PHILADELPHIA (July 6, 2016) – The protein coding gene ERC33-MYC has been identified as a target in pancreatic cancer by researchers from Fox Chase Cancer Center - Temple Health.
Researchers developed a panel of new physiological models for the study of pancreatic ductal adenocarcinomas (PDAC), the most common type of malignancy in the pancreas and found that subset of pancreatic cells in the carcinoma tumors were particularly sensitive to the reaction of the drug triptolide.
“We found that a subset of MYC-amplified carcinomas are exquisitely sensitive to the drug,” said senior study author Igor Astsaturov, MD, PhD, a medical oncologist at Fox Chase. “Our results will help develop the new class of drugs targeting oncogenic transcription in pancreatic cancer that are currently in clinical trials including a drug called Minnelide.”
Developing a panel of new physiological models, scientists expanded surgical PDAC tumor samples using short-term culture conditional reprogramming with the Rho kinase inhibitor Y-27632 and creating matched patient-derived xenografts (PDX). These were then evaluated for sensitivity to a large panel of clinical agents, where researchers found that triptolide was the most consistently effective in causing prolonged, complete regression in multiple PDX models.
The paper detailing their work was published in Clinical Cancer Research, a publication of the American Association of Cancer Research, on July 6.
“The most difficult problem pancreatic cancer patients face is that the number of active drugs is very limited. Our work cleared the deck for researchers and clinicians to demonstrate that most existing therapeutics are very limited in their activity against pancreatic cancer.” said Astsaturov. “Using a chemical screening approach, we identified ERCC3 as a new target for pancreatic cancer and demonstrated the effects are extremely strong in a molecularly defined subset of pancreatic cancers.”