PI3K/AKT/mTOR Inhibitor Drug Candidates for the Treatment of Hormone Resistant Breast Cancer: A Systematic Review

Abstract

Breast cancer is the second most diagnosed type of cancer in women, with approximately 2.3 million cases reported in 2020. According to estimates by Brazil's National Cancer Institute, there will be approximately 74,000 new cases in the three-year period 2023-2025. It is divided into 4 molecular subtypes, Luminal A, Luminal B (hormone-positive), HER-2 and triple-negative. Regarding treatment, particularly for the luminal subtypes, hormone therapy is fundamental, since they grow from estrogen stimulation. However, processes can occur that lead to therapeutic resistance, such as mutations in the PI3K/AKT/mTOR pathway, which acts in the regulation of various cellular functions. The search for drugs that inhibit this pathway as an alternative treatment may play a key role in overcoming this resistance. This systematic review aimed to study new candidate drugs for inhibiting the PI3K/AKT/mTOR pathway as an alternative treatment in cases of resistance to hormone therapy. The study was conducted in accordance with the PRISMA guidelines, using the PubMed database with the following terms: "breast cancer", "PI3K/AKT/mTOR", "immunotherapy" without restriction of year and language. A total of 36 articles were found and 3 were included in this review. The drug candidates presented promising results in terms of inhibiting the PI3K/AKT/mTOR pathway, as well as some advantages such as a reduction in adverse effects, an increase in the average density of cytotoxic T cells and greater expression of interferon signaling genes, which through their immunoregulatory function lead to an increase in the body's ability to react to tumor cells. Despite this, there is still a need for more studies on the subject, especially in vivo studies that can assess the biosafety and efficacy profile, with the aim of compiling sufficient data to make the introduction of these new drugs in breast cancer therapy a reality.