Pharmacological Basis of Breast Cancer Resistance to Therapies - An Overview

Breast cancer (BC) is a molecular heterogeneous disease and often patients with similar clinico-pathological characteristics may display different response to treatment. Cellular processes, including uncontrolled cell-cycle, constitutive activation of signalling pathways parallel to or downstream of HER2 and alterations in DNA-repair mechanisms are the main features altered in the tumor. These cellular processes play significant roles in the emergence of therapy resistance. The introduction of target therapies as well as immunotherapies has improved the management of breast cancer. Furthermore, several therapeutic options are available to overcome resistance and physicians could overcome the challenge of resistant BC using combinatorial drug strategies and incorporating novel biomarkers. Molecular profiling promises to help in refine personalized treatment decisions and catalyse the development of further strategies when resistances inevitably occur. The search for biological explanations for treatment failure helps to clarify the phenomenon and allows to incorporate new biomarkers into clinical practice that can lead to adequate solutions to overcome it. This review provides a summary of genetic and molecular aspects of resistance mechanisms to available treatments for BC patients, and its clinical implications.