Overcoming Resistance to Anti-Breast Cancer Drugs Targeting Kinases

Abstract

Although there are no definitive cures, breast cancer may be treated through administration of drugs targeting specific protein kinases. Protein kinases are prominent factors in breast cancer, as they are essential for tumor cell proliferation and are highly traceable targets. These kinases are often targeted because of their ubiquity and capacity to become oncogenic. Patients can develop resistance to kinase inhibitors, increasing the risk of recurrence. As kinase inhibitors continue to be developed and used in clinic, there is an increased need to overcome resistance. The acquired resistance by kinases responsible for the proliferation of breast cancer cells has rendered many therapeutic strategies obsolete. A further understanding of the mechanisms allowing tumor cells to bypass targeted kinase inhibition can lead to improved treatments and the development of more effective drugs. This literature review provides a summary of the current state of research into therapeutics targeting protein kinases associated with breast cancer. Current protein kinase inhibitors for breast cancer will be discussed, as well as resistance mechanisms associated with these inhibitors. Mechanisms of resistance can be classified into five categories: 1) gene mutations; 2) alternative signalling and transcriptional changes; 3) alterations in transmembrane transportation; 4) off-target drug binding, and 5) cellular transitions. This review aims to summarize the current research in protein kinase inhibitor resistance mechanisms and development of novel therapeutics.