Colorectal cancer (CRC) is one of the most prevalent forms of cancer with over 150,000 new cases reported each year. Stage 4 CRC patients have very poor survival rates at only 11% and there are currently no effective therapeutics for treating metastatic CRC. The epithelial-mesenchymal transition (EMT) is a driving force for tumor progression, tumor cell heterogeneity, multi-drug resistance (MDR), evasion of the immune response and immune therapy, and metastasis. Dr. Daniel LaBarbera, with a team at the University of Colorado, has identified that TCF-transcription functions as a master regulator of EMT, and has discovered a novel factor within the TCF-transcription complex, CDH1L, as an inhibitor target, reversing EMT in CRC both in vitro and in vivo. Furthermore, the team has validated that lead CHD1L inhibitors synergize with CRC standard of care chemotherapy (e.g. FOLFIRI) significantly improving the potency, overcoming MDR. Therefore, CHD1L inhibitors have significant potential as drug therapies to sensitize cancer to conventional chemotherapy while inhibiting metastasis in CRC and other types of cancer.
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