Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) comprises a group of aggressive and heterogeneous breast carcinoma. Chemotherapy is the mainstay for the treatment of triple-negative tumors. Nevertheless, the success of chemotherapeutic treatments is limited by their toxicity and development of acquired resistance leading to therapeutic failure and tumor relapse. Hence, there is an urgent need to explore novel targeted therapies for TNBC. Receptor tyrosine kinases (RTKs) are a family of transmembrane receptors that are key regulators of intracellular signaling pathways controlling cell proliferation, differentiation, survival, and motility. Aberrant activity and/or expression of several types of RTKs have been strongly connected to tumorigenesis. RTKs are frequently overexpressed and/or deregulated in triple-negative breast tumors and are further associated with tumor progression and reduced survival in patients. Therefore, targeting RTKs could be an appealing therapeutic strategy for the treatment of TNBC. This review summarizes the current evidence regarding the antitumor activity of RTK inhibitors in preclinical models of TNBC. The review also provides insights into the clinical trials evaluating the use of RTK inhibitors for the treatment of patients with TNBC.

Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies

“…Ongoing research aims to further elucidate the efficacy of these inhibitors and explore combination therapies to improve patient outcomes. Tyrosine kinase inhibitors (TKIs) target aberrant signaling pathways in TNBC, including the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) pathways ( 74 ). Clinical trials investigating EGFR inhibitors, such as cetuximab and erlotinib, in combination with chemotherapy have shown mixed results in TNBC patients, highlighting the need for further research to identify predictive biomarkers and optimal treatment strategies.…”