Atypical Small Cell Lung Cancer: A New Malignancy Characterized by Chromothripsis, Carcinoid Tumors, and Wild-type RB1 and TP53.

Small cell lung cancer (SCLC) and pulmonary carcinoid tumors are traditionally seen as unrelated, with SCLC linked to smoking and characterized by biallelic loss of RB1 and TP53 and rapid progression. Rekhtman and colleagues upend these assumptions by discovering an "atypical" SCLC that arises in nonsmokers with intact RB1 and TP53 loci, chromothripsis-induced oncogene amplifications on extrachromosomal DNA, and frequent synchronous carcinoid tumors. See related article by Rekhtman et al.

Factors Associated With Minority Patient Enrollment in a Gastric Cancer Biobank.

Introduction: Human tissue samples are essential for translational cancer research. However, less than 20% of current biobank and genomic samples were obtained from minority patients, which may lead to biased understanding of cancer biology. The objective of this study was to identify factors associated with patient enrollment in our institution's gastric cancer biobank.

Obesity reshapes regulatory T cells in the visceral adipose tissue by disrupting cellular cholesterol homeostasis.

Regulatory T cells (T) accumulate in the visceral adipose tissue (VAT) to maintain systemic metabolic homeostasis but decline during obesity. Here, we explored the metabolic pathways controlling the homeostasis, composition, and function of VAT T under normal and high-fat diet feeding conditions. We found that cholesterol metabolism was specifically up-regulated in ST2 VAT T subsets.

Registry versus claims-based index dates for studies of cancer diagnosis in administrative data.

Purpose: Studies of healthcare encounters leading to cancer diagnosis have increased over recent years. While some studies examine healthcare utilization before the cancer registry date of diagnosis, relevant pre-diagnosis interactions are not always immediately prior to this date due to date abstraction guidelines. We evaluated agreement of a registry date with a claims-based index and examined Emergency Department (ED) involvement in cancer diagnosis as an example of possible pre-diagnostic healthcare misclassification that could arise from improper date choice.

Tryptophan metabolite atlas uncovers organ, age, and sex-specific variations.

Although tryptophan (Trp) is the largest and most structurally complex amino acid, it is the least abundant in the proteome. Its distinct indole ring and high carbon content enable it to generate various biologically active metabolites such as serotonin, kynurenine (Kyn), and indole-3-pyruvate (I3P). Dysregulation of Trp metabolism has been implicated in diseases ranging from depression to cancer.

Novel and potent MICA/B antibody is therapeutically effective in mutant lung cancer models.

Background: Concurrent (STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could pose an alternative therapeutic strategy through activation of natural killer (NK) cells.

Methods: Expression of NK cell activating ligands in NSCLC cell line and patient data were analyzed. Cell surface expression of MICA/B in NSCLC cell lines was determined through flow cytometry while ligand shedding in both patient blood and cell lines was determined through ELISA.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator's Consortium Registry Analysis.

Introduction: Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC.

Methods: Patients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator's Consortium were included; demographic and clinical data including treatment patterns were described.

Providing medically tailored groceries and food resource coaching through the charitable food system to patients of a safety-net clinic in Dallas, Texas: a randomised controlled trial protocol.

Introduction: Linking patients living with chronic, diet-related diseases and food insecurity to charitable food assistance, medically tailored groceries (MTGs) and food resource coaching may empower patients to better manage their health in a way that is economically sustainable. This protocol paper describes the implementation of a study evaluating MTGs and food resource coaching in a food pantry setting.

Methods And Analysis: A randomised controlled trial whereby patients of a safety-net health centre will be screened for The Emergency Food Assistance Program (TEFAP) and study eligibility.

Implementing a Novel "Frontiers in Neoplasia" Curriculum to Engage Fourth-Year Medical Students in Evidence-Based, Multidisciplinary Oncology Care.

Few medical students are exposed to evidence-based, multidisciplinary oncology care, and few studies in oncology education reflect consolidated pre-clinical curricula. We developed a four-week curriculum, "Frontiers in Neoplasia," for fourth-year medical students, which included didactic lectures, interactive site visits, and team-based simulations of tumor boards and clinical trial design. A mixed methods approach was utilized to investigate the course's impact on students' understanding and interest in oncology, involving pre- and post-course responses to Likert-scale and open-ended questions.

Organization Theory for Implementation Science (OTIS): reflections and recommendations.

Organizations exert influence on the implementation of evidence-based practices and other innovations that are independent of the influence of organizations' individual constituents. Despite their influence, nuanced explanations of organizations' influence remain limited in implementation science. Organization theories are uniquely suited to offer insights and explain organizational influences on implementation.

Neighborhood Factors related to Cancer Screening in Texas: a spatioecological study.

Introduction: To examine the associations of neighborhood socioeconomic status (nSES), ethnic enclaves, residential Black segregation with screening for breast, cervical and colorectal (CRC) cancers across the state of Texas (TX).

Methods: Using an ecologic study design, spatial clustering of low breast, cervical and CRC screening rates were identified across TX census tracts using local Moran's I statistics. Binomial spatial probit regression was used to estimate the associations between nSES, Hispanic/Latino and Asian American (AA) ethnic enclave neighborhoods and residential Black segregation with geospatial clusters of low screening, adjusting for behavioral characteristics.

Caveolin-1 regulates context-dependent signaling and survival in Ewing Sarcoma.

Cellular plasticity is a hallmark function of cancer, but many of the underlying mechanisms are not well understood. In this study, we identify Caveolin-1, a scaffolding protein that organizes plasma membrane domains, as a context-dependent regulator of survival signaling in Ewing sarcoma (EwS). Single cell analyses reveal a distinct subpopulation of EwS cells, which highly express the surface marker CD99 as well as Caveolin-1.

Cancer mutations rewire the RNA methylation specificity of METTL3-METTL14.

Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most -methyladenosine (mA) modifications in messenger RNAs (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context for mA can promote oncogenesis.

Phase II Study of Defactinib (VS6063) in Patients With Tumors With Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U.

Purpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.

Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology.

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing.

NCCN Guidelines® Insights: Survivorship, Version 2.2024.

The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and immunizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel's current recommendations regarding sexual health and fertility.

Achieving theranostic probes targeting BRD3/BRD4 for imaging and therapy of tumor.

The BET family proteins play pleiotropic roles in the tumorigenesis and growth of various human malignancies that have aroused great interests as the cancer therapeutic targets. Therefore, it's significant to develop labeling toolkits for the dynamic monitoring of BET family proteins in living tumor cells and tissue slices. In particular, there are few small-molecule fluorescent probes based on BET family proteins developed for real-time imaging of these proteins in tumor cells and tissues and treatment of breast cancer.

DPAM-AI: a domain parser for AlphaFold models powered by artificial intelligence.

Motivation: Due to the breakthrough in protein structure prediction by AlphaFold, the scientific community has access to 200 million predicted protein structures with near-atomic accuracy from the AlphaFold protein structure DataBase (AFDB), covering nearly the entire protein universe. Segmenting these models into domains and classifying them into an evolutionary hierarchy hold tremendous potential for unraveling essential insights into protein function.

Results: We introduce DPAM-AI, a Domain Parser for AlphaFold Models based on Artificial Intelligence.

Variant reclassification and recontact research: A scoping review.

Purpose: A primary challenge in clinical genetics is accurate interpretation of identified variants and relaying the information to patients and providers. Inconsistencies around handling variant reclassifications and notifying patients, combined with the lack of prescriptive guidelines on re-evaluation, reanalysis, and return of variants, has created practice challenges. Although relevant empirical work has emerged, the scope and outcomes of this research have not been characterized.

Phase II Study of Sunitinib in Tumors With Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V.

Purpose: The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring - mutations.

Methods: EAY131-V, is an open-label, single-arm, phase II study.

Impact of racial, ethnic, and socioeconomic disparities on presentation and survival of HCC: A multicenter study.

Background: Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status.

Methods: We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival.

SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition.

Direct targeting of the -mutant protein using covalent inhibitors (G12Ci) acts on human non-small cell lung cancer (NSCLC). However, drug resistance is an emerging concern in this approach. Here, we show that MRTX849, a covalent inhibitor targeting the mutation, leads to the reactivation of the mitogen-activated protein kinase signaling pathway in MRTX849-resistant NSCLC and pancreatic ductal adenocarcinoma.