Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment.

In recent years, clinical trials investigating new drugs and therapeutic combinations have led to promising advances in breast cancer therapy. Subtyping breast cancers into hormone receptor (HR) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently the basis of diagnosing and treating this disease. In addition to endocrine and HER2-targeted therapies in their respective subtypes, evidence from recent preclinical studies have shown several targetable pathways that overcome resistance in the clinical setting.

The Role of Androgen Receptor in Breast Cancer.

The androgen receptor (AR) is a proven clinical target in prostate cancer. Recent research indicates that it is an emerging hormonal target in breast cancer as well, with potential clinical benefit in both estrogen receptor(ER) positive and negative tumors. Compared to the ER, AR contains unique functional domains with relevance to its altered role in human breast cancer.

Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.

Introduction: Progesterone receptors (PR) are emerging as important breast cancer drivers. Phosphorylation events common to breast cancer cells impact PR transcriptional activity, in part by direct phosphorylation. PR-B but not PR-A isoforms are phosphorylated on Ser294 by mitogen activated protein kinase (MAPK) and cyclin dependent kinase 2 (CDK2).

Estrogen and progesterone receptor isoforms: clinical significance in breast cancer.

The identification and exploitation of biomarkers that may predict response to anti-cancer treatments has the capacity to revolutionize the way that patients with cancer are treated. In breast cancer, the estrogen receptor (ER) and the progesterone receptor (PgR) are known to have a significant predictive value in determining sensitivity to endocrine therapies. Tumor expression of ER or PgR is known to affect clinical outcome and this information is often used to determine a patient's optimal treatment regimen.