Melatonin and Apatinib: Potential Therapeutic Agents in Cancer Treatment through Vascular Mimicry Formation: A Review

Cancer is one of the most challenging diseases, affecting millions of individuals worldwide. This disease is caused by the abnormal and uncontrolled growth of cells, which leads to damage to various tissues and organs of the body. The formation of vascular-like structures (vascular mimicry) is one of the most important reasons for cancer metastasis and drug resistance. These structures are formed by tumor cells without the involvement of endothelial cells. Melatonin, a natural hormone in the human body, can exert its antitumor effects through antioxidant, antiproliferative effects, induction of apoptosis, and inhibition of invasion and metastasis of cancer cells. The anticancer effects of apatinib have been approved as an antiangiogenic drug and VEGF receptor inhibitor. Apatinib is first used for advanced or metastatic cancers, such as gastric cancer, that have not responded to standard treatments. In addition, induction of apoptosis, inhibition of metastasis, and invasion have also been confirmed by treatment with apatinib in cancer. Considering the antitumor effects of melatonin and apatinib, it seems that the drug apatinib and the hormone melatonin are effective in inhibiting the formation of vascular mimicry and overcoming the therapeutic limitations caused by these structures. This review study examined the effects of melatonin and apatinib on the formation of vascular mimicry structures in various cancers. It is suggested that these two compounds enter the animal and then human study phases, and if the results are positive, they could be used as a treatment for patients with metastatic cancer.