Potential therapeutic targets of triple-negative breast cancer based on its intrinsic subtype

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer, which is characterized as estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative. TNBC is the most difficult breast cancer subgroup to treat, due to its unresponsiveness to current clinical targeted therapies, high rate of recurrence, and poor prognosis. Thus, there is an urgent medical need to identify therapeutic targets and develop more effective stratified medicine for the treatment of TNBC. Here we review the potential therapeutic targets for TNBC based on its intrinsic subtype. We also review the aberrant activated signals found in different subgroups of TNBC, including androgen receptor (AR) and PI3K/AKT/mTOR, Notch, Wnt/β-catenin, Hedge-hog, and TGF-β signaling pathways, which play essential roles in multiple development stages of TNBC. The careful analysis of these signaling pathways and therapeutic targets would have significant impact on the drug development and clinical trials, leading to effective therapies for this deadly disease.

Comparative prognostic analysis for triple-negative breast cancer with metaplastic and invasive ductal carcinoma

“…TNBCs are histologically heterogeneous; the literature has repeatedly shown that TNBCs are heterogeneous in nature and understanding this characteristic has crucial clinical implications. Recent studies have identified six unique molecular subtypes, with important prognostic and predictive significance, which are potential targets for systemic therapy 27. Apart from the predominant invasive ductal carcinoma, TNBCs include metaplastic, medullary, apocrine, adenoid cystic, and invasive lobular carcinomas 6…”

LRP8 is overexpressed in estrogen‐negative breast cancers and a potential target for these tumors

“…There are currently no targeted treatments for TNBC, and this disease remains a major challenge for oncologists. Alternative treatments are therefore needed, to bypass chemoresistance and to improve the survival of TNBC patients …”

“…Alternative treatments are therefore needed, to bypass chemoresistance and to improve the survival of TNBC patients. 4,5,[8][9][10][11][12] Low-density lipoprotein (LDL) receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor-2 (APOER2), belongs to a superfamily of single-pass transmembrane receptors comprising LDL receptors (LDLR) and LDLR-related proteins (LRPs). 13,14 LRP8 displays high levels of sequence identity (50% in for the amino acid sequence) with the very-low-density lipoprotein receptor (VLDLR).…”

Prognostic significance of fatty acid binding protein‐4 in the invasive ductal carcinoma of the breast

“…Over the past decades, several monoclonal antibodies and small‐molecule inhibitors have been identified and their efficacy has been evaluated for whether they are useful in improving growth, survival, angiogenesis and metastasis. Thus, some of them have been reported to be effective in improving the survival and treatment outcomes in patients with BC …”

“…Thus, some of them have been reported to be effective in improving the survival and treatment outcomes in patients with BC. 7,8 To date, monoclonal antibodies (MABs) against epidermal growth factor receptor 2 (HER2) or vascular endothelial growth factor (VEGF), selective reversible inhibitors of HER1 and HER2, tyrosine kinases (e.g., Src), insulin-like growth factor (IGF)/IGF-receptor (IGFR), PI3K/AKT/mTOR inhibitors, RAS/ MEK/ERK inhibitors; Poly ADP ribose polymerase (PARP) inhibitors and MMP inhibitors have been developed as targeted treatment regimens for patients with BC. [9][10][11] As described here, targeted treatment regimens include agents that target growth, invasion, metastasis, angiogenesis and other key signaling pathways involved in tumorigenesis of the BC.…”