Abstract: The present invention provides methods for direct killing of cancer cells using anti-?5?1 antibodies. Generally, the method comprises contacting a cancer cell that expresses ?5?1 on its surface with an anti-?5?1 antibody, and thereby inducing the death of the cancer cell. The methods of the invention may be employed at an early stage of cancer development in a patient to prevent tumor establishment. In addition, the methods may be used to treat previously formed tumors especially in cancer that have not proven susceptible to anti-angiogenesis therapy. The methods may be employed as a combination therapy of anti-?5?1 antibodies together with cancer chemotherapeutic agents or other molecular-based cancer therapeutic agents.