May 10 2024Oncoscience A new editorial paper was published in Oncoscience on April 25, 2024, entitled, "Therapeutic opportunities for hypermutated urothelial carcinomas beyond immunotherapy."
In this new editorial, researcher Ioannis A. Voutsadakis from Sault Area Hospital and Northern Ontario School of Medicine discusses tumor mutation burden -;a novel clinical biomarker for prediction of checkpoint inhibitor immunotherapy response across cancers. High TMB has been used as a tumor agnostic indication for treatment with the PD-1 inhibitor pembrolizumab.
"However, both biomarkers are imperfect and not all cancers with high TMB or MSI phenotype respond to immunotherapy." The reason for this phenomenon may relate to additional alterations present in some tumors with high TMB or may be due to differences in the immune environment of diverse cancers. Conversely, some tumors with no MMR alterations have high TMB, and their hypermutability, which is due to other defects, such as pathogenic proofreading polymerase epsilon mutations, may still lead to immunotherapy sensitivity. A sub-set of urothelial carcinomas possess a high TMB.
"Combinatorial approaches based on immunotherapy and targeting additional molecular defects, that are present in urothelial carcinomas, hold the hope for successful therapy of the sub-set of immune checkpoint inhibitor resistant urothelial carcinomas with high TMB and of urothelial carcinomas with low TMB."Journal reference:Voutsadakis, I. A. . Therapeutic opportunities for hypermutated urothelial carcinomas beyond immunotherapy. Oncoscience. doi.org/10.18632/oncoscience.596.