a less burdensome approach. In response, contemporary research has focused on tailoring systemic therapy while preserving treatment efficacy, including a reduction in chemotherapy intensity or duration and, in the preoperative setting, response-adapted approaches informed by early indicators of treatment sensitivity. |
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Nature Nucleotide Signals Coordinate Activation and Inhibition of Bacterial Immunity Yamaguchi S, Fernandez SG, Wassarman DR, Kranzusch PJ The cellular nucleotide pool is a major focal point of the host immune response to viral infection. Immune effector proteins that disrupt the nucleotide pool enable animal and bacterial cells to broadly restrict diverse viruses, but reduced nucleotide availability induces cellular toxicity and can limit host fitness1-5. Here we identify Clover, a bacterial anti-phage defence system that overcomes this trade-off by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). Analysis of phage restriction by Clover in cells and reconstitution of enzymatic function in vitro demonstrate that CloA is a dGTPase that responds to viral enzymes that increase cellular levels of dTTP. To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal, p3diT (5'-triphosphothymidyl-3'5'-thymidine), that binds to CloA and suppresses activation. Cryo-electron microscopy structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function. Our results define how nucleotide signals coordinate both activation and inhibition of antiviral immunity and explain how cells balance defence and immune-mediated toxicity. |
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Nature Communications Venkadakrishnan VB, Yamada Y, Booker MA, Tolstorukov MY, Beltran H Prostate cancer lineage plasticity is associated with changes in DNA methylation and enhancer of zeste homolog 2 (EZH2) activity. How these epigenetic programs functionally interact to modulate transcriptional reprogramming in neuroendocrine prostate cancer (NEPC) is not well understood. In this study, we demonstrate that hypomethylated regions of DNA preferentially accumulate the repressive mark, H3K27me3. We established an NEPC mouse model with deletion of Ezh2 in the background of Pten and Rb1 loss plus human MYCN overexpression. Deletion or pharmacological inhibition of EZH2 in NEPC murine or patient-derived models leads to a genome-wide rewiring of DNA methylation, characterized by hypomethylation and upregulation of neuroendocrine-lineage genes along with hypermethylation and repression of polycomb repressive complex 2 (PRC2) targets. On the other hand, deletion of DNA methyltransferase 1 (DNMT1) results in significant changes in H3K27me3 distribution, particularly affecting bivalent promoters bearing both H3K27me3 and active H3K4me3 marks. In NEPC models, neuroendocrine-lineage genes are repressed upon DNMT1 deletion associated with increased H3K27me3. Conversely, in prostate adenocarcinoma models, DNMT1 deletion leads to de-repression of neuroendocrine lineage genes with a loss of H3K27me3 marks. Our findings reveal a functional interplay between two repressive epigenetic machineries that mediates lineage plasticity in prostate cancer. |
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Proceedings of the National Academy of Sciences of the U.S.A. Yan P, Bui T, Rojas Jimenez E, Kuang Y, Xu S, CP Paweletz , McAllister SS, Polyak K Aging is a major risk factor for breast cancer, yet how it shapes tumor development, molecular phenotype, and immune evasion remains incompletely understood. Deciphering how aging influences cancer evolution is critical for improving risk assessment, prevention, and treatment. Here, using a N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model that recapitulates key features of human breast cancer, we integrated bulk and single-cell transcriptomics, whole-exome sequencing, and histopathological analysis to dissect age-associated differences in mammary tumorigenesis. We found that the age at NMU exposure critically influences tumor incidence, mutational burden, molecular subtype, and the tumor immune microenvironment. Tumors arising in aged rats originated from aging luminal progenitor-like cells, exhibited increased genomic instability, reduced immune cell infiltration, and impaired antigen presentation linked to loss of heterozygosity at chromosome (Chr) 20p. The age-associated epithelial and immune changes we identified were conserved in human breast cancers, where the loss of the homologous Chr 6p region correlated with reduced lymphocyte infiltration and shorter relapse-free survival. These findings reveal that aging profoundly affects tumor-initiating cell populations and promotes immune evasion through chromosomal instability-driven defects in antigen presentation. Our work provides a molecular basis for understanding disease onset and progression that may impact efficacy of immunotherapy in older breast cancer patients. |
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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 Masanam MK, Kantor O, Brunco OP, Faust AC, Tappan L, Harvey ME, Dudman CG, Block CC, Bychkovsky BL, Bellon JR, Mittendorf EA, King TA |
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BioDrugs Antibody-Drug Conjugates in Gynecologic Oncology: Advances, Challenges, and Future Directions Lantsman T, Matulonis UA |
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Blood Advances Murdock HM, Kim HT, Maurer K, Kelkar A, Shapiro RM, Gooptu M, Romee R, Nageshwar PK, Garrity HM, Shimony S, Luskin MR, Winer ES, Vedula RS, Chen EC, Volpe V, Garcia JS, Wadleigh M, DeAngelo DJ, Stone RM, Wu CJ, Cutler CS, Koreth J, Ritz J, Antin JH, Ho VT, Nikiforow S, Soiffer RJ |
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BMJ Supportive and Palliative Care Beaussant Y, Sager Z, Kristan I, Ljuslin M, Mazzola E, Nigam K, Rinaldi AD, Schaefer KG, Sholevar R, Summer L, Tulsky JA |
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Cancer Research Communications Diagnostic Outcomes Among Patients with Positive Multi-Cancer Early Detection Test Results O'Donnell EK, Kauffman TL, Asnis S, Kelly VA, Matthews E, Kartsounis M, Dharaneeswaran H, Beckwith JB, Bennett C, Marto M, Parmigiani G, Rebbeck TR, Ghobrial IM, Syngal S, Marinac CR |
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Cell Chemical Biology Metabolic Control of Innate Immune Activation in TET2-Mutant Clonal Hematopoiesis Kim PG, Hergott CB, Miller AP, Deik A, Boileau M, Bullock K, Pierce KA, Choy AH, Shin W, McConkey M, Loke J, Ryback BA, Trinh MN, Rutter JC, Yue H, Yoon H, Park P, Roy Burman SS, Vander Heiden MG, Fischer ES, Armstrong SA, Clish C, Ebert BL |
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Cell Chemical Biology Systematic Cysteine Scanning Identifies a Druggable Pocket in Oncogenic KRAS van Tienen LM, Bayoumi S, Muneeruddin K, Leymarie N, Shekhar M, Mueller M, Li R, Chilukuri H, Kornfilt DJP, Atack TC, Kesar D, Bian Y, Shaw KL, Sellers WR |
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Cell Reports Abou Alaiwi S, Adib E, Zhang Z, Spisak S, Cordeiro P, El Zarif T, Sztupinszki ZM, Nassar AH, Seo JH, Campbell R, Steinharter JA, Pomerantz M, Signoretti S, Szallasi Z, Gusev A, Baca SC, Choueiri TK, Freedman ML |
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Current Oncology Reports Integrative Oncology for Biochemical Recurrence of Epithelial Ovarian Cancer Berman T |
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European Urology Steiner C, Ascione L, Liu X, Choueiri TK, Xu W |
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European Urology Oncology Expanding Risk-Adapted Early Detection of Prostate Cancer: A Call to Action for Men at High Risk Klett MK, Kibel A, Rana HQ, Serzan M, Morgans AK |
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Genes and Development Wang Y, Manokaran C, Zou Y, Chen J, Gu H, Liu D, Zhao JJ, Roberts TM |
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Hepatology Communications Jin Q, Tayob N |
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JCO Oncology Practice Wilson RL, Giobbie-Hurder A, Ligibel JA, Dieli-Conwright CM |
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Journal of Adolescent and Young Adult Oncology Adaptive Psychosocial Outcomes in Cancer Predisposition Syndromes: A Scoping Review Hanania JW, Tsang KK, Rotman C |
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Journal of Cancer Survivorship Dibble KE, Knelson LP, Morgans AK, Partridge AH, Nekhlyudov L |
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Journal of Health Communication Kikut-Stein A, Jesch E, Dhawan D, Viswanath K |
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Journal for ImmunoTherapy of Cancer Moravej H, Rakhshandehroo T, Khan RMM, Rivet VM, Marcandalli E, Mantri SR, Taklifi P, Lee UJ, Louis BBV, Munaretto LA, Farkash Z, Berland L, Gabr Z, Wolff AN, Kowalewski A, Allen HH, Nili A, Baral J, Mercadante D, Fulciniti M, Jacobson CA, Sperling AS, Nadeem O, Nia HT, Munshi NC, Rashidian M |
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Journal of the European Academy of Dermatology and Venereology O'Connell KA, Murad F, Mossanen M, Clinton TN, Schmults CD |
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Molecular Cancer Research Adib E, Hanlon T, Bou Farhat E, Tang Y, Seo JH, Losko M, Zhang Z, Hirsch MS, Gusev A, Mouw KW, Choueiri TK, Kwiatkowski DJ, Freedman M |
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Neurology Baselga-Garriga C, Purohit S, Lamba N, Catalano PJ, Haas-Kogan DA, Tobochnik S, Bubrick EJ, Marciscano AE, Khandekar MJ, Rahman RM, Tanguturi SK, Bi WL, Wen PY, Aizer AA |
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NPJ Breast Cancer Sammons SL, Kuntz TM, DiLullo M, Morgan XC, Martin A, Hughes ME, Rahman T, Ogayo ER, Ryan S, Waks AG, Schlam I, Ligibel J, Lin NU, Garrido-Castro AC, Mittendorf EA, Tolaney SM |
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NPJ Precision Oncology Tumor Genomics in Patients Younger than 40 Years of Age with Metastatic Breast Cancer Brantley KD, Kodali A, Kirkner GJ, Hughes ME, Li Y, Files J, Strauss S, Feeney AM, Mohammed-Abreu A, Bychkovsky B, Tannenbaum C, Loucks M, LeStage BK, King T, Johnson BE, Sholl L, Dillon D, Tolaney SM, Cherniack AD, Partridge AH, Lin NU, Garrido-Castro AC |
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Oncologist Impact of Immune Checkpoint Inhibition on Ovarian Reserve Buchbinder EI, Song Z, Cohen JV, Lee SJ, Smith KK, Manos M, Dougan M |
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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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Science Advances Camp SY, He MX, Cuoco MS, Garza AE, Xirenayi S, Bakouny Z, Saad E, El Masri J, Pimenta E, Meli K, Labaki C, Titchen BM, Kang YJ, Horst J, Trowbridge R, Shannon E, Helvie K, Thorner AR, Vigneau S, Mayorga A, Kodali J, Lachmayr H, Bemus M, Park J, Choueiri TK, Bi K, Van Allen EM |