Navigating the Complexity of PI3K/AKT Pathway in HER-2 Negative Breast Cancer: Biomarkers and Beyond.

The results of the SOLAR-1 and CAPItello-291, highlight the benefit of the ɑ-selective phosphoinositide 3-Kinase Pathway inhibitor (PI3Ki) alpelisib and the AKT inhibitor (AKTi) capivasertib in patients with hormone receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 (HER2)- negative metastatic breast cancer (mBC) that have PIK3CA/AKT1/PTEN tumour alterations. Although effective, these drugs are associated with significant toxicities, which often limit their use, particularly in frail patients. Following the recent incorporation of these agents into clinical practice, and with many others currently in development, significant challenges have emerged, particularly those regarding biomarkers for patient selection. This review will discuss biomarkers of response and their resistance to PI3K/AKT inhibitors (PI3K/AKTis) in HR+/HER- BC in early and advanced settings to ascertain which populations will most benefit from these drugs. Of the biomarkers that were analysed, such as PIK3CA, AKT, PTEN mutations, insulin levels,

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Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: GNM: meeting/travel grants from Roche, Bayer, and AstraZeneca (all outside the submitted work). EdA: Financial: Honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Lilly, Astra-Zeneca, MSD, Gilead Sciences; Travel grants from Roche/GNE and Astra-Zeneca; Research grant to my institution from Roche/GNE, Astra-Zeneca, and GSK/Novartis, Gilead Sciences; Non-financial: ESMO director of Membership 2023-2024 and BSMO President 2023-2026. UdG: Advisory Board: MSD, Bristol Myers Squibb, Janssen, Astellas, Sanofi, Bayer, Pfizer, Ipsen, Novartis, and PharmaMar. Institutional research grants: AstraZeneca, Sanofi, and Roche The other authors did not declare any conflict of interest.