Inavolisib is a selective phosphoinositide 3-kinase alpha (PI3Kα) inhibitor representing the next generation of anticancer drugs for the treatment of PIK3CA-mutated HR+/HER2- breast cancer. The dysregulated PI3K/AKT/mTOR signalling axis is an established mechanism of breast cancer progression and resistance to therapy, emphasizing the need for selective inhibitors that have both improved tolerance and efficacy. Inavolisib exhibits enhanced potency and selectivity for PI3Kα, resulting in superior antitumor activity and lower off-target effects than older generations of PI3K inhibitors. The present review provides a comprehensive discussion on inavolisib, covering its structure, pharmacokinetic properties, mechanism of action, and in vivo preclinical efficacy. The antitumor effects of combination strategies are also being highlighted for their potential to overcome endocrine resistance and optimize patient outcomes. Furthermore, it discusses the emerging resistance mechanisms to PI3K inhibition, mitigation of adverse effects, and future directions for inavolisib in personalized oncology. As studies continue to demonstrate its clinical utility, inavolisib exhibits preferential activity against the mutated PI3Kα isoform, thereby enhancing therapeutic specificity for combination therapy.
Bhatia et al. (2026) studied this question.