Sotorasib: A Targeted Breakthrough in KRAS G12C- Mutated Non-Small Cell Lung Cancer

Abstract

Sotorasib is a first-in-class targeted anticancer drug used in the treatment of non-small cell lung cancer (NSCLC) that carries a specific mutation called KRAS G12C. KRAS is a gene that normally controls cell growth, but when it mutates, it keeps sending "grow" signals to the cell, causing uncontrolled cancer growth. For many years, KRAS was considered "undruggable" because its structure made it very difficult to target with medicines. Sotorasib changed this by selectively and permanently binding to the mutated KRAS G12C protein, locking it in its inactive form and blocking the abnormal growth signal.This review focuses on the mechanism of action, pharmacokinetics, clinical efficacy, and safety profile of Sotorasib. It is administered orally, usually once daily, and has shown good absorption with hepatic metabolism. Clinical trials such as the CodeBreaK 100 study demonstrated meaningful tumor response rates and improved progression-free survival in patients with KRAS G12C-mutated NSCLC who had already received prior treatment. Common side effects include diarrhea, nausea, liver enzyme elevation, and fatigue, which are generally manageable with dose adjustments.Sotorasib represents an important advancement in precision oncology, offering a targeted treatment option for a specific genetic mutation rather than a one-size-fits-all chemotherapy approach. This review aims to help pharmacy students understand how molecular targeting works in modern cancer therapy and appreciate the significance of Sotorasib as a breakthrough drug in NSCLC management.