|Awarded On||August 18, 2021|
|Title||Identification of collateral lethal and synthetic lethal targets in pancreatic and colorectal cancers|
|Award Mechanism||High Impact/High Risk|
|Institution/Organization||The University of Texas M.D. Anderson Cancer Center|
|Principal Investigator/Program Director||Ronald DePinho|
|Cancer Sites||Colorectal, Pancreas|
Pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) are among the leading cancer killers with 47,000 deaths from PDAC and 53,000 deaths from metastatic CRC estimated in US 2020. PDAC and CRC genomes frequently contain deletions of tumor suppressor genes, including SMAD4 which is deleted in nearly 33% of PDAC cases and 10% of advanced CRC. When cancer cells sustain deletion of SMAD4, nearby genes that may play essential cell functions are invariably co-deleted. Cancer cells survive these co-deletions due to the presence of functionally redundant family members (known as paralogs) which reside elsewhere in the genome. We hypothesized that inhibiting the non-deleted paralogs can...