Pancreatic Cancer

Administration of the EGLN inhibitor FG-4592 prior to ablative radiotherapy provided protection against fatal gastrointestinal bleeding and improved survival in a mouse model of unresectable pancreatic cancer. Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research Author: Cullen Taniguchi, MD, PhD, assistant professor of radiation oncology at The University of Texas MD Anderson Cancer Center.
Background: Surgery is require for the curative treatment of pancreatic cancer, yet the majority of patients with this disease have unresectable tumors, said Taniguchi. While radiation therapy may be a future alternative to surgery in this patient population, the require dose of radiation to effectively treat the disease can damage the neighboring organs, which can lead to gastrointestinal bleeding and even death, he explained.

Possible to protect the bowels

This study was conduct to understand if it was possible to protect the bowels from radiation damage in order to give enough radiation to effectively treat unresectable pancreatic cancer,” he said. Hypoxic cells induce a powerful regenerative response, resulting in the protection of tissue, Taniguchi said. “Inhibition of EGLN mimics hypoxia, allowing us to take advantage of the healing response of this phenomenon without actually depriving the cell of oxygen,” he explained.
How the Study Was Conduct and Results; Tumor hypoxia is a feature of many cancerous cells that can lead to disease progression and metastasis and is especially prevalent in pancreatic cancer, Taniguchi noted. The researchers find that murine pancreatic tumors were already highly hypoxic and adding FG-4592 did not induce further hypoxia; however, in normal murine tissues; which are not hypoxic; so adding the EGLN inhibitor effectively mimicked hypoxia and protect the tissue.

To determine if administration of FG-4592 improve survival following ablative radiation therapy; so the researchers assign 70 mice bearing spontaneous; so palpable pancreatic tumors one of four treatments: vehicle only, FG-4592 only, vehicle plus radiotherapy, and FG-4592 plus radiotherapy. FG-4592 and vehicle were administer orally; also radiotherapy treatments consist of 15 fractions to a limit tumor field totaling 75 Gray.

Radiotherapy with prior radioprotection

Overall, treat with radiotherapy with prior radio protection via FG-4592 had the highest median; hence overall survival (43 days); no gastrointestinal bleeding was observe. Hence treat with radiotherapy without radio protection decrease median overall survival (36 days); also fatal gastrointestinal bleeding was observe in 56% of mice in this cohort. The difference in overall survival between these two groups was statistically significant.
Among mice that did not receive radiotherapy, treatment with FG-4592 increase the median; so overall survival compare to vehicle alone (29 days versus nine days, respectively). Author’s Comments: “The fact that treatment with FG-4592 alone increase survival; hence in them harboring pancreatic cancer was a surprising finding,” said Taniguchi. “They are actively investigating this result, and one preliminary hypothesis; hence is that EGLN inhibition may modulate the immune system and contribute to this therapeutic effect,” he added.
“Our proof-of-concept study illustrates that higher doses of radiation therapy; hence can improve outcomes in unresectable pancreatic cancer as long as treatment toxicity is reduce with a radiation protector,” said Taniguchi. “As toxicity is a major limiting factor of cancer treatment; so protecting normal tissues from radiation damage is an important concept; hence in the field of oncology that warrants additional attention,” he noted.