Isolation And Molecular Characterization Of Circulating Melanoma Cells

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Melanoma is a highly invasive malignancy frequently presenting with blood-borne metastases, in which recent breakthroughs in targeted and immunological therapies highlight the need for both early detection of invasion and monitoring of drug responses. We adapted a microfluidic device to capture circulating tumor cells (CTCs) in patients with melanoma and in a mouse model. In eight patients followed longitudinally, CTC numbers were correlated with response and progression on B-RAF/MEK, CDK4/6 and PDL1 inhibitors. Consistent with this trend, in a mouse model of tamoxifen-inducible B-RAF/PTEN-driven melanoma, CTCs declined within four days of treatment with a B-RAF inhibitor. In this model, CTCs are shed very early in tumorigenesis, and a four week course of B-RAF inhibition after resection of the primary tumor is sufficient to prevent the subsequent development of cutaneous metastases. Whereas primary and metastatic mouse melanomas are highly similar, RNA sequencing of CTCs identifies significant differences in expression, generating a signature that is correlated with invasiveness and motility in human melanoma. Citation Format: Xi Luo, Devarati Mitra, Ryan J. Sullivan, Ben S. Wittner, Anya M. Kimura, Shiwei Pan, Mai P. Hoang, Brian W. Brannigan, Donald P. Lawrence, Keith T. Flaherty, Lecia V. Sequist, Shannon L. Stott, David T. Ting, Sridhar Ramaswamy, Mehmet Toner, David E. Fisher, Shyamala Maheswaran, Daniel A. Haber. Isolation and molecular characterization of circulating melanoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4832. doi:10.1158/1538-7445.AM2014-4832