Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

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.

Antigen experience history directs distinct functional states of CD8 CAR T cells during the antileukemia response.

Although chimeric antigen receptor (CAR) T cells are effective against B-lineage malignancies, post-CAR relapse is common, and efficacy in other tumors is limited. These challenges may be addressed through rational manipulations to control CAR T cell function. Here we examine the impact of cognate T cell antigen experience on subsequent CD8 CAR T cell activity.

Racial Disparities in Clinical Trial Enrollment Among Patients Diagnosed With Prostate Cancer: A Population-Based Cohort of Oncology Practices.

Although clinical trials should be accessible to all patients, persistent racial and ethnic disparities in clinical trial enrollment exist. Herein, we examine racial disparities in clinical trial enrollment among prostate cancer patients from a large population-based cohort of oncology practices in the United States. Using CancerLinQ Discovery, we identified men with regional (N1+) and/or metastatic (M1) prostate cancer diagnosed from 2011 to 2023.

MIRO2 promotes cancer invasion and metastasis via MYO9B suppression of RhoA activity.

Metastasis to vital organs remains the leading cause of cancer-related deaths, emphasizing an urgent need for actionable targets in advanced-stage cancer. The role of mitochondrial Rho GTPase 2 (MIRO2) in prostate cancer growth was recently reported; however, whether MIRO2 is important for additional steps in the metastatic cascade is unknown. Here, we show that knockdown of MIRO2 ubiquitously reduces tumor cell invasion in vitro and suppresses metastatic burden in prostate and breast cancer mouse models.

Patient-Reported Worst-Case Scenarios in Advanced Cancer: Presence, Contents, and Predictors.

Background: Advancements in precision oncology have led to a growing community of adults with advanced cancer who live longer but face prognostic uncertainty, with corresponding fears of the future. Their worst future fears related to cancer remain understudied, hindering support efforts.

Aims: This study aimed to characterize the presence, content, and predictors of imagined future worst-case scenarios related to cancer (WCS) among distressed adults with advanced cancer.

Impact of near continuous low dose rate neutron irradiation on pregnancy outcomes in mice.

The effects of galactic cosmic radiation on reproductive physiology remain largely unknown. We determined the impact of near-continuous low-dose-rate Californium-252 neutron irradiation (1 mGy/day) as a space-relevant analog on litter size and number of resorptions at embryonic day (E) 12.5 (n = 19 radiated dams, n = 20 controls) and litter size, number of resorptions, fetal growth, and placental signaling and transcriptome (RNA sequencing) at E18.

Single Cell RNA Sequencing Before and After Light Chain Escape Reveals Intra-patient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression.

High-risk multiple myeloma (MM) is genomically unstable, comprised of heterogeneous populations of tumor cells that evolve over time. Light chain escape (LCE) is a clinical phenomenon observed when light chains rise separately from M-spike values, implying divergent tumor evolution. We sought to understand LCE by performing high depth transcriptomic and phenotypic studies.

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.

CHD1L Inhibitor OTI-611 Synergizes with Chemotherapy to Enhance Antitumor Efficacy and Prolong Survival in Colorectal Cancer Mouse Models.

Colorectal cancer (CRC) is one of the most prevalent and deadly forms of cancer. It is universally treated with a combination of the DNA damaging chemotherapy drugs irinotecan, 5-Fluorouracil (5-FU), and oxaliplatin. is a novel oncogene that plays critical roles in chromatin remodeling and DNA damage repair, as well as the regulation of malignant gene expression.

Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Prevalence of the major thyroid cancer-associated syndromes in the United States.

Importance: A subset of thyroid cancers develops in a setting of a known hereditary cancer-associated syndrome. Understanding the population prevalence of thyroid cancer-associated syndromes is important to guide germline genetic testing and clinical management.

Objective: To estimate the prevalence of the major thyroid cancer-associated syndromes in the United States using the All of Us Research Program (AoU) data.

Returning actionable genetic results to participants in the biobank at the Colorado Center for Personalized Medicine and UCHealth.

Purpose: To describe our process for returning genetic results to participants in the Colorado Center for Personalized Medicine biobank.

Methods: Enrollment in the biobank is open to all adult UCHealth patients. Participants who provided a sample that was genotyped and signed the proper consent were eligible to receive results.

Transposable element activity captures human pluripotent cell states.

Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states.

Phase 1/2 trial of XPO1 inhibitor selinexor plus docetaxel in previously treated, advanced KRAS mutant non-small cell lung cancer.

Purpose: Patients with KRAS mutant non-small cell lung cancer (NSCLC) have limited therapeutic options. Based on activity of nuclear export inhibition in preclinical models, we evaluated this strategy in previously treated advanced KRAS mutant NSCLC.

Patients And Methods: The primary outcome of this multi-center phase 1/2 dose escalation trial of selinexor plus docetaxel was safety and tolerability.

Time to Next Systemic Therapy After Stereotactic Body Radiation Therapy for Oligoprogressive Metastatic Castrate-Resistant Prostate Cancer.

Purpose: Patients with metastatic castrate-resistant prostate cancer (CRPC) with progressive disease generally require a change or escalation in systemic therapy. For patients with limited (1-3) sites of progressive disease (oligoprogression), metastasis-directed therapy with stereotactic body radiation therapy (SBRT) may allow a longer interval before next-line systemic therapy.

Methods And Materials: This is a retrospective study of patients with oligoprogressive metastatic CRPC (mCRPC) treated with SBRT at a single center between 2011 and 2022.

The efficacy and safety of mirvetuximab soravtansine in FRα-positive, third-line and later, recurrent platinum-sensitive ovarian cancer: the single-arm phase II PICCOLO trial.

Background: Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with United States Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase II, global, open-label, single-arm trial of MIRV as third-line or greater (≥3L) treatment in patients with FRα-positive (≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC).

Patients And Methods: Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.

High-Risk Credit Borrowing Patterns: A Comparison of Cancer With Major Chronic Diseases.

Purpose: Although financial toxicity from cancer care is well documented, how cancer and other high-mortality chronic diseases affect credit overuse and high-risk borrowing remains unknown.

Methods: We retrospectively analyzed households in the 2012-2018 Health and Retirement Study. Outcomes included nonhousing financial debt and credit card debt.