Abstract 600: Melanoma and ovarian cancer cells tested for drug sensitivity using anchorage-independent growth

Abstract

Abstract This study aims to test patient-derived melanoma and ovarian cancer cells for their sensitivity to clinically available drugs and drug combinations. The experiments were performed by using the growth in low attachment (GILA) assay, which is equivalent to the classic soft-agar assay and allows screening of 3D ex vivo cultures, which resemble the tumor and its microenvironment. To assay tumor cells from malignant lesions we isolated ovarian cancer cells from peritoneal fluid (ascites) derived from patients and melanoma cells from metastatic melanoma patients. The fresh samples were enriched for tumor cells and later cultured in an ex vivo manner on either high- or low-attachment surfaces. These cells were subjected to drug treatments and cellular viability was measured at the end of these experiments. Our experiments demonstrate that the GILA assay is a highly sensitive method for pharmacological tests, as compared to the traditional 2D method (growth on high-attachment surfaces). By using GILA assay we found that melanoma cells are sensitive to drugs that inhibit driver oncogenes, such as BRAF or MEK. In addition, we found interesting targets in metastatic melanoma lesions that carry an unknown mutational background. Drug sensitivity assays for ovarian cancer cells using the GILA approach showed that cancer cells from various patients with the same cancer type display differential sensitivity to drugs. Additionally, ovarian cancer cells were found to have a different drug-sensitivity threshold when grown in spheres. Our studies present an approach that utilizes the unique ability of transformed cells to grow in anchorage-independent conditions and enables ex vivo drug sensitivity testing. This phenotypic approach is complementary to a genetic approach that uses DNA sequencing to identify putative oncogenes that confer sensitivity to drugs designed to specifically inhibit the identified oncoprotein. Citation Format: Asaf Rotem, Benjamin Izar, Levi A. Garraway. Melanoma and ovarian cancer cells tested for drug sensitivity using anchorage-independent growth. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 600.