The Role of VEGF, IL-8 and IGF in Sustaining Autophagic DIRAS3-induced Dormant Ovarian Cancer Xenografts

• Published in: Cancer 2019-01, Vol.125 (8), p.1267-1280
• Main Authors: Mao, Weiqun, Peters, Haley L., Sutton, Margie N., Orozco, Aaron F., Pang, Lan, Yang, Hailing, Lu, Zhen, Bast, Robert C.
• Format: Article
• Language: English
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.31935

Over the last 3 decades, despite improvement in 5-year survival for patients with ovarian cancer, the overall cure rate of approximately 35% has not changed due to late diagnosis and persistence of dormant, chemotherapy-resistant cancer cells. In more than 80% of cases, dormant ovarian cancer cells found at “second look” surgery express DIRAS3 and are undergoing autophagy. Selective elimination of dormant autophagic ovarian cancer cells could improve patient outcomes. In this study, we have found that neutralization of survival factors with monoclonal antibodies against VEGF, IL-8 and IGFR can drive dormant xenografts that express DIRAS3 to autophagic cancer cell death, curing the majority of mice. These studies could be translated to patients with minimal residual disease who might benefit from bevacizumab therapy, alone or in combination with monoclonal antibodies against IL-8 and/or IGFR. This could provide a novel approach to eliminating dormant, drug resistant ovarian cancer cells.