Biochim Biophys Acta Rev Cancer. 2026 Oct 24:189739. doi: 10.1016/j.bbcan.2026.189739. Online ahead of print.
ABSTRACT
Although endothelial dysfunction (ED) is a hallmark of cardiovascular diseases (CVDs), it is also being increasingly recognised as a key contributor to cancer pathophysiology and a determinant of the cardiovascular response to anticancer therapy. Dysfunctional endothelial cells in primary tumours and metastatic organs play a critical role in cancer cell intravasation and extravasation, whereas systemic ED in patients with cancer drives CVDs. Nevertheless, anticancer therapies, such as conventional chemotherapy, kinase inhibitors, immune checkpoint inhibitors, and antibody-drug conjugates, drive cancer therapy-related ED (CTR-ED) and thus contribute to cancer therapy-related cardiovascular toxicity (CTR-CVT). In contrast, major CVD therapies such as statins, renin-angiotensin system inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors improve endothelial function. It is now evident that the opposite effects of CVD and cancer therapies on endothelial function-improving or worsening it, respectively-have critical therapeutic implications. Therefore, this narrative review provides an integrated pathophysiological perspective on ED in cancer, highlighting endothelial cells as a key pathophysiological component of the tumour microenvironment, metastatic organ, and systemic circulation involved in the regulation of primary tumour angiogenesis, metastasis, and systemic inflammation, as well as contributing to CTR-CVT, thus highlighting ED as a determinant of therapeutic outcomes in oncology. Nevertheless, ED, and particularly CTR-ED, represents a neglected frontier in anticancer therapy, calling for a paradigm shift toward endothelium-safe and vasoprotective treatment strategies in cancer care.
PMID:42926004 | DOI:10.1016/j.bbcan.2026.189739