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Last Updated: 04/29/22

2021 Translational Research Advances

[+] Ovarian

Robert C. Bast, Jr., MD, & Anil Sood, MD - The University of Texas MD Anderson Cancer Center Ovarian Cancer SPORE

A Novel Salt Inducible Kinase 2 Inhibitor, ARN-3261, Sensitizes Ovarian Cancer Cell Lines and Xenografts to Carboplatin

The salt-induced kinase 2 (SIK2) inhibitor, ARN-3261, increases carboplatin's ability to kill ovarian cancer cells grown in culture and in immunocompromised mice. Evidence indicates that ARN-3261 increases DNA damage and decreasing levels of survivin, a protein that protects cancer cells from programmed cell death. Results support the clinical evaluation of ARN-3261 for patients with advanced stage disease.

Citation:
Fan D, Yang H, Mao W, Rask PJ, Pang L, Xu C, Vankayalapat H, Ahmed AA, Bast RC Jr, Lu Z. A Novel Salt Inducible Kinase 2 Inhibitor, ARN-3261, Sensitizes Ovarian Cancer Cell Lines and Xenografts to Carboplatin. Cancers (Basel). 2021 Jan 25;13(3):446. doi: 10.3390/cancers13030446. PMCID: PMC7865895. PMID: 33503955

[+] Liver

Mark McNiven, PhD, & Lewis Roberts, MB, ChB, PhD - Mayo Clinic Hepatobiliary SPORE

Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy

The investigators have conducted clinical trials for hepatocellular carcinoma and other cancers that involve oncolytic vesicular stomatitis virus (VSV) expressing interferon beta as a therapeutic approach. Some patients have initial responses followed by aggressive relapse due to a point mutation (P5S) arising in the RNA-binding CSDE1 protein, a cellular co-factor for VSV replication. After this mutation arises, VSV adaptation eventually occurs via the appearance of a compensatory mutation in VSV itself. Interestingly, the investigators found the CSDE1P5S contains a neo-epitope that is recognized by non-tolerized T cells and have shown using mouse models that vaccination to raise an immune response against this neo-epitope can prevent tumor escape and relapse.

Citation:
Kottke T, Tonne J, Evgin L, Driscoll CB, van Vloten J, Jennings VA, Huff AL, Zell B, Thompson JM, Wongthida P, Pulido J, Schuelke MR, Samson A, Selby P, Ilett E, McNiven M, Roberts LR, Borad MJ, Pandha H, Harrington K, Melcher A, Vile RG. Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy. Nat Commun. 2021 Mar 26;12(1):1930. doi: 10.1038/s41467-021-22115-1. PMCID: PMC7997928. PMID: 33772027