HOUSTON ― The University of Texas MD Anderson Cancer Center‘s Research Highlights provides a glimpse into recent basic, translational and clinical cancer research from MD Anderson experts. Current advances include using a CRISPR screen to identify targets for improved chemotherapy responses, the potential of glutaminase inhibitors as novel treatments in renal cell carcinoma, engineered tumor-infiltrating lymphocytes to overcome immune suppression in ovarian cancer, oncolytic viruses to improve responses in glioblastoma, combination therapy options for KRAS/NRAS-mutant colorectal cancer, and a new treatment target for a subtype of myelodysplastic syndromes.
CRISPR screen identifies new target to enhance benefits from certain chemotherapies
During DNA replication, topoisomerase proteins (TOPs) play the critical role of making temporary DNA-strand breaks so they can be untangled and made accessible to the replication machinery. Some chemotherapies, such as camptothecin, work by trapping TOPs on the DNA, causing sustained breaks and cell death. The TDP1 protein can help repair this damage, but it is not clear what other players may be involved in this process. A new study led by Huimin Zhang, Ph.D., Yun Xiong, Ph.D., and Junjie Chen, Ph.D., used a whole-genome CRISPR screen to identify MUS81 as a key protein in repairing damage from topoisomerase 1 (TOP1) in the absence of TDP1. They clarified the mechanism for MUS81’s activity and showed that loss of both TDP1 and MUS81 enhanced cancer cell sensitivity to camptothecin. These findings suggest that MUS81 could be an alternate target to improve activity of certain cancer therapies. Learn more in Nature Communications.
Drug combination improves progression-free survival in patients with renal cell carcinoma
Renal cell carcinoma (RCC) tumors generally display specific genetic alterations that cause cancer cells to increase metabolism of glutamine. Dual targeting of glucose and glutamine metabolism by the mTOR inhibitor everolimus, plus the glutaminase inhibitor telaglenastat, showed preclinical synergistic anticancer effects. The Phase II ENTRATA study, led by Nizar Tannir, M.D.