Tumor hypoxia provides a sanctuary to tumor initiating cancer cells and induce resistance to chemotherapy. Hypoxia also initiates peritoneal seeding and metastasis of ovarian cancer cells. Our studies have characterized a network of microRNAs regulating secretion of proangiogenic growth factors, metabolic reprogramming and increased cell motility. We have genetically deleted hypoxia-induced microRNA (knockout) in mice and currently investigating the loss of function of microRNA on angiogenesis, tumor growth, immunophenotype and metastasis. Tumor hypoxia is immunosuppressive ('cold tumors'). and prevents immune surveillance against cancer cells. We have genetically engineered a self-anchoring immunostimulatory molecule to prepare autologous cancer vaccines. Therapeutic efficacy of cancer vaccines are investigated in preclinical models either alone or in combination with anti-angiogenic and chemotherapeutic drugs.