Abstract
Activation of the phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is common in breast cancer. There is preclinical data to support inhibition of the pathway, and phase I to III trials involving inhibitors of the pathway have been or are being conducted in solid tumors and breast cancer. Everolimus, an mTOR inhibitor, is currently approved for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this review, we summarise the efficacy and toxicity findings from the randomised clinical trials, with simplified guidelines on the management of potential adverse effects. Education of healthcare professionals and patients is critical for safety and compliance. While there is some clinical evidence of activity of mTOR inhibition in HR-positive and HER2-positive breast cancers, the benefits may be more pronounced in selected subsets rather than in the overall population. Further development of predictive biomarkers will be useful in the selection of patients who will benefit from inhibition of the PI3K/Akt/mTOR (PAM) pathway.
Citations
Mar 23, 2017·Current Neurology and Neuroscience Reports·Nicole ShonkaManmeet S Ahluwalia
Mar 31, 2017·Cancer Chemotherapy and Pharmacology·Jing ChePeng Zhang
Jan 4, 2018·Oncotarget·Chengying XieLiguang Lou
Jul 10, 2018·Oncotarget·Aysegül KaymakHolger Richly
May 30, 2020·The Journal of Biological Chemistry·Mari GasparyanDuxin Sun
Sep 18, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·H WanL Wang
Nov 8, 2016·Frontiers in Pharmacology·Giuseppe TarantinoFabrizio Di Benedetto
Dec 20, 2018·Frontiers in Oncology·Fokhrul HossainLucio Miele
Jul 7, 2017·Oncology and Therapy·Adouda Adjiri
Jul 31, 2018·Oxidative Medicine and Cellular Longevity·Miguel A OrtegaNatalio García-Honduvilla
Feb 6, 2020·International Journal of Molecular Sciences·Alina Jaglanian, Evangelia Tsiani
Sep 20, 2020·ESMO Open·Byung Woog Kang, Ian Chau
Jun 24, 2018·Scientific Reports·Puja KhannaGyeong Hun Baeg
Apr 29, 2021·Scientific Reports·Daiju YokoyamaYoshiharu Sakai
Apr 20, 2021·Oncotarget·Duna H BarakehMalak Abedalthagafi
Jun 26, 2021·The Journal of Organic Chemistry·Bedadyuti Vedvyas PatiPonneri Chandrababu Ravikumar
Jul 25, 2021·Cancers·Alakananda Basu, Christoffer Briggs Lambring