Dana-Farber Research News 11.01.2026
Welcome to Dana-Farber's Research News
November 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 October 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 Autologous T-Cell Antigen Coupler Targeting HER2 (TAC01-HER2) in Advanced or Metastatic Solid Tumors Weiss JA, Schlechter BL BACKGROUND: The T-cell antigen coupler (TAC) is a novel genetically engineered receptor that recruits the native T-cell receptor upon recognition of an antigen. The downstream activation of TAC T cells has been effective against tumors in preclinical models and is safer than chimeric antigen receptor T cells. Human epidermal growth factor receptor 2 (HER2) is a validated biomarker for cancer-targeted therapy, but cell therapy approaches have been met with unmanageable toxicity. PATIENTS AND METHODS: We designed a phase I clinical trial of TAC01-HER2, an autologous T-cell product that targets HER2, in patients with HER2-positive advanced solid tumors. The trial had a dose-escalation phase and dose expansion at the recommended phase II dose (RP2D). RESULTS: A total of 23 patients with HER2-positive solid tumors were enrolled in this study. The most common treatment-related adverse events (AEs) were cytokine release syndrome (n = 14, 60.9%), anemia (n = 5, 21.7%), and increased alanine aminotransferase (n = 5, 21.7%). The RP2D was 6-8 × 106 cells/kg. No treatment-related deaths or AEs leading to study discontinuation were reported. Two of nine patients with gastric and gastroesophageal junction (GEJ) cancers had partial responses (PRs), and the disease control rate (stable disease or PR) was 61.1% in the 18 patients with evaluable tumors. The median progression-free survival was 2.6 months (range 0.8-12.4), and the overall survival rate at 6 months was 57.9% (95% confidence interval 36.3% to 76.9%). Persistence of TAC T cells in peripheral blood was observed in all patients until at least day 29 after the first infusion. CONCLUSION: We demonstrated that treatment with TAC T cells was safe, feasible, and well-tolerated. TAC01-HER2 showed manageable toxicity and early efficacy for patients with HER2-positive gastric, GEJ, or esophageal adenocarcinoma who have undergone extensive previous treatments. These results suggest that TAC may offer a promising approach to control T-cell activity through cellular therapy. |
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Annals of Oncology Burstein HJ, Gelber RD, Goldhirsch A, Regan MM BACKGROUND: The Suppression of Ovarian Function Trial (SOFT) found adding ovarian function suppression (OFS) to tamoxifen (T) reduced breast cancer recurrence, and exemestane (E)+OFS further reduced recurrence. A combined analysis of SOFT and TEXT showed a significant reduction in distant recurrence with E+OFS versus T+OFS. We now report final 15-year outcomes. PATIENTS AND METHODS: Premenopausal women with hormone receptor-positive early breast cancer were enrolled, with 3047 in SOFT and 2660 in TEXT intention-to-treat populations. SOFT randomized to 5 years of T versus T+OFS versus E+OFS. TEXT randomized to 5 years of T+OFS versus E+OFS. Chemotherapy was optional, before SOFT entry with subsequent premenopausal oestradiol or concurrent with OFS in TEXT. Endpoints included disease-free survival, breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI), and overall survival (OS). Additionally, 15-year Kaplan-Meier estimates, hazard ratios (HRs), and 95% confidence intervals (CIs) are reported. RESULTS: In SOFT, escalating endocrine therapy (ET) continued to reduce recurrence with 15-year BCFI of 78.6% for E+OFS, 75.7% for T+OFS, and 72.1% for T (T+OFS versus T: HR 0.82, 95% CI, 0.69-0.98, P = 0.03). In the SOFT no-chemotherapy cohort, OFS reduced breast cancer events at 15 years, while DRFI and OS remained high regardless of ET assignment. After prior chemotherapy for HER2-negative tumors (n = 1257), the 15-year OS rate in SOFT was 81.0% with E+OFS, 77.1% with T+OFS and 76.8% with tamoxifen alone. In women under age 35 years with HER2-negative tumors (n = 241), the 15-year OS rate was 82.5% with E+OFS, 77.9% with T+OFS, and 68.1% with tamoxifen. In combined SOFT and TEXT analysis, among those with HER2-negative tumors (n = 4035), E+OFS versus T+OFS reduced distant recurrence (HR 0.75, 95% CI 0.63-0.90), with a smaller reduction in deaths (HR 0.89, 95% CI 0.74-1.06), with absolute survival benefits largest with high-risk features, particularly young age or high-grade tumors. CONCLUSION: Meaningful OS benefit in hormone receptor-positive, HER2-negative breast cancer from adjuvant exemestane and/or OFS compared with tamoxifen alone is limited to high-risk premenopausal subgroups. Tamoxifen-based ET may not result in optimal outcomes in premenopausal high-grade HER2-negative tumors. ClinicalTrials.gov identifier: NCT05016947. |
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Annals of Oncology Garrido-Castro AC, Kim SE, Li T, Desrosiers J, O'Connor T, Sinclair N, Augdahl G, Wrabel E, DiLullo M, Rahman T, Patel A, Hughes ME, Baginska J, Lange PB, O'Meara T, Keenan TE, Koca B, Kurnia PT, Perry AN, Gomez Tejeda Zanudo J, Dillon DA, Lin NU, Burstein HJ, Mittendorf EA, Jeselsohn R, Tayob N, Tolaney SM BACKGROUND: Sacituzumab govitecan (SG), a TROP2-directed topoisomerase I-inhibitor (TOP1i) antibody-drug conjugate, is approved for chemorefractory hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). To evaluate if pembrolizumab (programmed cell death protein 1 inhibitor) enhances the activity of SG, we conducted a randomized phase II study comparing SG with or without pembrolizumab in HR-positive/HER2-negative MBC. MATERIALS AND METHODS: Patients with HR-positive/HER2-negative MBC pretreated with endocrine therapy and 0-1 chemotherapy regimens for MBC (no prior TOP1i) were randomly assigned 1:1 to receive SG plus pembrolizumab or SG. Primary endpoint was progression-free survival (PFS). Key secondary endpoints included PFS in the programmed death-ligand 1 (PD-L1)-positive population (pharmDx 22C3 combined positive score ?1), overall survival (OS), objective response rate (ORR), and toxicity. Baseline tumor tissue and plasma samples were collected for correlative analyses. RESULTS: Between March 2021 and January 2024, 104 patients started treatment; 47% (49) had not received chemotherapy for MBC. At 15.5-month median follow-up, SG plus pembrolizumab did not significantly improve PFS compared with SG [8.4 versus 6.7 months; hazard ratio (HzR) 0.76, 95% confidence interval (CI) 0.48-1.19, P = 0.12]. Median OS was 20.0 versus 18.0 months (P = 0.18); ORR was 28.8% versus 19.2% (P = 0.36). In the PD-L1-positive population (44%; 39/88 with tissue), median PFS (11.1 versus 5.6 months; HzR 0.51, 95% CI 0.24-1.12, P = 0.09) and OS (18.5 versus 12.5 months; HzR 0.59, 95% CI 0.18-1.98, P = 0.39) numerically increased with the combination. Most frequent grade ?2 adverse events were neutropenia, alopecia, fatigue, anemia, nausea, leukopenia, and diarrhea. Neither TROP2 expression by immunohistochemistry, immunofluorescence, or plasma epigenome-based analysis, or tumor-infiltrating lymphocytes were associated with outcomes. Higher circulating tumor DNA fraction and PIK3CA mutations were associated with worse PFS. Plasma epigenome-pathway analysis suggested that high cell cycle or epithelial-mesenchymal transition activation may confer sensitivity or resistance to SG, respectively. CONCLUSION: Addition of pembrolizumab to SG did not significantly improve outcomes in HR-positive/HER2-negative MBC unselected by PD-L1. In the PD-L1-positive population, the trend in PFS and OS favoring SG plus pembrolizumab warrants further investigation in larger randomized trials. |
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Annals of Oncology Thymic Radiation Is Associated with Worse Outcomes in Patients with NSCLC Prudente V, Bernatz S, Pai S, Pecci F, Garbo E, Bressem K, Guthier CV, Warrington A, Tonneau M, Ciausu C, Yu S, Thompson L, Mannarino E, Nürnberg L, Kehayias CE, Ricciuti B, Mak RH, Aerts HJWL BACKGROUND: Emerging evidence indicates the functional importance of the thymus in adult health and may influence oncological outcomes, yet current radiotherapy (RT) practice does not consider the thymus as an organ of interest. Because RT may incidentally expose the thymus to radiation, we hypothesized that thymic radiation dose is negatively associated with major clinical outcomes. PATIENTS AND METHODS: This multicohort analysis included 1107 patients with non-small-cell lung cancer (NSCLC), including the phase III RTOG-0617 trial (n = 460) and two independent real-world cohorts of patients treated with chemoradiotherapy alone (n = 422; HARVARD-CRT) or in combination with consolidation immunotherapy (n = 225; HARVARD-DURVA). We quantified thymic function using a deep learning system that assessed thymic radiographic characteristics as a proxy for thymic function. Mean thymic dose (MTD) was used to measure thymic radiation exposure. RESULTS: Incidental thymic irradiation was associated with increased risk of distant metastases after confounding adjustments. Concretely, a 1-Gy increase in MTD was associated with an increased distant metastasis risk of 1.57%-4.21% [RTOG-0617: adjusted hazard ratio (aHR) 1.29, P = 0.0028; HARVARD-CRT: aHR 1.33, P = 0.011; HARVARD-DURVA: aHR 1.95, P = 0.007]. In thymic health (TH)-stratified analysis, patients with preserved TH before RT appeared to be at particularly greater risk, whereas no associations emerged in patients with impaired TH. One-year follow-up imaging demonstrated dose-dependent declines in TH and lower circulating lymphocyte counts, consistent with a possible biological link between thymic irradiation and loss of immune competence. An exploratory feasibility study suggested that reoptimizing RT planning for thymic sparing can be achieved without compromising tumor coverage or cardiopulmonary constraints. CONCLUSIONS: Thymic radiation exposure was independently associated with higher risks of metastasis and death in patients with NSCLC, especially in those with preserved thymic function. These findings raise awareness toward considering the thymus as an organ of interest in RT and suggest that thymus-sparing strategies may help preserve immune health and improve patient outcomes. |
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Blood Crombie JL, Redd R, Phinney C, Forsyth M, Mai J, Re S, LaCasce AS, Odejide OO, Parry EM, Qualls DA, Ryan CE, Merryman RW, Fisher DC, Kim AI, Jacobson CA, Jacobsen ED, Brown JR, Ahn IE, Davids MS, von Keudell G, Armand P In this phase II trial, we evaluated the addition of the CD3xCD20 bispecific antibody, glofitamab (glofit) to polatuzumab, rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and an international prognostic index (IPI) ³ 2. Patients received two cycles of pola-R-CHP (one cycle of R-CHOP allowed). Glofitamab was added to pola-R-CHP during cycles 3 through 6 and used as monotherapy for cycles 7 and 8. The primary objective was the best complete response (CR) rate. A total of 41 patients enrolled. The median age was 61 years (range 35-86), and 59% were male. IPI scores were 2 (39%), 3 (41%), and 4 (20%), and 86% of patients had stage III/IV disease. Most patients had DLBCL, NOS (78%) and 12% had high grade B-cell lymphoma with translocations in MYC and BCL-2 and/or BCL-6. The best CR rate was 95% (39/41) (95% CI: 83-99) and both patients with a partial response at the end of therapy converted to CR without intervention. With a median follow-up of 23.9 months, the median progression-free survival (PFS) has not been reached and the 24-month PFS was 95% (95% CI: 89-100). Four (10%) patients developed cytokine release syndrome (CRS) (all grade 1), and no immune effector cell-associated neurotoxicity syndrome (ICANS) was reported. Glofit-pola-R-CHP resulted in high rates of CR and preliminary evidence of durable responses and the schedule, with delayed incorporation of glofit, resulted in low rates of CRS and no neurotoxicity. These data support further evaluation of this regimen. NCT05800366. |
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Blood Gagelmann N, Reilly CR, Sasi A, Hebert K, Cutler CS, Soiffer RJ, Lindsley RC Germline DDX41 variants are a recognized cause of adult myelodysplastic neoplasms (MDS), characterized by distinct biological features and favorable prognosis. The independent effect of DDX41 status on outcomes after allogeneic transplantation, the role of conditioning intensity, and treatment-related toxicity risk remain unresolved. To address this gap, we analyzed 1,514 patients with MDS undergoing transplantation prior to routine DDX41 testing alongside a wild-type comparator, providing an unbiased benchmark for this molecular subgroup. Forty-nine patients (3.2%) carried pathogenic/likely pathogenic (P/LP) germline DDX41 variants; 19 (39%) had an additional somatic DDX41 mutation, most commonly p.R525H. P/LP DDX41 cases were older (median 63 vs 59 years) and showed lower IPSS-M risk with absent TP53 mutations (0% vs 21%). In terms of outcome, 2-year relapse incidence was significantly lower in P/LP DDX41 (17% vs 34%, p=0.01). In multivariable analysis, the presence of a DDX41 P/LP variant independently associated with lower risk of relapse (hazard ratio 0.43, 95% CI 0.21-0.88; p=0.02), concentrated in the reduced-intensity/nonmyeloablative stratum. Adjusted models showed significantly improved disease-free survival (DFS) for P/LP DDX41 (hazard ratio 0.62, 95% CI 0.41-0.95; p=0.03) and no significant association with non-relapse mortality (NRM) or graft-versus-host disease (GVHD). In summary, these findings identify DDX41-associated MDS as a transplant subgroup with superior DFS regardless of conditioning intensity driven by reduced relapse risk and lack of excess NRM and GVHD supporting incorporation of germline DDX41 status into transplant planning. |
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Blood Liso-Cel Delivers: Is the Debate Over for 3L FL? Ruiz-Esteves KN, Jacobson CA In this issue of Blood, Ahmed et al report the 3-year-follow-up of the TRANSCEND FL trial, offering compelling evidence for the long-term efficacy and safety of lisocabtagene maraleucel (liso-cel) in relapsed/refractory follicular lymphoma (FL). These updated results build on the initial published data that led to the accelerated US Food and Drug Administration approval of liso-cel in the third-line (3L) setting for FL, based on high efficacy outcomes and a relatively favorable safety profile when compared with other chimeric antigen receptor (CAR) T-cell products. |
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Blood T Cells Targeting Immunoglobulin in Myeloma: A Way Forward? Avigan DE In this issue of Blood, parallel studies by Douvlataniotis et al and Meeuwsen et al explore a strategy of adoptive T-cell therapy using T-cell receptors (TCRs) targeting peptides derived from the immunoglobulin heavy chain (IgH) in myeloma cells. Uniform and consistent expression of the IgH by malignant plasma cells results in the presentation of endogenously generated peptides for immune targeting that is independent of surface expression. |
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Cell Stem Cell Klatt D, Mucci A, Liu B, Peschers M, Schiroli G, Manis J, Armant M, Scadden DT, Pellin D, Williams DA, Brendel C Ex vivo hematopoietic stem cell (HSC) gene therapy is effective for non-malignant blood disorders including sickle cell disease (SCD), but requires hospitalization, ex vivo cell manipulation, and conditioning. Direct in vivo gene delivery could remove these barriers and widen access. Here, we explore phagocytosis-shielded lentiviral and alpha-retroviral vectors pseudotyped with the baboon endogenous retrovirus glycoprotein variant BaEVRLess for in vivo HSC gene transfer. Vector injection into mobilized humanized mice yielded up to 8.8% gene marking in hCD45+ cells, which chemoselection enriched to 70% of hCD45+ cells and 54% of HSCs. Barcode analysis showed polyclonal reconstitution in over 90% of mice, which remained stable in secondary recipients. For SCD, we targeted BCL11A and ZNF410 selectively in erythroid cells using miRNA-embedded shRNAs to derepress gamma-globin, reaching therapeutically relevant levels of 61.5% of beta-like globins. In summary, BaEVRLess-pseudotyped lentiviral vectors enable clinically relevant in vivo gene transfer and fetal globin induction for SCD. |
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JAMA Oncology Systemic Therapy Considerations in Older Adults with Early-Stage Breast Cancer: A Review Smith CE, Sammons SL, Minami CA, Hshieh TT, Smith S, Ruderman K, Bak K, Lin NU, Freedman RA IMPORTANCE: The treatment of older adults with chemotherapy for early-stage breast cancer involves a complex decision-making process that weighs the competing risks of disease recurrence against the potential harms of treatment. While older adults continue to be underrepresented in therapeutic clinical trials, there is a growing body of evidence to support optimal management of each subtype of early-stage breast cancer, including novel strategies like adjuvant cyclin-dependent kinase 4/6 inhibitors in hormone receptor-positive disease, and the neoadjuvant use of pembrolizumab in triple-negative breast cancer. OBSERVATIONS: The available evidence to support the systemic management of early-stage breast cancer in older adults with consideration of the data gaps for cytotoxic chemotherapy, de-escalated regimens, and targeted therapies is reviewed, and tools to optimize decision-making and supportive care for older adults with early breast cancer are presented. Clinicians should aim to avoid overtreatment when available evidence suggests a less intensive approach may suffice for a lower-risk cancer, and/or the patient is at high risk of serious toxic effects from chemotherapy treatment. On the other hand, undertreatment without consideration of the potential downsides may increase breast cancer-related mortality in older patients with higher-risk cancers. CONCLUSIONS AND RELEVANCE: This review will help clinicians best use the available data and decision-making tools to support best practice for treating older adults with early-stage breast cancer and will highlight ongoing clinical trials aimed at optimizing medical care for this patient population. |
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Journal of the National Cancer Institute Pregnancy History, Recency of Childbirth, and Outcomes in Young Women with Early-Stage Breast Cancer Nader-Marta G, Zheng Y, Rosenberg SM, Dibble KE, Mayer EL, Poorvu PD, Guzman-Arocho YD, Peppercorn J, Valenza C, Tayob N, Come SE, Polyak K, Partridge AH BACKGROUND: Breast cancer (BC) diagnosed during pregnancy or postpartum often presents with aggressive features, potentially influenced by hormonal, immunological, and tissue remodeling changes. Studies have suggested that postpartum BC may be associated with worse outcomes, though most evidence is retrospective and constrained by methodological limitations. This study evaluated associations between pregnancy history, recency of childbirth, and long-term outcomes in a prospective cohort of young patients with early-stage BC. PATIENTS AND METHODS: Patients aged ?40?years with stage I-III BC enrolled in the Young Women's Breast Cancer Study were categorized at diagnosis as nulligravid, nulliparous, pregnant, or parous (?5 vs 5 to 10?years postpartum). Analyses were stratified by BC subtype (estrogen receptor-positive [ER+]/HER2-, HER2+, and triple-negative [TNBC]), with distant recurrence-free survival (DRFS) as the primary endpoint. RESULTS: Among 859 patients, 257 (29.9%) were nulligravid, 50 (5.8%) nulliparous, 37 (4.3%) pregnant, and 515 (60.0%) parous. Pregnant patients had proportionally more TNBC, nodal involvement, T3/T4, and grade 3 tumors. After 11.1?years median follow-up, pregnancy or postpartum status was not independently associated with DRFS in multivariable models adjusted for age, tumor characteristics, and treatment, with consistent findings across ER+/HER2-, HER2+, and TNBC subtypes. Sensitivity analyses, including further categorization of postpartum diagnoses (<2 vs 2 to 5?years), yielded consistent results. CONCLUSIONS: Pregnancy history and recency of childbirth were not independently associated with long-term DRFS. Despite more aggressive features at diagnosis, patients diagnosed during or after pregnancy had comparable outcomes after adjustment, suggesting no adverse prognostic impact. CLINICAL TRIAL REGISTRATION: NCT01468246. |
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Journal of the National Cancer Institute 21-Gene Cecurrence Score Assay in pN2-3 Early-Stage Breast Cancer: A National Cancer Database Study Valenza C, Zheng Y, Leone JP, Nader-Marta G, Dominici LS, Tolaney SM, Partridge AH, Regan MM, Burstein HJ BACKGROUND: The clinical utility of the 21-gene recurrence score (RS) for guiding adjuvant chemotherapy in patients with pN2-3 early-stage breast cancer (eBC) has not been evaluated in prospective trials. This study aims to assess adjuvant chemotherapy benefit in patients with pN2-3 eBC who underwent RS testing and had a RS???25. METHODS: We conducted a retrospective cohort study from the National Cancer Database (NCDB) among patients with hormone receptor-positive/HER2-negative, pN2-3 eBC diagnosed from 2010-2020 who underwent 21-gene RS testing (OncotypeDX) and had RS???25. Overall survival (OS) was compared between patients who received or did not receive chemotherapy, using propensity score (PS)-weighted Cox regression. RESULTS: Among 50,229 eligible patients with pN2-3 eBC, 3,110 (6%) underwent RS testing. Patients who underwent testing had longer OS than those who did not (5-year OS: 86% vs. 79%). Among tested patients, 2,058 (66%) had RS???25 (median: 15), and 68% of them received chemotherapy. At a median follow-up of 5.3 years, the PS-weighted hazard ratio for OS comparing chemotherapy to no chemotherapy was 0.62 (95% CI: 0.48-0.81; P?=?0.0002; E-value: 2.13, 95% CI lower bound: 1.58). CONCLUSION: In this cohort of highly selected patients with hormone receptor-positive/HER2-negative pN2-3 eBC who underwent 21-gene RS testing and had RS???25, patients who received chemotherapy had a longer OS compared to those who did not receive chemotherapy, despite having similar characteristics. These results should be interpreted with caution, as the presence of confounding by indication and residual confounding in this analysis underscores the need for randomized clinical trials in this population. |
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Molecular Cell 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. |
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Molecular Cell Ribosome Remodeling Drives Translation Adaptation During Viral Infection and Cellular Stress Tsai HY, Liu L, Fleming RH, Mintseris J, Ekanayake D, Guo JA, Gu X, Gygi SP, Lee ASY The ribosome is the highly conserved molecular machine that decodes mRNAs during protein synthesis. Here, we discover that, while traditionally thought to consist of a uniform set of proteins, ribosome composition is reprogrammed to adapt to intrinsic and external cellular perturbations. During infection of human cells by non-segmented negative-sense viruses, viral entry into cells recruits the large ribosomal subunit protein rpL40 to a non-canonical site on the small subunit of 80S ribosomes near the mRNA entry site. These specialized ribosomes preferentially bind viral mRNAs to drive enhanced viral protein synthesis that is critical for replication under host pressures. Unexpectedly, we find that viruses have co-opted this translation pathway from a previously unrecognized endogenous ribosome remodeling program in which metabolic stress alters ribosome structure to promote mRNA translation required for cell survival. Thus, ribosome remodeling is a conserved mechanism that enables dynamic protein synthesis across pathogen and cellular adaptation. |
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Nature Medicine AI-Assisted Scoping Review of Code Sharing in Clinical Prediction Model Research Sounack T, Celi LA, Lindvall C, Pollard T Clinical prediction models are increasingly deployed to support diagnostic and prognostic decisions, making reproducibility essential for assessing their reliability and generalizability. Analytical code supports independent assessment of these processes, yet its availability in the literature remains limited. This scoping review quantifies current practices in sharing analytical code to inform the development of TRIPOD-Code, a reporting guideline for code availability and reproducibility. Here a large-language-model-assisted pipeline was developed to screen articles citing TRIPOD or TRIPOD+AI, extract repository links and assess retrieved repositories against 14 predefined reproducibility-related features. Among 3,967 articles, 482 (12.2%) included code-sharing statements. Sharing prevalence varied widely by journal and country. Repository assessment showed substantial heterogeneity in reproducibility features. These findings underscore the need for clearer expectations beyond code availability, including documentation, dependency specification and executable structure. Strengthening these practices may improve the usability of clinical prediction model studies and support their deployment in real-world clinical settings. |
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Nature Medicine Personalized Neoantigen-Targeting Cancer Vaccines in Ovarian Cancer: A Phase 1 Trial Sellars MC, Frank JA, Shim B, Vanasse A, Liu R, Forman C, Tu CR, Tabata KK, Kowelewski A, Cheng SC, Song C, Xiong K, Jain P, Crnjac A, Sax HE, Chea V, Lu W, Janes JT 3rd, Rickles-Young M, Sud A, Sarolkar S, Hayes M, Olive O, Greenslade H, Cibulskis C, Hacohen N, Fritsch EF, Li S, Livak KJ, Tayob N, Stover EH, Krasner C, Porter R, Matulonis U, Getz G, Oliveira G, Ott PA, Simon JM, Adalsteinsson VA, Keskin DB, Konstantinopoulos PA, Wu CJ Personalized neoantigen-targeting cancer vaccines in the adjuvant setting are of increasing interest across malignancies. Here we report the results of a phase 1 clinical trial testing the feasibility and safety of personalized neoantigen-targeting cancer vaccines for high-grade epithelial ovarian cancer. 'NeoVax' consisted of pools of synthetic long peptides targeting patient-specific neoantigens admixed with the immunostimulant poly-ICLC, was combined with delayed administration of anti-PD-1 antibody, and was tested in ten patients (one newly diagnosed patient (Cohort A) and nine patients at first recurrence (Cohort B)) with platinum-sensitive ovarian cancer following standard-of-care platinum doublet chemotherapy. Nine of 12 evaluable Cohort B patients were vaccinated (75%, 90% CI 47-93%) and 1 of 9 Cohort A patients (11%, 90% CI 0.6-43%). No unexpected safety signals were encountered and no patients discontinued treatment due to toxicity. Across patients, >70% selected targets remained detectable by noninvasive cell-free DNA analysis despite a median of 6.5 months from the time of diagnostic biopsy to vaccine administration, during which, patients received standard-of-care chemotherapy. Biomarker analysis was suggestive of biologic activity of the vaccine in six of ten patients and this was associated with broader tumor and vaccine-specific immune responses in blood and tumor following vaccination. Resistant tumor clones reflected diverse mechanisms affecting antigen presentation, indicative of immune-selective pressure exerted by vaccination. Overall, the interplay between the repertoire of antigens presented by the tumor and the breadth of induced immunity seemed to dictate clinical efficacy following vaccination. ClinicalTrials.gov identifier: NCT04024878. |
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Nature Medicine Some Answers, More Questions for Multi-Cancer Early Detection Tests Marinac CR, Rebbeck TR, O'Donnell EK In current practice, only about 13% of cancers are detected by guideline-based screening programs. Although these programs reduce mortality rates for some cancers, most cases and deaths are attributed to cancer types without recommended screening strategies. Current cancer screening approaches are largely organ-specific, and uptake is variable. These challenges have led to interest in blood-based multicancer early detection (MCED) tests as a complementary approach to existing screening strategies. Three contemporaneous publications, two in this issue of Nature Medicine and one in the New England Journal of Medicine, report results from the PATHFINDER 2 and NHS-Galleri trials, both evaluating the Galleri test, together providing some of the most substantial evidence so far on the implementation and clinical utility of MCED testing. |
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Nature Medicine 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. |
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New England Journal of Medicine Giredestrant plus Everolimus in Advanced Breast Cancer Mayer EL, Tolaney SM BACKGROUND: Giredestrant and everolimus target the estrogen receptor (ER) pathway and the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway, respectively, which are implicated in endocrine-therapy resistance. METHODS: In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had disease progression or recurrence after receipt of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor plus endocrine therapy. Patients were assigned, in a 1:1 ratio, to receive giredestrant plus everolimus (each given orally) or standard endocrine therapy (i.e., exemestane, fulvestrant, or tamoxifen) plus everolimus. The primary end point was investigator-assessed progression-free survival, evaluated first among patients with ESR1-mutated tumors and then in the overall trial population. RESULTS: Overall, 373 patients underwent randomization, with 183 assigned to the giredestrant-everolimus group and 190 to the standard therapy-everolimus group. Among 207 patients with ESR1-mutated tumors, the median progression-free survival was 10.0 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio for disease progression or death, 0.38; 95% confidence interval [CI], 0.27 to 0.54; P<0.001). In the overall population, the median progression-free survival was 8.8 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio, 0.56; 95% CI, 0.44 to 0.71; P<0.001). Adverse events occurred in 98.9% of patients who received giredestrant-everolimus and in 96.8% of those who received standard therapy-everolimus. The most common adverse events were stomatitis (in 47.3% of giredestrant-everolimus recipients and 48.9% of standard therapy-everolimus recipients), diarrhea (in 26.9% and 22.6%, respectively), and anemia (in 23.6% and 21.0%). CONCLUSIONS: An all-oral giredestrant-everolimus regimen led to significantly longer progression-free survival than standard endocrine therapy-everolimus among patients with ER-positive, HER2-negative advanced breast cancer who had received a CDK4/6 inhibitor previously, mainly in patients with ESR1-mutated tumors. The incidence of adverse events was similar in the two groups. (Funded by Genentech; evERA Breast Cancer ClinicalTrials.gov number, NCT05306340.) |
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Science Phage Proteases Activate CBASS Antiphage Immunity Hobbs SJ, Kranzusch PJ Cyclic oligonucleotide-based antiphage signaling systems (CBASS) are bacterial immune pathways evolutionarily related to cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) in humans. In CBASS, cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes sense phage infection and synthesize nucleotide signals to initiate antiviral defense. Here, we reveal phage prohead protease activity as a widespread mechanism of CD-NTase activation. We reconstitute CBASS recognition of phage T4 in vitro and identify proteolytic cleavage of a CD-NTase activation loop as a trigger of immune signal synthesis. Phage prohead proteases directly activate CBASS in vivo, explaining how immunity is initiated late during infection. Structure-based phylogenetic analyses identify activation loops in clade A, D, and G CD-NTases and define residues controlling recognition of distinct phage families. Our results establish CBASS recognition of phage protease activity as a widespread antiviral defense mechanism. |
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Advances in Radiation Oncology Orio PF, Devlin PM |
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American Journal of Clinical Oncology Hou HX, Roberts HJ, Pathak PS, Mamon HJ, Mancias JD, Singh H, Qadan M, Castillo CF, Koenig JL, Hong TS, Blaszkowsky CR, Blaszkowsky LS, Parikh AR, Allen JN, Clark JW, Weekes CD, van Dams R, Wo JY |
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American Journal of Hematology Plasma Exchange and Daratumumab for Myeloma Cast Nephropathy Shincovich CI, Chewcharat A, Adomi M, McGee EE, Kim R, Pirovano M, Bosques L, Porterfield FH, Somasundaram EV, Wells SL, Rubman MB, Pérez RS, Peterkin AC, Lima CSNH, Murakami N, Terashita M, Kim EB, Mosaheb K, Nadeem O, Leaf DE, Chowdhury RB, Stowell SR, Yee AJ, Leung N, Gupta S |
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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 Park KU, Sather BK, Shah A, Minami CA, Butler L, Love JA, McLean K, Dunn A, Mittendorf EA, King TA |
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Archiv de Pharmazie Intrinsic Reactivity of Sulfonyl Imidazole and Triazole Electrophiles for Covalent Probe Design Pal P, Unsworth H, Jones LH |
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Blood Advances Paolino JD, Hebert K, Yang J, Duncan CN, Margossian SP, Lehmann LE, Kapadia M, Whangbo JS, Takahashi T, Keating AK, Calderon FA, Horan JT, Burns MA, Davies K, Degar B, Vrooman LM, Kesselheim J, Feraco AM, Pikman Y, Place AE, Pollard JA, Kean LS, Neuberg DS, Baumeister SHC |
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Blood Advances Frost BF, Flamand Y, Baxter EW, Shimony S, Garcia JS, Wadleigh M, Winer ES, Volpe VO, Stone RM, DeAngelo DJ, Hergott CB, Brunner AM, Hock H, Fathi AT, Narayan R, Luskin MR, Chen EC |
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Blood Advances Harris EM, Tavares E, Montcrieff C, Chen N, London WB, Grace RF |
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Breast Molecular and Immune Profiling of HER2-Low, HER2 Ultra-Low, and HER2-Null Male Breast Cancer Trapani D, Lin NU, Abravanel DL, Tolaney SM, Leone JP |
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Breast Grinda T, Heiling HM, Tayob N, Davis R, Cotter C, DeMeo MK, Moy B, Savoie J, Mayer EL, Tolaney SM, Lin NU, Freedman RA |
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Cancer Florez N, Sands J, Aldea M, Rotow J |
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Cancer Delays in Breast Cancer Presentation, Diagnosis, and Treatment in Young Women Zhang BX, Sella T, Zheng Y, Kirkner GJ, Come SE, Peppercorn JM, Partridge AH, Brantley KD |
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Chemical Communications Schindler S, Dubey A, Mallis RJ, Reinherz EL, Arthanari H |
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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 HA, Poorvu PD, Partridge AH, Abravanel DL, Poorvu N, LeStage B, Sicinski P, Tolaney SM, Wagle N, Tayob N, Shapiro GI |
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Critical Care Explorations Upham EJ, Gouda SR, Lindvall C, DeCourcey DD |
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Current Opinion in Oncology Kitadai R, Lynce F, Garrido-Castro AC |
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EClinicalMedicine Nandi R, Khondoker NN, Uddin MM, Natarajan P, DeAngelo DJ, Luskin MR, Lindsley RC, Uno H, Shimony S, Weeks LD |
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EClinicalMedicine Lee DJ, Bertamini L, El-Khoury H, Allam S, Fleming G, Alberge JB, Perry J, Davis MI, Lightbody E, Redd R, Colchie J, Karlson EW, Rebbeck TR, Getz G, Ghobrial IM, Marinac CR |
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Elife Punctuated Mutagenesis Promotes Multi-Step Evolutionary Adaptation in Human Cancers Graser CJ, Wu W, Christini C, Michor F |
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Gynecologic Oncology Reports Chen RY, Vasavda C, Imadojemu S, Liu SW, Campos SM |
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Gynecologic Oncology Reports Towery EA, Stover EH, Kolin DL, Porter RL |
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HemaSphere Guijosa A, Tsakmaklis N, Dhe-Paganon S, Garbicz F, Carrasco R, Hatcher J, Pizzarella D, Kofides A, Liu S, Sun H, Liu X, Guerrera ML, Branagan AR, von Keudell G, Sarosiek SR, Castillo JJ, Hunter ZR, Treon SP |
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Hepatology Clinical Guideline for the Diagnosis and Treatment of Fibrolamellar Carcinoma O'Neill AF, Church A, Fitzgerald M, Kim HB, Lee SS, Rosenberg AR |
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Immunity Cancers Modulate Processing and Presentation of p53 Neoantigens to Evade T Cell Detection Haratani K, Reinhold B, Duke-Cohan JS, Fahey CG, Mallis RJ, Gusev A, Kehl KL, Luo J, Hennessey CJ, Blasco RB, Thai TC, Gibbons GM, Kivlehan S, Lizotte P, Paweletz CP, Aguirre AJ, Ligon KL, Chiarle R, Barbie DA, Reinherz EL |
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JACC CardioOncology Cardiovascular Toxicity of CDK4/6 Inhibitors in Breast Cancer: JACC: CardioOncology Primer Li M, Drachman DE, Mayer EL |
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JAMA Network Open Kamihara J, Cronin AM, Uno H, Horiguchi M, Fisher L, Schienda J, Vanderwall R, Khalaj A, Goler E, Hamilton KV, Garber JE, Diller LR, Rana HQ, Mack JW |
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JCO Oncology Practice Dias SL, Tramontano AC, Cronin CM, Hassett MJ |
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JMIR Research Protocols Cox E, Matarese E, Wilson RL, Gonzalez Castro LN, Uno H, Cooney T, Lane J, Norris MK, Bona K, Aziz-Bose R, Dieli-Conwright CM |
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Journal of Adolescent and Young Adult Oncology Venkataraman V, Revette A, Nava-Coulter B, George S, Shulman DS, Greenzang KA |
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Journal of Clinical Investigation Walmsley CS, Rodriguez A, Konstantinopoulos PA, Shapiro GI, Tolaney SM, Garber JE, Lynce F |
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Journal of Clinical Investigation Parashar Y, Sztupinszki Z, Wang X, Bala P, Cavale S, Ukaegbu C, Syngal S, Maoz A, Biller L, Lim R, Yurgelun MB, Szallasi Z, Sethi NS |
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Journal of Clinical Investigation Next-Generation CDK Inhibitors in HR+/HER2- Breast Cancer Seriak D, Kim JY, Shapiro GI, Giordano A |
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Journal of Clinical Investigation Li Y, Laimon YN, Cho H, Vivero M, De Oliveira GR, Seager MD, Delcea A, Savla V, Durmaz YT, Qiu X, Kukreja S, Li R, El Zarif T, Lu W, Van Orden M, Bronson RT, Li S, Barbie DA, Freedman ML, Long HW, Signoretti S, Oser MG |
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Journal of Clinical Investigation Toward Targeted Therapeutics for Lobular Breast Cancer Fanucci KA, Jeselsohn R |
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Journal of General Internal Medicine The Medicare Hospice Benefit's Origins: Lessons on End-of-Life Caregiving Knight HP, Leiter RE |
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Journal of Hematopathology Concurrent Presentation of Distinct Extranodal and Splenic Marginal Zone Lymphomas Grevet JD, Sadigh S, Kim AI |
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Journal of Infection Díaz MA, Coll AF, Gonzalez-Bocco IH, Flamand Y, Vivas L, Atallah CJ, Stone RM, DeAngelo DJ, Koo S, Luskin MR |
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Journal of Nuclear Medicine Ravi P, Zhong C, Perez KJ, Xie W, Volpe V, Lee GM, Boardman J, Pittard EG, Stoltenberg H, Jacene H, Weeks LD, Sperling AS |
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Journal of Pain and Symptom Management Pilot Study of Timely Integration of Interventional Pain Management for Advanced Cancer Wilson JM, Van Wieren I, Topiwala PS, Ross EL, Gorra M, Wright AA, Hassett M, Yong RJ, Gao R, Ferrick M, Gorman D, Lally K, Jamison RN, Enzinger AC |
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Journal of Pediatrics Hamilton KV, Nava-Coulter B, Revette A, Helu L, Cinelli A, Miguel C, Parad RB, Diller LR |
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Journal of the American Academy of Dermatology Low-Dose Long-Term Capecitabine for Refractory Field Cancerization: A Retrospective Cohort Study Neff H, Mortelliti C, Solomon B, Karn E, Stump M, Ran NA, Silk AW, Ruiz ES |
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Journal of the American Society of Nephrology Gupta S, Sharon E, Blau JA, Leaf DE |
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Kidney International Reports Qin Q, Ostendorf L, Wells SL, Gao C, Tran M, Alikhan FM, Zhang X, Chewcharat A, Rider RS, Prell SA, Chowdhury RB, Weins A, Shah SI, Mistry K, Bowman T, Villani AC, LeBoeuf NR, Selamet U, Ravi KS, Sharon E, Leaf DE, Sise ME, Rao DA, Wei K, Gupta S |
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Nature Methods SNP Calling, Haplotype Phasing and Allele-Specific Analysis with Long RNA-Seq Reads Huang N, Li H |
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Nature Reviews Clinical Oncology Tarantino P, Valenza C, Segui E, Lin NU, Waks AG, Tolaney SM |
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Neuro-Oncology Selective Histone Deacetylase Inhibition as a Therapeutically Relevant Strategy in H3K27M-Glioma Groves A, Kirkland OO, Lo Cascio C, Wang X, Heaslip C, Graca Marques J, Song C, Poetschke R, Wang T, Liu Q, Trissal M, Labelle J, Veiga Cruzeiro GA, Jones KL, Cameron AB, Clark LM, Leeper B, Nguyen QD, Filbin MG, Qi J |
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Neuro-Oncology Practice Mullins A, Rhee JY, Yeo KK, Salloum R, Gonzalez Castro LN |
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Oncologist Grinshpun A, Waks AG, Fu J, Kurnia P, Guo H, Li T, Moore M, DiLullo M, Patel A, Atanasov S, Partridge AH, Mayer EL, Krop IE, Santagata S, Brown M, Winer EP, Jeselsohn R, Lin NU |
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Pain Management Nursing Symptom Networks in Postsurgical Cancer Pain Across Recovery Stages Zhao J, Schreiber KL, DeForge SM, Wilson J PhD, Chai P, Edwards R, Azizoddin DR |
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Pediatric Blood and Cancer Access to Anticancer Drug Trials for Adolescents with Cancer in the United States Grobman B, Shulman DS, Venkataraman V, DuBois SG |
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Pediatric Blood and Cancer Burns MA, Flamand Y, Keating J, Koch V, Cronholm SM, Hunt SK, Neuberg DS, Place AE, Sallan SE, Vrooman LM |
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Pediatric Blood and Cancer Fattahi S, Yeap BY, Sethi RV, Shih HA, Ioakeim-Ioannidou M, Gonzalez E, Grabowski EF, Wiltsie L, Kamihara J, Yock TI, Tarbell NJ, Marcus KJ, Mukai S, Liu KX |
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Prostate Cancer and Prostatic Diseases Loda M |
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Supportive Care in Cancer Cardiopulmonary Exercise Testing to Measure Cardiorespiratory Fitness in Childhood Cancer Survivors Wilson RL, Dieli-Conwright CM |
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