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Researchers design drug to restore cell suicide in HPV-related head and neck cancer
Date:4/8/2013

the function of the p53 "tumor-suppressor" gene and triggers the death of the cancer cells.

"Our study revealed a new mechanism for p53 inactivation in HPV-positive head and neck cancer, and this allowed us to develop an agent that disrupts that interaction and reactivates p53 in HPV-positive head and neck cancer," Pan says. "Our pre-clinical studies show CH1iB can reactivate p53 and eliminate HPV-positive head and neck cancer cells."

Pan notes that the standard of care for HPV-positive head and neck cancer uses high-dose cis-platinum, a chemotherapy drug that causes serious side effects that are difficult for patients to tolerate. The drug's toxicity raises the need for safer therapy, and, although further testing is necessary, combining CH1iB with a low dose of cis-platinum might one day provide an alternative.

For this study, Pan and his colleagues used high-risk HPV-positive head and neck squamous cell carcinoma cells. Key technical findings include:

  • The small-molecule inhibitor CH1iB inhibits the binding of the HPV E6 protein with the p300 cell protein;

  • The binding of the CH1iB inhibitor with p300 reactivated p53 and dramatically potentiated the efficacy of cis-platinum in HPV-positive head and neck cancer cells.

  • The combination of CH1iB and cis-platinum eliminated 91 percent of HPV16-positive head and neck cancer cells; it also increased apoptosis by 984 percent and 443 percent compared with CH1iB and cis-platinum respectively alone.

"These results suggest that fewer cycles or a tapered dose of cis-platinum, along with a CH1 inhibitor, might be sufficient to effectively manage HPV-positive head and neck cancer patients and offer a better toxicity profile," Pan says.

"Taken together, our data suggest that we've discovered a novel approach for reactivating the p53 gene in HPV-positive head and neck cancer that may translate to other HPV-positive carcinomas."


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Contact: Darrell E. Ward
darrell.ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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