Mechanistic Foundations of KRAS-Driven Tumor Ecosystems: Integrating Crosstalk among Immune, Metabolic, Microbial, and Stromal Microenvironment

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated member of the RAS family of small GTPases (RAS). It affects about one-fifth of cancer cases. The tumor microenvironment (TME) is a multifaceted network of immune cells, metabolites, microbiota, stromal components, and extracellular matrix. It creates a dynamic ecosystem that supports malignant initiation, progression, and therapy resistance through bidirectional crosstalk with tumor cells. Emerging evidence reveals distinct TME landscapes shaped by wild-type versus oncogenic KRAS variants. Additionally, TME rewiring occurs during KRAS-targeted therapies. Deciphering these KRAS-dependent TME architectures and their therapeutic vulnerabilities represents a critical frontier for precision oncology. This review synthesizes key milestones and persistent challenges in KRAS inhibitor development. And it systematically evaluates how KRAS mutations orchestrated immunosuppressive niches, metabolic symbiosis, stromal remodeling, and microbiome dysbiosis, supported by mechanistic insights from preclinical and clinical studies. It further explores therapeutic opportunities arising from targeting TME interactions, including rational combinations of KRAS inhibitors with immune checkpoint blockade, metabolic agents, or microbiota-modulating strategies.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.