An update on promising and emerging protein kinase B/AKT inhibitors for breast cancer

Introduction: The PI3K pathway is crucial in breast cancer (BC), influencing cell survival, growth, and metabolism, with AKT playing a central role in treatment resistance. This pathway’s involvement in breast carcinogenesis and its link to treatment resistance underscores the significance of targeting it in BC therapy. PI3K-pathway inhibitors offer new therapeutic avenues but bring challenges, especially due to toxicity issues that hinder their development. Areas covered: This review discusses the PI3K-pathway inhibitors used in BC, highlighting emerging, innovative strategies. Expert opinion: The introduction of mTOR inhibitors marked a key step in tackling hormone receptor-positive (HR+) BC, targeting endocrine resistance. However, toxicity concerns remain, especially with PIK3CA and AKT inhibitors. Selective PI3K-targeted agents aim to reduce off-target toxicity, enhancing patient adherence and control over the disease. New compounds employing allosteric mechanisms may further limit adverse effects and allow safer combination therapies, previously limited by toxicity. Advancements in dosing strategies focus on patient-centered outcomes, and synergistic agents are essential in advancing AKT-pathway inhibition, paving the way for a new phase in HR+ BC treatment.