Vera Bradley Foundation Professor of Breast Cancer Innovation
Department of Medical and Molecular Genetics
Simon Cancer Center
Treating human cancers with heterozygous loss of chromosome 17p
TP53 is frequently inactivated by mutation or deletion in a majority of human tumors. A tremendous effort has been made to restore p53 activity in cancer therapies. However, no effective p53-based therapy has been successfully translated into clinical cancer treatment due to the complexity of p53 signaling. My recent work demonstrated that genomic deletion of TP53 frequently encompasses the neighboring essential gene POLR2A in Chr17p, rendering cancer cells with heterozygous TP53 deletion vulnerable to further suppression of POLR2A. Suppression of POLR2A by α-amanitin-based antibody drug conjugates (ADCs) selectively inhibits proliferation, survival and tumorigenic potential of cancer cells with 17p loss. The clinical trial based on this work will be initiated in 2020 by Heidelberg Pharma, a long-standing collaborator for development of α-amanitin-based ADCs. Additionally, I have also identified a number of therapeutic vulnerabilities from various types of human cancer, including ovarian cancer, Ewing’s sarcoma, urinary bladder cancer and triple negative breast cancer.