Mechanism of Action of Adagrasib

Mechanism of Action of Adagrasib

Specific alterations in the KRAS gene produce an abnormally structured KRAS protein that remains persistently activated, continuously transmitting proliferative signals to cancer cells and leading to uncontrolled growth. Adagrasib is a highly selective small-molecule inhibitor that covalently binds to a specific cysteine residue on the mutant KRASG12C protein, locking it in an inactive state. By blocking the function of this protein, Adagrasib inhibits multiple downstream signaling pathways (such as the MAPK pathway), thereby slowing cancer cell growth and spread; additionally, the drug induces programmed cell death (apoptosis) in cancer cells, further enhancing its antitumor effect.

What is Adagrasib?

Adagrasib is a prescription medicine used to treat advanced non-small cell lung cancer, with the active ingredient adagrasib. The drug received conditional marketing authorization in the European Union on January 5, 2024, for patients with specific lung cancer whose disease has progressed after prior systemic therapy. Adagrasib is supplied as oral tablets and should be taken under a doctor's guidance on a long-term basis until disease progression or unacceptable side effects occur. Because this medicine targets cancer cells harboring specific genetic mutations, compliance testing is required before use to confirm the presence of the corresponding molecular marker in the patient's tumor tissue.

Which patients is Adagrasib suitable for?

Adagrasib is indicated for adult patients with advanced non-small cell lung cancer whose cancer cells carry the KRASG12C mutation. Additionally, patients must have received at least one prior systemic therapy (e.g., intravenous chemotherapy or oral targeted therapy) and have experienced disease progression after that treatment. This means Adagrasib is primarily used for second-line and later-line treatment, filling a therapeutic gap for patients with KRASG12C mutations after previous treatment failure. Since KRASG12C mutations are relatively common in non-small cell lung cancer and conventional chemotherapy or immunotherapy has limited efficacy in these patients, Adagrasib offers a new targeted treatment option for this population.