Genomic and molecular alterations associated with primary resistance to immune checkpoint inhibitors.

The clinical response to immune checkpoint inhibitors may vary by tumor type and many tumors present with either primary or acquired resistance to immunotherapy. Improved understanding of the molecular and immunologic mechanisms underlying immunotherapy resistance is essential for developing biomarkers and for guiding the optimum approach to selecting treatment regimens and sequencing. This is increasingly important for tumors with primary resistance as effective biomarkers in this setting can guide clinicians about appropriate treatment regimen selection in the first-line setting.

Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies.

Background: The study summarizes the potential use of immunotherapy for mutated papillary thyroid cancer (PTC) by analyzing the immune profile of City of Hope PTC patient samples and comparing them to the thyroid dataset available in the TCGA database.

Materials And Methods: PTC cases with available formalin-fixed paraffin-embedded archived tumor tissue were identified. RNA was extracted from the tumor tissue and analyzed by NanoString to evaluate their immune gene expression profile.

Barriers to and enablers of physical activity participation in lung cancer survivors.

Background: Although physical activity has been shown to have significant benefits for individuals living with cancer, engaging lung cancer survivors (LCS) in increasing routine physical activity participation has been particularly challenging.

Purpose: To describe enablers of, barriers to, and patterns of physical activity among LCS and to characterize interest in a physical activity program as a first step to improving physical activity engagement.

Methods: The study consisted of a cross-sectional survey (n = 100) of adult LCS recruited from a thoracic oncology clinic assessing multiple domains of physical activity (engagement, perceived barriers, benefits, physical function, psychosocial factors, self-efficacy, and programmatic preferences).

BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors.

AdAPT-001 is an oncolytic adenovirus (OAV) with a transforming growth factor beta (TGF-ß) trap, which neutralizes the immunosuppressive and profibrotic cytokine, TGF-ß. The aim or purpose of this phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 after single intratumoral injection (IT) (Part 1) and multidose IT injection (Part 2) in patients with superficially accessible, advanced refractory solid tumors. Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.

Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer.

Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin β4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in tolerant cells improved sotorasib sensitivity, while overexpressing ITGB4 enhanced tolerance to sotorasib by supporting AKT-mTOR bypass signaling.