Tremelimumab and durvalumab as neoadjuvant or non-operative management strategy of patients with microsatellite instability-high resectable gastric or gastroesophageal junction adenocarcinoma: the INFINITY study by GONO.

Background: In resectable gastric/gastroesophageal junction adenocarcinoma (GAC/GEJAC), microsatellite instability (MSI-H) confers improved survival, but limited benefit from chemotherapy. Immunotherapy may eliminate the need of chemotherapy or surgery.

Patients And Methods: INFINITY is a multicentre, multicohort phase II trial (NCT04817826) investigating in Cohort 1 the activity and safety of tremelimumab+durvalumab (T300/D) as neoadjuvant treatment for dMMR/MSI-H, resectable GAC/GEJAC.

HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01.

DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomarker analysis aims to investigate relationships between biomarkers and clinical outcomes in patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH] positive) Cohort A (N = 53) of DESTINY-CRC01. Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd.

Prenatal THC exposure drives sex-specific alterations in spatial memory and hippocampal excitatory/inhibitory balance in adolescent rats.

The interaction between the main psychotropic ingredient of Cannabis, Δ⁹- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored sex-specific consequences of prenatal exposure to THC in hippocampus-dependent memory and the underlying cellular and molecular contributors of synaptic plasticity and E/I homeostasis.