Narrowing the focus: Therapeutic cell surface targets for refractory triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2 protein. In comparison to other types of breast cancer, TNBC characterizes for its aggressive behavior, more prone to early recurrence and a disease with poor response to molecular target therapy. Although TNBC is identified in only 25%-30% of American breast cancer cases annually, these tumors continue to be a therapeutic challenge for clinicians for several reasons: Tumor heterogeneity, limited and toxic systemic therapy options, and often resistance to current standard therapy, characterized by progressive disease on treatment, residual tumor after cytotoxic chemotherapy, and early recurrence after complete surgical excision. Cell-surface targeted therapies have been successful for breast cancer in general, however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC. Recently, several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development. The purpose of this work is to review the current clinical challenges posed by TNBC, the therapeutic approaches currently in use, and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.

Keywords: Breast cancer, Triple negative, Biomarker, Cell surface, Targeted therapy, Chemorefractory

Core tip: Triple-negative breast cancer continues to be a challenge in breast cancer therapeutics, as these heterogeneous tumors are refractory to many effective and well-tolerated standard treatments. Even more concerning is the subpopulation of these tumors that progress even on the most aggressive therapeutic regimens. The core of this work reviews the developing approaches for treatment-refractory triple-negative breast cancer and proposes cell-surface targeting as a novel modality for targeted treatment of resistant disease.