Mismatch repair is considered a classic tumor suppressor, loss of which is common in nonpolyposis human colorectal cancer (HPNCC). We found that MSH2 and MSH6, two important proteins involved in mismatch repair, are highly elevated in basal-like breast cancer (BLBC) subtype and their expressions significantly correlate with shorter patient survival. We believe that this mismatch pathway could be important for BLBC progression and want to study their roles in BLBC. In collaboration with Maria Spies from Department of Biochemistry and Meng Wu from College of Pharmacy at University of Iowa, we are screening for small inhibitors for this pathway as well as compounds that would provide an effective treatment options for patients in conjunction with this inhibitor. Our goal is to open up a host of new therapeutic options, including anti-PD-1 immunotherapy1, as well as increase the efficacies of the current available treatment options for BLBC patients.
- Le et al. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jun 8. pii: eaan6733. doi: 10.1126/science.aan6733. [Epub ahead of print].