Published Paper Details:

Capivasertib (AZD5363, Truqap) is a novel, orally active, selective pan-AKT inhibitor developed for the treatment of cancers driven by dysregulation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Aberrant activation of this pathway is frequently observed in various malignancies and is associated with uncontrolled cell proliferation, enhanced survival, metabolic reprogramming, and resistance to conventional anticancer therapies. Capivasertib exerts its anticancer effect by competitively inhibiting all three AKT isoforms (AKT1, AKT2, and AKT3), thereby suppressing downstream signaling involved in tumor growth and progression. Extensive preclinical studies demonstrated significant antitumor activity of capivasertib, particularly in cancer models harboring PI3K, AKT, or PTEN alterations. Subsequent clinical trials, including phase I, II, and III studies, established its safety, pharmacokinetic profile, and clinical efficacy. Notably, capivasertib in combination with fulvestrant has shown improved progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer, especially in biomarker-positive populations. Although the drug is associated with manageable adverse effects such as diarrhea, hyperglycemia, and rash, appropriate monitoring and dose modifications enhance its tolerability. This review provides a comprehensive and updated overview of the mechanism of action, pharmacological properties, preclinical and clinical evidence, safety profile, advantages, limitations, and future prospects of capivasertib as a targeted anticancer therapy.