Large-scale Epigenomic Reprogramming Links Anabolic Glucose Metabolism to Distant Metastasis during the Evolution of Pancreatic Cancer Progression

Unmet Need

• Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer death in the western world by 2020. Subclonal populations that emerge and drive metastatic progression of the disease are associated with high mortality rates among patients. Blocking the tumorigenic potential of metastatic sites is key to improving current clinical outcomes. Epigenetic changes driving this disease were identified and targeted through inhibition of a key glucose metabolism pathway. This approach could represent a novel and effective therapeutic strategy for metastatic PDAC. Key features:Methods for identifying metastatic propensity in primary tumors
• Novel strategy targeting metastatic disease
• Achieved selective reversal o f disease-associated changes
• Blocked tumorigenic potential of distant metastatic sites

Technology Overview

During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, local-regional spread, distant metastasis, and patient death. Johns Hopkins researchers observed that epigenetic reprogramming was driven by a branch of anabolic glucose metabolism. Excitingly, the targeting of this branch yielded a selective reversal of reprogrammed chromatin and blocked tumorigenic potential of distant metastatic subclones. This invention constitutes a novel method of targeting the metastatic progression of highly fatal PDAC.

Stage of Development

Discovery. Looking for partners to develop and commercialize novel metastatic detection and therapeutic strategies for preventing, delaying, or reversing metastatic growth of PDAC.

Publication:

McDonald, Oliver G., et al. "Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis." Nature genetics 49.3 (2017): 367-376.

Issued Patents: US 11,795,510 and JP 7239468