KRAS as a druggable target in NSCLC: Rising like a phoenix after decades of development failures

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Mitogen-activated protein kinase (MAPK) signaling is crucial for cancer development.
• KRAS mutations are frequent gain-of-function alterations in various cancers.
• KRAS mutations are the most common oncogenic drivers in non-small cell lung cancer (NSCLC), found in up to 25% of cases.

Purpose of the Study:

• To discuss the biology of KRAS in lung cancer.
• To explore the clinical implications of KRAS mutations in current and future oncology.
• To highlight the evolution of KRAS from a marker to a therapeutic target.

Main Methods:

• Review of scientific literature on KRAS mutations in lung cancer.
• Analysis of KRAS mutation profiles in different patient populations (smokers vs. never-smokers).
• Discussion of historical challenges and recent advancements in targeting KRAS.

Main Results:

• KRAS alterations are prevalent in NSCLC, with distinct profiles in smokers and never-smokers.
• Not all identified KRAS alterations function as driver mutations.
• Targeting KRAS, previously unsuccessful, now shows significant therapeutic promise.

Conclusions:

• KRAS mutations are critical oncogenic drivers in lung cancer.
• Understanding KRAS biology is essential for effective cancer therapy.
• KRAS represents a highly promising therapeutic target for NSCLC and other cancers.