Targeting the PI3K/AKT/mTOR Pathway in Hormone-Receptor Positive Breast Cancer: A New Frontier in Precision Therapy

Authors

Rina Mehra, Department of Medical Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
Arjun Nair, Department of Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
Sneha Iyer, Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
Karthik Raman, Centre for Integrative Biology and Systems Medicine, Indian Institute of Technology Madras (IIT-M), Chennai, India
Meera Joshi, Department of Oncology, Apollo Cancer Institute, Hyderabad, Telangana, IndiaFollow

Article Type

Article

Abstract

Background: Hormone receptor-positive (HR+) breast cancer represents the most common subtype among Indian women and is typically managed with endocrine therapies. However, resistance to such therapies-often driven by activation of the PI3K/AKT/mTOR signaling pathway-poses a significant clinical challenge and necessitates the development of targeted treatment strategies. Objective: This review aims to evaluate the molecular basis, therapeutic efficacy, safety profiles, and real-world applicability of PI3K/AKT/mTOR inhibitors in the management of HR+ breast cancer, with a focus on their relevance within the Indian healthcare landscape. Methods: A comprehensive narrative review was conducted by searching PubMed, Scopus, Web of Science, and Google Scholar for articles published between 2005 and 2025. Studies examining molecular mechanisms, clinical trials of PI3K/AKT/mTOR inhibitors, and their implementation in low- and middle-income countries, particularly India, were included. Data on progression-free survival, toxicity, cost, and biomarker relevance were extracted and synthesized thematically. Results: The review highlights the clinical utility of agents such as alpelisib and everolimus, which have demonstrated significant improvements in progression-free survival, particularly in patients with PIK3CA mutations. Alpelisib, in combination with fulvestrant, achieved a 5.3-month PFS benefit in mutation-positive HR+ patients, while everolimus combined with exemestane improved PFS by 4.6 months. However, access to these therapies in India remains limited due to high cost, restricted molecular diagnostic availability, and low incorporation into public oncology protocols. Conclusion: Targeting the PI3K/AKT/mTOR pathway presents a transformative opportunity in the treatment of HR+ breast cancer. While the clinical benefits of these targeted therapies are well-established, addressing implementation barriers in India-such as cost and diagnostic infrastructure-will be crucial to achieving equitable outcomes in precision oncology.

Keywords

PI3K, AKT, mTOR, Hormone receptor-positive breast cancer, PIK3CA mutation, Alpelisib

Recommended Citation

Mehra, Rina; Nair, Arjun; Iyer, Sneha; Raman, Karthik; and Joshi, Meera (2025) "Targeting the PI3K/AKT/mTOR Pathway in Hormone-Receptor Positive Breast Cancer: A New Frontier in Precision Therapy," Muthanna Medical Journal: Vol. 12: Iss. 1, Article 2.
Available at: https://muthmj.mu.edu.iq/journal/vol12/iss1/2

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This work is licensed under a Creative Commons Attribution 4.0 International License.