A preclinical platform for assessing antitumor effects and systemic toxicities of cancer drug targets.

ABSTRACT: Anticancer drug development campaigns often fail due to an incomplete understanding of the therapeutic index differentiating the efficacy of the agent against the cancer and its on-target toxicities to the host. To address this issue, we established a versatile preclinical platform in which genetically defined cancers are produced using somatic tissue engineering in transgenic mice harboring a doxycycline-inducible short hairpin RNA against the target of interest. In this system, target inhibition is achieved by the addition of doxycycline, enabling simultaneous assessment of efficacy and toxicity in the same animal. As proof of concept, we focused on CDK9—a cancer target whose clinical development has been hampered by compounds with poorly understood target specificity and unacceptable to

SUBMITTER: Li X 

PROVIDER: S-EPMC9169916 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature