PARP-Targeted Auger Therapy in p53 Mutant Colon Cancer Xenograft Mouse Models.

ABSTRACT: Despite Auger electrons being highly appealing due to their short-range and high linear energy transfer to surrounding tissues, the progress in the field has been limited due to the challenge in delivering a therapeutic dose within the close proximity of cancer cell's DNA. Here, we demonstrate that the PARP inhibitor ¹²³I-MAPi is a viable agent for the systemic administration and treatment of p53 mutant cancers. Significantly, minimal off-site toxicity was observed in mice administered with up to 74 MBq of ¹²⁷I-PARPi. Taken together, these results lay the foundation for future clinical evaluation and broader preclinical investigations. By harnessing the scaffold of the PARP inhibitor Olaparib, we were able to deliver therapeutic levels of Auger radiation to the site o

SUBMITTER: Wilson T 

PROVIDER: S-EPMC8686831 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature