Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer. (July 2020)

• Record Type: Journal Article
• Authors: du Rusquec, Pauline; Blonz, Cyriac; Frenel, Jean Sebastien; Campone, Mario
• Is Part Of: Therapeutic advances in medical oncology. Volume 12(2020)
• Publication Date: 2020-07
• Subjects: endocrine resistance -- HR positive advanced breast cancer -- PIK3 mutations -- PI3K/Akt/mTOR inhibitor -- PI3K/Akt/mTOR pathway; Oncology -- Periodicals; Cancer -- Treatment -- Periodicals; 616.994005
• DOI: 10.1177/1758835920940939
• Languages: English
• ISSNs: 1758-8340

Abstract

Recently many therapeutic classes have emerged in advanced hormone receptor-positive breast cancer, which is the leading cause of cancer death in women. In absence of visceral crisis, treatment relies on endocrine therapy combined with cyclin dependent kinase 4 and 6 inhibitor. Many mechanisms lead to resistance to endocrine therapy, including the activation of intracellular signaling pathways critical for cell survival. Approximately 70% of breast tumors harbor an alteration in the phosphoinositide 3 kinase (PI3K)/Akt pathway, leading to its hyper activation. This pathway is involved in the regulation of growth, proliferation and cell survival as well as in angiogenesis and is consequently a major target in the oncogenesis. An aberrant PIK3CA mutation is a common phenomenon in breast cancer and found in approximately 40% of patients with advanced hormone receptor-positive breast cancer. For the moment, the only positive trials showing a progression free survival benefit in this population are BOLERO-2 (2012), SOLAR-1 (2019), which tested everolimus, a mammalian target of rapamycin inhibitor, and alpelisib, a PI3K inhibitor, and led to their marketing authorization. However, many other inhibitors of this pathway are promising; nevertheless their development is actually limited by toxicity, mainly cutaneous (rash), digestive (diarrhea) and endocrine (diabetes).