Toxicity profiles of immunochemotherapy for gastric or gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis.

Purpose: Neoadjuvant immunochemotherapy is emerging as a promising regimen for patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. However, it remains unclear whether immunochemotherapy will bring more adverse events (AEs) leading to a delay or even cancellation of surgeries. We aimed to provide a comprehensive analysis of the toxicity profiles for immune checkpoint inhibitors (ICIs) combined with chemotherapy among patients with G/GEJ adenocarcinoma.

Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial.

Purpose: Neoadjuvant immunochemotherapy (NAIC) markedly induces pathologic regression in locally advanced gastric adenocarcinoma. However, specific biomarkers are still lacking to effectively identify the beneficiary patients for NAIC.

Patients And Methods: A prospective, single-arm, phase II study was conducted to treat locally advanced gastric adenocarcinoma with NAIC (NCT05515796).

Reduced intestinal-to-diffuse conversion and immunosuppressive responses underlie superiority of neoadjuvant immunochemotherapy in gastric adenocarcinoma.

Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment-naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis.

A Ubiquitin-Dependent Switch on MEF2D Senses Pro-Metastatic Niche Signals to Facilitate Intrahepatic Metastasis of Liver Cancer.

Effective treatment for metastasis, a leading cause of cancer-associated death, is still lacking. To seed on a distal organ, disseminated cancer cells (DCCs) must adapt to the local tissue microenvironment. However, it remains elusive how DCCs respond the pro-metastatic niche signals.

Aberrant RNA mA modification in gastrointestinal malignancies: versatile regulators of cancer hallmarks and novel therapeutic opportunities.

Gastrointestinal (GI) cancer is one of the most common malignancies, and a leading cause of cancer-related death worldwide. However, molecular targeted therapies are still lacking, leading to poor treatment efficacies. As an important layer of epigenetic regulation, RNA N6-Methyladenosine (mA) modification is recently linked to various biological hallmarks of cancer by orchestrating RNA metabolism, including RNA splicing, export, translation, and decay, which is partially involved in a novel biological process termed phase separation.

Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance.

SHARPIN stabilizes β-catenin through a linear ubiquitination-independent manner to support gastric tumorigenesis.

Background: Aberrant activation of Wnt/β-catenin signaling by dysregulated post-translational protein modifications, especially ubiquitination is causally linked to cancer development and progression. Although Lys48-linked ubiquitination is known to regulate Wnt/β-catenin signaling, it remains largely obscure how other types of ubiquitination, such as linear ubiquitination governs its signaling activity.

Methods: The expression and regulatory mechanism of linear ubiquitin chain assembly complex (LUBAC) on Wnt/β-catenin signaling was examined by immunoprecipitation, western blot and immunohistochemical staining.

Norrin maintains malignancy of gastric cancer cells in part through activating AKT signaling.

Human tumorigenesis resembles embryogenesis by aberrant activation of several developmental pathways including Wnt/β-catenin signaling. Norrin is an atypical ligand for Frizzled receptor that is preferentially expressed in the endothelium to promote retinal vascularization during development. However, its expression pattern and potential roles in human cancers remain unclear.

Epigenetic restriction of Hippo signaling by MORC2 underlies stemness of hepatocellular carcinoma cells.

The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC).

miRNA-regulated delivery of lincRNA-p21 suppresses β-catenin signaling and tumorigenicity of colorectal cancer stem cells.

Cancer stem cells (CSCs) are key cellular targets for effective cancer therapy, due to their critical roles in cancer progression and chemo/radio-resistance. Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) are important players in the biology of cancers. However, it remains unknown whether lncRNAs could be exploited to target CSCs.