KRAS G12C Inhibition in Solid Tumors: Biological Breakthroughs, Clinical Evidence, and Open Challenges

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• KRAS is a frequently mutated oncogene in cancer, linked to aggressive tumors and therapy resistance.
• The KRAS G12C mutation, common in colorectal and lung cancers, allows for targeted covalent inhibitor development.
• Sotorasib and adagrasib are approved therapies for KRAS G12C-mutant cancers, but challenges persist.

Purpose of the Study:

• To review recent advances in KRAS G12C tumor biology.
• To summarize progress in the pharmacological targeting of KRAS G12C.
• To provide insights for overcoming resistance and optimizing treatment.

Main Methods:

• Literature review of recent scientific publications.
• Analysis of KRAS G12C tumor biology and resistance mechanisms.
• Evaluation of current and emerging pharmacological strategies.

Main Results:

• KRAS G12C inhibitors demonstrate clinical activity in NSCLC and CRC.
• Primary and acquired resistance are significant challenges to targeted therapy.
• Dose optimization and toxicity management require further investigation.

Conclusions:

• Targeted therapies for KRAS G12C-mutant cancers have emerged.
• Overcoming resistance and managing toxicity are critical for improving patient outcomes.
• Future research should focus on novel strategies to enhance the efficacy of KRAS G12C inhibitors.