Dual therapeutic strategy targeting tumor cells and tumor microenvironment in triple-negative breast cancer

Objective: Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen receptors (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). Only 30% of TNBC patients show a pathologic complete response, and the other 70% of patients exhibit a less pronounced response followed by relapse and metastasis to distant organs after neoadjuvant chemotherapy. Achievements of immunotherapy targeting programmed cell death 1 ligand 1 (PD-L1) in clinical trials for treating melanoma, nonsmall-cell lung cancer, renal cell carcinoma, and TNBC suggest that targeting the interaction of tumor cells with tumor microenvironment is highly beneficial for cancer treatment. Finding a novel dual-targeting therapy against tumor cells and the tumor microenvironment (TME) may provide options for improved responses in TNBC patients. Data Sources: We searched the potential targeted therapy candidates that regulate tumor cells as well as the TME of cancer diseases, including TNBC, based on our previous and recent other publications. Study Selection: We selected the potential targeted therapies supported by relevance clinical data, in vitro and in vivo studies. Results: In this review, we found the KDM5B, Cadherin 11, β-catenin, CDK2, signal peptide CUB-EGF domain-containing protein 2, and PDL1 regulate the tumor cells and TME of TNBC cells. In addition, we also highlighted the Antrocin, Ovatodiolide, and Pterostilbene as natural small compound possess anti-cancer through the disruption of tumor cell–TME interactions. Conclusion: The new therapy approach targeting tumor cells-TME interaction may improve the response and survival rate of TNBC patients. Later, natural small compounds could provide alternative therapy options for TNBC patients.