PTEN as A Candidate Molecular Target That Links MVA Pathway and Anti-HER2 Therapy Resistance

Abstract

Drug resistance remains a major problem hampering the success of targeted treatment in cancer therapy. Despite the promising future of targeted therapy, the occurrence of drug resistance leading to poor therapeutic response has been recorded in a large number of patients. The underlying mechanism however is not conclusive. Cholesterol has been associated with the development of breast cancer and its link to drug resistance in this type of cancer could be a new branch of study. Targeting cholesterol biosynthesis for cancer therapy via mevalonate (MVA) pathway is currently demonstrated as an attractive approach for overcoming treatment resistance in HER2+ breast cancer. Here, we discuss the overview of MVA pathway components in breast cancer treatment and resistance as well as the potential use of MVA pathway inhibitors in breast cancer therapy as a new approach to the problem. We also highlight the role of PTEN deficiency, a well-known resistance mechanism in HER2+ breast cancer cells, as a possible new target of the HMGCR inhibition that could be exploited to reverse anti-HER2 resistance.