Developing Zinc Metallochaperones as Mutant p53 targeted Anti-Cancer Drugs
The gene that encodes the transcription factor, p53 (TP53) is the most commonly mutated gene in human cancer for which no effective targeted anti-cancer drug exists. The majority of mutations in p53 are missense, which means that a single amino acid change produces a defective protein which can serve as a target for cancer drug development.
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Reversing the p53 Mutant Phenotype with a small molecule
Virtually all BRCA1 deficient breast cancers harbor mutations in TP53 suggesting that inactivation of p53 is a requirement for tumor progression. Our group along with the our collaborator, Dr. Shridar Ganesan (Rutgers Cancer Institute of New Jersey) was the first to demonstrate this dependency can be exploited therapeutically using Zinc Metallochaperones (ZMCs) to reactivate mutant p53 (PMID 30993195).
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Investigating the mechanisms of pancreatic cancer dormancy
The Carpizo lab is at the forefront of research in cancer dormancy having just recently produced the first mouse model of pancreatic cancer dormancy that mimics the biology of the resected patient (bioRxiv 2020.04.13.037374; doi: https://doi.org/10.1101/2020.04.13.037374). This model recapitulates the early and latent recurrent phenotypes seen in human patients following surgery.
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Investigating Netrin-1 as a novel therapeutic target in metastatic pancreatic cancer
Pancreatic cancer is a highly metastatic cancer. The majority of patients with pancreatic cancer are stage IV at the time of diagnosis and the majority of patients (>80%) who have early stage disease go on to suffer from metastatic relapse following curative intent surgery. Novel therapies that target the molecular mechanisms that govern pancreatic cancer metastasis are highly needed.
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