Dana-Farber Cancer Institute

Extended Follow-Up of Botensilimab Plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer Without Active Liver Metastases

PURPOSE: Microsatellite-stable metastatic colorectal cancer (MSS mCRC) has limited treatment options and responds poorly to conventional immunotherapy. We report extended follow-up results from a fully-enrolled, phase 1b cohort evaluating botensilimab (BOT; Fc-enhanced anti-CTLA-...

An enantioselective covalent inhibitor of BAX confers cytoprotection in vivo

No therapies directly block apoptosis in tissue injury or the many diseases driven by cell loss. The BCL-2 family protein BAX is a central mediator of this pathway and C126 resides within a key regulatory region where physiologic or pharmacologic ligands can activate or inhibit i...

Irritable Bowel Syndrome and Allergic Diseases: A Nationwide Study of 1.5 Million Adolescents

BACKGROUND: Recent evidence suggests an increased prevalence of irritable bowel syndrome (IBS) among individuals with allergic diseases, and several biological mechanisms have been proposed. This study aims to investigate the association between IBS and allergic diseases in a lar...

Impact of Response to Hypomethylating Agent‐Based Therapy on Survival Outcomes in the Context of Baseline Clinical‐Molecular Risk and Transplant Status in Patients With Higher‐Risk Myelodysplastic Syndromes/Neoplasms: An analysis From the International Consortium for MDS (icMDS)

Baseline IPSS-M risk, response to hypomethylating agent (HMA) therapy, and receipt of allogeneic stem cell transplant (allo-HCT) have all been individually shown to impact overall survival (OS) in patients with myelodysplastic syndromes (MDS). However, the prognostic impact of re...

OncoRAG: graph-based retrieval enabling clinical phenotyping from oncology notes using local mid-size language models

Abstract Oncology notes contain the richest clinical detail, yet they remain largely inaccessible at scale because extracting structured phenotypes requires either substantial language model infrastructure, curated training data, or cloud computing under regulatory constraints. W...

Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma

Renal cell carcinomas comprise multiple molecularly distinct cancers but most are treated empirically with therapies designed for clear cell RCC (ccRCC), the most common subtype, due to incomplete understanding of subtype-specific biology. We analyzed single-cell transcriptomes a...

Farnesyltransferase Enables Modular Assembly of Dual‐Functional Nanobody Conjugates for in Vivo Imaging of Inflammation

ABSTRACT Non‐invasive imaging of inflammation is critical for disease diagnosis, monitoring, and therapeutic evaluation. Nanobodies, due to their many unique properties, are emerging as powerful imaging agents; however, conventional non‐specific conjugation strategies often yield...

Elacestrant in Combination with Everolimus for Estrogen Receptor-Positive, HER2-Negative Previously Treated Advanced Breast Cancer: Results from ELEVATE

PURPOSE: Treatment options for progression on first-line endocrine therapy (ET)+CDK4/6i for ER-positive/HER2-negative (ER+/HER2-) advanced breast cancer (ABC) include ET plus targeted agents (CDK4/6i or PI3K/AKT/mTOR-pathway inhibitors). Elacestrant is the first single-agent oral...

Inhibition of KDM5A/B promotes antitumor innate immune responses in HHV-8/KSHV-positive B-cell lymphomas

Histone methylation is a dynamic and reversible epigenetic modification that critically controls the progression of human diseases, including infections and cancers. Here we reported that histone lysine demethylases (KDMs) in the KDM5 family KDM5A/B play profound roles in suppres...

The metabokine β-aminoisobutyric acid mediates exercise performance and skeletal muscle adaptation through a PGC1α-BAIBA-PPARδ axis

Abstract Exercise orchestrates an interorgan communication network, in which skeletal muscle releases signaling molecules known as myokines that contribute to exercise training-induced adaptations. We identified the muscle-derived metabolite beta-aminoisobutyric acid (BAIBA) as a...

Paediatric therapeutic development workshop on osteosarcoma

The fourth Paediatric Therapeutic Development Workshop focused on osteosarcoma, the most common primary bone cancer in children and young adults. Current treatment of osteosarcoma comprises surgery and chemotherapy. Outcome has shown very little improvement over the last four dec...

The hematology workforce in the United States: past, present, and strategies for the future

From 2017-2021, the American Society of Hematology (ASH) completed the largest study ever conducted of the hematology workforce in the United States (US). The study highlighted a deficit in the classical hematology (CH) workforce: despite very high CH clinical volumes encountered...

Splicing genes as main targets of differential splicing

Abstract Splicing of transcripts via the spliceosome machinery is a complex process involving a multitude of proteins and short noncoding RNAs. In addition to full-length transcripts with all exons in the genomically encoded order, alternatively spliced transcripts can also be pr...

The p97 adaptor p47/NSFL1C is necessary for stress granule dissolution after heat stress

Abstract Stress granules form in response to diverse cellular perturbations to sequester translation components until the stress is resolved. Stress granules are composed of RNA–protein assemblies in membrane-delimited structures and must be rapidly disassembled to release compon...

‘Talk CKD Options’: improving how clinicians communicate treatment options in advanced kidney disease using a conversation analysis-based training intervention

Abstract Background Most older people with kidney failure and multiple co-morbidities must decide between dialysis or conservative kidney management. Dialysis is often presented as the default, despite providing uncertain survival benefits in this population. The Optimising Staff...

Acquired resistance to the RAS(ON) multi-selective inhibitor daraxonrasib guides rational combination therapy strategies in pancreatic cancer

Abstract Daraxonrasib is an orally bioavailable RAS(ON) multi-selective tri-complex inhibitor of the oncogenic mutant and wild-type variants of N, H and KRAS. We previously reported encouraging efficacy in a phase 1/2 clinical trial evaluating daraxonrasib monotherapy at clinical...

Optimizing safety and efficacy of asparaginase and blinatumomab therapy in frontline acute lymphoblastic leukemia regimens in diverse health care settings—international expert consensus

Frontline blinatumomab combined with chemotherapy has resulted in improved outcomes in both pediatric and adult patients with acute lymphoblastic leukemia and is considered the new cornerstone of acute lymphoblastic leukemia treatment. The role of asparaginase in this new landsca...

Rural-Urban Disparities in Contemporary Systemic Therapy for Advanced Prostate Cancer

This cross-sectional study examines the associations of rural-urban residence and race with receipt of systemic therapy for advanced prostate cancer.

Cannabinoids suppress chemotherapy- and ionizing radiation-induced apoptosis of glioblastoma cells

Abstract Cancer patients are increasingly exposed to cannabinoids, the bioactive molecules produced by the Cannabis sativa La. plant. This trend is being driven by several factors: expanding cannabis legalization, FDA approval of select cannabinoids for the treatment of seizures...

Longitudinal evaluation of sleep disturbances in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

Abstract Purpose The current study examines longitudinal changes in sleep disturbances and the risks they pose for new-onset health conditions in survivors of childhood cancer. Methods Five-year survivors ( N = 1081; median [range] age 50.0 [45.2–55.0] years) and siblings ( N = 2...