Towards KRAS-directed therapy : Dependency of metastatic colorectal cancer cells on mutant KRAS

From KRAS inhibition to tumor adaptation: mechanistic layers of resistance and therapeutic strategies.

This review synthesizes current knowledge on KRAS resistance mechanisms and highlights emerging therapeutic strategies, including rational combination approaches, enhanced RAS pathway suppression, targeted protein degradation, and KRAS-directed immunotherapies.

[Novel therapeutic strategies for liver metastases driven by the common microenvironment].

Comparison of gene mutations of liver metastases to the primary tumor in colorectal cancer: lessons from a small cohort

Introduction Upfront molecular diagnostics are used to characterize genetic features of colorectal cancer, guiding therapy. Since colorectal cancer is usually surgically resected, these samples are used for such characterizations. The extent to which liver metastases maintain the genetic profile of the primary tumor is...

KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment

This review focuses on how allele-specific biochemical properties, tissue context, and co-mutational backgrounds shape KRAS signaling output, tumor progression, therapeutic response, and resistance; and discusses current diagnostic approaches and therapeutic strategies.

KRAS mutations as architects of the tumor immune microenvironment: implications for combination therapies

The recent approval of covalent KRAS G12C inhibitors, sotorasib and adagrasib, has revealed that targeted KRAS blockade can remodel the TME toward an immunostimulatory state, providing a mechanistic rationale for combining KRAS-directed agents with immune checkpoint blockade, STING agonists, and neoantigen vaccines.

Oncogenic KRAS in Cancer Immunotherapy: From Oncogenic Signaling to Tumor-Immune Ecosystem Regulation

Current evidence supports a paradigm in which KRAS functions not only as an oncogenic driver but also as a regulator of tumor-immune interactions, shaping therapeutic responsiveness and providing opportunities for biomarker-guided and combination-based immunotherapy in KRAS-mutant cancers.