CTNNA1 (Catenin Alpha 1)

P=N/A, N=100, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

In this review, we discuss the range of predisposing germline HDGC variants and their effects, the mechanism of DGC initiation and growth, and current best practices for the diagnosis and management of this disease. Finally, we highlight emerging areas of research on the characterization, classification, and management of HDGC.

Further, we postulate that the history of Lynch syndrome may be useful to advance HDGC aetiology, namely strategies for identification of new candidate genes, rules for variant interpretation, sources of phenotypic heterogeneity, and improved surveillance protocols. This collected data will impact clinical perspectives, as well as future research programs addressing HDGC unmet challenges.

PROCA11 binds to the cell-cycle regulator CCAR2/DBC1 and to CTNNA1, controlling cell adhesion and cytoskeleton. We suggest that PROCA11 arises early during tumor plasticity and controls the development of castration-resistant and neuroendocrine phenotypes in prostate cancer.

The choice of reconstruction (Roux-en-Y, jejunal interposition, double-tract) affects both duodenal accessibility and quality of life. Decisions between surveillance and surgery should be made individually, balancing cancer risk and postoperative quality of life.

CTNNA1 loss promotes cell invasion and migration, and BCL2L13 loss promotes anchorage-independent survival and non-cell-autonomous changes to macrophage polarization. This study demonstrates proof of principle that large-scale genetic screening can be performed in tumor-organoid models in vivo and identifies novel regulators of metastasis.

Considering the known psychological impact of a genetic cancer predisposition diagnosis and the significant postoperative lifestyle adjustment, this review identifies a need for standardized integration of mental health care along the PTG surgical continuum. The combination of the diagnosis of a hereditary cancer syndrome and the life-altering nature of prophylactic total gastrectomy (PTG) presents a psychosocial vulnerability for CDH1 (P/LP) variant carriers.

We provide compelling evidence supporting that CTNNA1-truncating variants positively associate with DGC and LBC, and NMD as the pathophysiological mechanism leading to CTNNA1 downregulation. We demonstrate that compared with CDH1, CTNNA1 is a moderate penetrance HDGC gene. This new knowledge is essential to define surveillance and/or prophylactic measures for CTNNA1-carrier individuals and families.

Importantly, our findings demonstrate that ubiquitylation serves as a molecular switch that directs the regulatory roles of CTNNA1 to cell-to-ECM adhesions. This study advances our understanding of how ubiquitylation fine-tunes protein function in cell adhesion dynamics.

High-risk patients showed elevated tumor immune dysfunction and exclusion (TIDE) score and increased sensitivity to oxaliplatin, gemcitabine, and targeted therapies. This study establishes RBP-based prognostic signatures, elucidates their mechanistic roles in CRC progression, and identifies potential therapeutic targets, providing a framework for personalized CRC management. Further validation in multicenter cohorts is warranted to translate findings into clinical practice.

In this case report, we discuss the rationale for EGFR-MEK co-inhibition in a patient with EGFR-mutated NSCLC treated with osimertinib that developed a CTNNA 1-BRAF fusion at progression. In addition, we provide a brief overview of the current evidence of BRAF fusions as an acquired resistance mechanism to osimertinib and potential treatment strategies.

This study systematically identified a set of shared genes between T2DM and CRC, along with the bioactive components and 10 potential targets of GQD for the treatment of T2DM and CRC. These findings provided a theoretical foundation for the combined therapy of T2DM and CRC.