Druggable Molecular Targets for the Treatment of Triple Negative Breast Cancer

Abstract

Breast cancer (BC) is still the most common cancer among women worldwide. Amongst the subtypes of BC, triple negative breast cancer (TNBC) is characterized by deficient expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. These patients are therefore not given the option of targeted therapy and have worse prognosis as a result. Consequently, much research has been devoted to identifying specific molecular targets that can be utilized for targeted cancer therapy, thereby limiting the progression and metastasis of this invasive tumor, and improving patient outcomes. In this review, we have focused on the molecular targets in TNBC, categorizing these into targets within the immune system such as immune checkpoint modulators, intra-nuclear targets, intracellular targets, and cell surface targets. The aim of this review is to introduce and summarize the known targets and drugs under investigation in phase II or III clinical trials, while introducing additional possible targets for future drug development. This review brings a tangible benefit to cancer researchers who seek a comprehensive comparison of TNBC treatment options.

Keywords: Clinical trial; Drug therapy; Triple negative breast neoplasms.

Figure 1. Major druggable targets expressed as proteins or glycoproteins and functioning as receptors, ligands, channels, mitotic protein kinases or nuclear receptors.

TIM-3 = T cell immunoglobulin and mucin-domain containing-3; PD-1 = programmed cell death protein 1; PD-L1 = programmed death-ligand 1; Hh = hedgehog; VEGFR2 = vascular endothelial growth factor receptor 2; FGFR = fibroblast growth factor receptor; EGFR = epidermal growth factor receptor; GPNMB = glycoprotein non-metastatic B; Trop-2 = trophoblast antigen 2; AR = androgen receptor; CSF1R = colony stimulating factor 1 receptor; FZD = frizzled.

Figure 2. Major druggable signaling pathways with significant roles in triple negative breast cancer.

JAK = Janus kinase; IL = interleukin; RTK = receptor tyrosine kinase; PI3K = phosphoinositide 3-kinase; GPCR = G protein-coupled receptor; mTOR = mammalian target of rapamycin.