Substrate adaptors are flexible tethering modules that enhance substrate methylation by the arginine methyltransferase PRMT5.

Protein arginine methyltransferase (PRMT) 5 is an essential arginine methyltransferase responsible for the majority of cellular symmetric dimethyl-arginine (SDMA) marks. PRMT5 uses substrate adaptors such as pICln, RIOK1, and COPR5, to recruit and methylate a wide range of substrates. Although the substrate adaptors play important roles in substrate recognition, how they direct PRMT5 activity towards specific substrates remains incompletely understood.

Physician-dominated conversations: An analysis of illness understanding discussions among patients with advanced cancer.

Context: Effective communication between patients and oncologists is crucial, particularly around illness understanding. When this communication is asymmetric or imbalanced, it can hinder shared decision-making and lead to suboptimal clinical outcomes.

Objectives: We sought to describe physician-patient speech imbalances ("asymmetry") in illness understanding portions of discussions between oncologists and advanced cancer patients and explore potential trends related to patient characteristics.

Epistaxis Versus Nonepistaxis Bleeding in Anticoagulated Patients With Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial.

Background: Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized.

Methods And Results: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) randomized 21 105 patients with atrial fibrillation and CHADS2 risk score ≥2 to higher-dose edoxaban regimen (60 mg daily, dose-reduced to 30 mg), lower-dose edoxaban regimen (30 mg, dose reduced to 15 mg, daily), or warfarin. Bleeds were adjudicated using International Society on Thrombosis and Haemostasis criteria.

Exploring oncology treatment strategies with tyrosine kinase inhibitors through advanced 3D models (Review).

The limitations of two-dimensional (2D) models in cancer research have hindered progress in fully understanding the complexities of drug resistance and therapeutic failures. However, three-dimensional (3D) models provide a more accurate representation of environments, capturing critical cellular interactions and dynamics that are essential in evaluating the efficacy and toxicity of tyrosine kinase inhibitors (TKIs). These advanced models enable researchers to explore drug resistance mechanisms with greater precision, optimizing treatment strategies and improving the predictive accuracy of clinical outcomes.

Secondary Esophageal Cancer After Hematopoietic Stem Cell Transplant: An Institutional Case Series.

Background: Development of secondary esophageal cancer after hematopoietic stem cell transplantation has been described; however, there is little consensus on treatment and surveillance for these patients. The objective of this study was to describe our experience treating patients with secondary esophageal cancer.

Methods: A retrospective chart review of prospectively collected data was performed to identify patients who underwent hematopoietic stem cell transplantation from 1997 to 2012 and in whom esophageal cancer developed later.

IRE1α-XBP1 safeguards hematopoietic stem and progenitor cells by restricting pro-leukemogenic gene programs.

Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.

Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).

Identification of key gene signatures for predicting chemo-immunotherapy efficacy in extensive-stage small-cell lung cancer using machine learning.

Objectives: The lack of definitive biomarkers presents a significant challenge for chemo-immunotherapy in extensive-stage small-cell lung cancer (ES-SCLC). We aimed to identify key genes associated with chemo-immunotherapy efficacy in ES-SCLC through comprehensive gene expression analysis using machine learning (ML).

Methods: A prospective multicenter cohort of patients with ES-SCLC who received first-line chemo-immunotherapy was analyzed.

Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.

Purpose: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.

Methods: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024.

Shared Local Oncology Care After Allogeneic Hematopoietic Cell Transplantation: A Randomized Clinical Trial.

Importance: Although sharing care with local oncologists after allogeneic hematopoietic cell transplantation (HCT) has been proposed for patients living far from HCT centers, it is not known whether a shared strategy is safe or improves patient quality of life (QOL).

Objective: To determine the efficacy and safety of sharing follow-up care after HCT between the HCT specialty center and local oncologists.

Design, Setting, And Participants: This was a multicenter collaborative randomized clinical trial of patients undergoing HCT at Dana-Farber Cancer Institute (DFCI)-a high volume HCT center in Boston (Massachusetts)-and 8 local oncology practices.

Central Nervous System Metastases in Breast Cancer.

Breast cancer metastasizing to the central nervous system (CNS) encompasses two distinct entities: brain metastases involving the cerebral parenchyma and infiltration of the leptomeningeal space, i.e., leptomeningeal disease.

Antibody-Drug Conjugates in Breast Cancer: The Road Towards Biologically-Informed Selection and Sequencing.

Purpose Of Review: In this review, we discuss evidence supporting the use of antibody-drug conjugates (ADCs) in breast cancer treatment, describe novel ADCs and combination regimens under development, and examine our current understanding of resistance mechanisms and biomarkers to guide ADC selection and sequencing.

Recent Findings: Three ADCs have proven benefit in patients with metastatic breast cancer: trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG). There are over two hundred investigational ADCs on the horizon, as pre-clinical studies work to identify novel ADC targets and structures.

A field resource for the glioma cerebrospinal fluid proteome: impacts of resection and location on biomarker discovery.

Background: While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown.

Methods: Aptamer-based proteomics was performed on 147 CSF samples from 74 patients, 71 of whom had grade 2-4 astrocytomas or grade 2-3 oligodendrogliomas.

Genomic profiling reveals SMARCA4 mutations are associated with shorter overall and intracranial progression free survival in melanoma brain metastasis patients.

Purpose: Melanoma brain metastases (MBMs) are a common, lethal complication of metastatic melanoma. Despite improvements in treatments, subsets of MBM patients experience rapid decline, and few prognostic biomarkers have been identified. An improved understanding of the molecular features specifically associated with MBM overall survival (OS) and intracranial progression free survival (PFS) could facilitate the development of more effective clinical management strategies.

Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: Primary analysis of the ELM-1 study.

Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) progressing after chimeric antigen receptor T-cell therapy (CAR T) have dismal outcomes. The prespecified post-CAR T expansion cohort of the ELM-1 study investigated the efficacy and safety of odronextamab, a CD20×CD3 bispecific antibody, in patients with disease progression after CAR T. Sixty patients received IV odronextamab weekly for 4 cycles followed by maintenance until progression.

Advancing Drug Development in Myelodysplastic Syndromes.

Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the United States Food and Drug Administration (FDA), (e.g.

T cell malignancies after CAR T cell therapy in the DESCAR-T registry.

The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.

The TRIPOD-LLM reporting guideline for studies using large language models.

Large language models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present transparent reporting of a multivariable model for individual prognosis or diagnosis (TRIPOD)-LLM, an extension of the TRIPOD + artificial intelligence statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion.

Targeting macrophages in cancer immunotherapy: Frontiers and challenges.

Background: Cancer immunotherapy has emerged as a groundbreaking approach in cancer treatment, primarily realized through the manipulation of immune cells, notably T cell adoption and immune checkpoint blockade. Nevertheless, the manipulation of T cells encounters formidable hurdles. Macrophages, serving as the pivotal link between innate and adaptive immunity, play crucial roles in phagocytosis, cytokine secretion, and antigen presentation.

Crypt density and recruited enhancers underlie intestinal tumour initiation.

Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signalling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny.

Divide and conquer, mitochondrial edition: Subpopulations direct cellular energy and nutrient supply.

Mitochondria produce energy and building blocks essential for cell growth. How these competing processes are balanced and sustained during nutrient scarcity remains unclear. Ryu et al.

Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer.

Purpose: Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non-small cell lung cancer (NSCLC); however, randomized data for resectable lung cancer are limited. We report results from the exploratory concurrently randomized nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial.

Methods: Adults with stage IB-IIIA (American Joint Committee on Cancer seventh edition) resectable NSCLC received three cycles of nivolumab once every 2 weeks plus one cycle of ipilimumab or three cycles of chemotherapy (on day 1 or days 1 and 8 of each 3-week cycle) followed by surgery.