Project title: Comprehensive Cancer Center of Taipei Medical University Program title: Investigation of HMGA2 role in the pathogenesis, prevention, diagnostic biomarkers and novel therapeutic drugs
Identification of Novel Therapeutic Compounds for Colorectal Cancer
Kai-Cheng Hsu , Ya-Wen Cheng, Tsui-Chin Huang, Kuen-Haur Lee, Pei-Ming Yang, Er-Chieh Cho
許凱程 , 鄭雅文, 黃翠琴, 李崑豪, 楊培銘, 卓爾婕
Research Team of Prevention and Therapy of Colorectal Cancer at Taipei Medical University
Colorectal cancer (CRC) is one of the main causes of cancer death in the world. CRC treatment is often limited by the development of drug resistance. Our team previously found that HMGA2 is highly expressed in CRC patients and is associated with drug resistance and poor clinical outcome. In this project, we established a HMGA2-mediated interaction network and identified novel inhibitors for proteins in the network. In addition, we identified highly overexpressed proteins in CRC as new therapeutic targets. Structure-based virtual screening was performed to identify potential inhibitors for each protein. In total, we discovered 14 novel compounds that inhibited the growth of CRC cell lines with IC50 values of <10µM. Enzyme-based assays showed that the compounds inhibited proteins associated with HMGA2 or proteins overexpressed in CRC, such as PDGFRB, MKNK2, ABL1, PDGFRA, RSK2, and AURKB. These inhibitors have the potential to be developed as therapeutic drugs for CRC.