Targeting DNA Repair to Drive Immune Responses: It's Time to Reconsider the Strategy for Clinical Translation.

ABSTRACT: PARP inhibition induces robust local and systemic antitumor immune responses and curative responses when combined with immune checkpoint blockade in many preclinical studies. However, the combination has not markedly improved antitumor effect compared with individual agents in clinical trials to date. We propose that the data from these trials indicate a lack of synergistic interaction of PARP inhibition and immune checkpoint blockade, with implications for reexamining our current strategies for clinical translation. As current mouse models do not recapitulate the genomic heterogeneity or tumor microenvironment of human cancers, better models are urgently needed. Tumor-extrinsic factors modulate immune checkpoint blockade response and they may be better assessed in early-phase clinical tri

SUBMITTER: Takahashi N 

PROVIDER: S-EPMC8283908 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature