Endocrine resistance: mechanisms and therapeutic targets

Author(s): Senthil Damodaran, Sarmila Majumder, Bhuvaneswari Ramaswamy

Endocrine therapy remains the cornerstone in the effective management of estrogen receptor-positive breast cancers. Since the introduction of tamoxifen, the first therapy to target estrogen receptor, several agents have been approved to block the estrogen-mediated signaling in breast cancer management. However, successful clinical outcomes are hindered by the alternate survival mechanisms either innately active or developed by the cancer cell over time. Identifying these signaling pathways at the outset or over the treatment period, and developing targeted therapies to inhibit these pathways, would be crucial to improve clinical outcomes. This article reviews the landscape of the resistant pathways identified so far and the translational work that aims to target these pathways to enhance the effectiveness of endocrine therapy.