Blocking the Pathway to Pancreatic Cancer

Pancreatic cancer tumors reduced when liver x receptors activated

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Bet you didn't know that heart disease and pancreatic cancer have something in common. Indeed they do - they share a link with genetic pathways that control both cholesterol and a system by which cells communicate - the Hedgehog pathway.

Researchers have discovered that targeting this pathway may boost the cancer-killing capabilities of standard chemotherapy drugs.

This work may produce new drugs or novel combinations of agents that attack and destroy tumors.

"Talk to your oncologist about the latest cancer research."

Scientists at Johns Hopkins are leading the way in this research which focuses on the Hedgehog pathway, which is known to trigger a number of different cancers. Five new drugs that target this pathway are currently being tested.

To search for new ways to go after the Hedgehog, William Matsui, M.D., Ph.D., professor at the Johns Hopkins Kimmel Cancer Center, partnered with UCLA biologist Farhad Parhami, Ph.D.

Parhami has found that so-called "liver x receptors" direct how cholesterol is distributed throughout the body. In the process, these receptors actually block the Hedgehog pathway.

Dr. Matsui says as a result of this finding, new drug therapies may be aimed at getting liver x receptors into action so they can block the menacing functions of the Hedgehog pathway.

"Activating liver x receptor could be an alternate target for blocking the Hedgehog pathway," says Dr. Matsui, who points out this is an unusual strategy. 

For this study, researchers treated mice with implanted human pancreatic tumors with a drug that activates liver x receptors along with gemcitabine, a chemotherapy agent.

While the receptor activator alone didn't have an effect, the two drugs working together shrank the tumors. The combination resulted in a five-fold reduction of Hedgehog pathway elements.

Dr. Matsui and Parhami are working with UCLA chemists Michael Jung and Frank Stappenbeck to develop new and more effective liver x receptor activators to target pancreatic cancer and other tumors associated with the Hedgehog pathway.

Research findings are considered preliminary before they are published in peer-reviewed journals.

Funding for the study was provided by the National Cancer Institute.

Reviewed by: 
Review Date: 
April 10, 2012
Last Updated:
April 11, 2012