Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches

Abstract

Angiogenesis is a vital process for the growth and dissemination of solid cancers. Numerous molecular pathways are known to drive angiogenic switch in cancer cells promoting the growth of new blood vessels and increased incidence of distant metastasis. Several angiogenesis inhibitors are clinically available for the treatment of different types of advanced solid cancers. These inhibitors mostly belong to monoclonal antibodies or small-molecule tyrosine kinase inhibitors targeting the classical vascular endothelial growth factor (VEGF) and its receptors. Nevertheless, breast cancer is one example of solid tumors that had constantly failed to respond to angiogenesis inhibitors in terms of improved survival outcomes of patients. Accordingly, it is of paramount importance to assess the molecular mechanisms driving angiogenic signaling in breast cancer to explore suitable drug targets that can be further investigated in preclinical and clinical settings. This review summarizes the current evidence for the effect of clinically available anti-angiogenic drugs in breast cancer treatment. Further, major mechanisms associated with intrinsic or acquired resistance to anti-VEGF therapy are discussed. The review also describes evidence from preclinical and clinical studies on targeting novel non-VEGF angiogenic pathways in breast cancer and several approaches to the normalization of tumor vasculature by targeting pericytes, utilization of microRNAs and extracellular tumor-associate vesicles, using immunotherapeutic drugs, and nanotechnology.

Correlations between dynamic-enhanced magnetic resonance imaging quantitative parameters and postoperative recurrence or metastasis and clinicopathological features in breast cancer patients—a retrospective cohort study

“…Our study showed that a decrease in peak time was a risk factor for postoperative recurrence or metastasis in breast cancer, which indicated that patients with more angiogenesis in breast cancer tumors were more likely to suffer from recurrence or metastasis after surgery. Previous studies have also confirmed that angiogenesis is a risk factor for postoperative recurrence or metastasis in breast cancer patients (18)(19)(20). A further analysis showed that peak time was more lowly expressed in high Ki-67 patients and more highly expressed in high ER and PR patients.…”

A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance

“…Angiogenesis is a pivotal process for BC growth and metastasis (Ayoub et al, 2022). LSD1 is also involved in this process via modulating several pathways (Table 2) (Li et al, 2011;Lee et al, 2017).…”

Neutrophils in pancreatic cancer: Potential therapeutic targets

“…Angiogenesis is a critical link in tumor growth and metastasis, and is jointly regulated by tumor cells, stromal cells and their bioactive products, such as various growth factors and extracellular matrix ( 55 ). Activated neutrophils release multiple angiogenic factors, including vascular endothelial growth factors (VEGFs), CXCLs and matrix metalloproteinases (MMPs), and form NETs ( 56 ).…”