Combined inhibition of WNT and NOTCH signaling as a therapeutic strategy for human clear cell kidney carcinoma

Current therapies for metastasized kidney cancer in humans include treatments with multi-tyrosine kinase inhibitors, monoclonal antibodies against VEGF or inhibitors of mTOR. While many tumors initially respond to these treatments, nearly all resume their progression within two years. Here we characterize CXCR4+MET+CD44+ cancer stem cells in clear cell renal cancer (ccRCC), whose presence represents a major subgroup of the disease that correlates with the aggressiveness of the tumors and poor patient outcomes. Transcriptional profiling revealed that WNT and NOTCH signaling are activated in ccRCC cancer stem cells. Total RNA was extracted from non-cultured primary clear cell renal cell cancer (ccRCC) cells of three individual patients that were isolated after nephrectomy, sorted CXCR4+MET+CD44+ cells or spheres cultured for 7 days in non-adherent, serum-free condition.