PD-1/PD-L1 inhibitors combined with anti-angiogenic drugs for advanced triple-negative breast cancer: Synergistic mechanisms and research progress

Abstract

Triple-negative breast cancer (TNBC), a subtype of breast cancer that is highly aggressive and lacks effective therapeutic targets, has a particularly grim prognosis, with advanced patients having a significantly shorter median survival and showing resistance to chemotherapy. The introduction of immunotherapy has brought new hope for cancer treatment, but the use of immune checkpoint inhibitors（ ICI） alone in TNBC is ineffective, and there is an urgent need to explore more effective combination therapies.The combination of PD-1/PD-L1 inhibitors and anti-angiogenic drugs（AADs） can produce synergistic effects and open up new therapeutic avenues for TNBC patients. Specifically, inhibition of the vascular endothelial growth factor（VEGF） signaling pathway induces normalization of tumor vasculature, which in turn promotes infiltration of CD8 + T lymphocytes(CD8 + T cells）. Meanwhile, PD-1/PD-L1 inhibitors can similarly promote normalization of tumor vasculature and enhance the function of effector T cells by activating effector T cells and upregulating γ-interferon (IFN-γ) secretion. This combination regimen has demonstrated encouraging efficacy in several clinical studies. In this article, we comprehensively analyze the latest advances in the field,and provides insights into the application, mechanism of action, signaling pathways, clinical translational prospects, and shortcomings of anti-PD-1/PD-L1 drugs combined with anti-angiogenic drugs in advanced TNBC. This study aims to provide clues for the individualized treatment of TNBC, with a view to realizing precision medicine, reducing the risk of recurrence and metastasis in patients, and improving the poor prognosis, which has an important clinical practice value.