Annexin A5 as a targeting agent for cancer treatment

Identifying a universal biomarker for cancer treatment remains a major challenge in cancer therapy. Extracellular exposure of phosphatidylserine (PS) is tightly regulated and is an “eat me” signal for phagocytosis in healthy cells. Although cancer cells and vasculature express high levels of externalized PS, they do not undergo apoptosis, making them a promising biomarker for cancer treatment. Annexin A5 (ANXA5) is the native binding partner of PS and can actively target and deliver chemotherapies to the tumor microenvironment (TME) via PS expression. ANXA5 acts as a bridge between the innate and adaptive immune systems and contributes to an immunostimulatory profile in the TME. ANXA5-enzyme prodrug therapies allow for systemic delivery of prodrugs and targeted killing at the tumor site. ANXA5–carbon nanotube conjugates have been used to physically ablate tumors via photothermal therapy. This review aims to explore the expression of PS in cancer cells and how ANXA5 has been used as a chemotherapeutic and targeting agent for cancer. •Annexin A5 (ANXA5) targets phosphatidylserine (PS) expression on cancer cells.•PS is upregulated and externally expressed on cancer cells' plasma membranes.•ANXA5 acts as a bridge between the adaptive and innate immune system.•ANXA5-enzyme fusion proteins convert prodrugs to cytotoxic agents at the tumor.•ANXA5-carbon nanotube conjugates ablate the tumor with photothermal therapy.