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New target: Researchers identify pancreatic cancer resistance mechanism
Date:6/19/2014

Pancreatic cancer tumors addicted to mutant Kras signaling for their growth and progression have a ready-made substitute to tap if they're ever forced to go cold-turkey on the mutant oncogene, scientists at The University of Texas MD Anderson Cancer Center report in the journal Cell.

When researchers dialed up mutant Kras to spur pancreatic cancer growth in mice, and then shut it down, a group of recurrent tumors grew back independently of mutant Kras, reliant on a different oncogene.

"There's a great deal of effort under way trying to find ways to target Kras or some of the downstream targets that it activates," said co-lead author Haoqiang Ying, Ph.D., assistant professor of Molecular and Cellular Oncology. "It's important to understand how Kras-dependent tumors might evolve in response to targeted therapy."

The team found that some recurrent tumors were completely independent of mutant Kras and instead relied on signaling through another known oncogene called Yap1.

In addition to discovering a resistance mechanism for Kras-dependent tumors, the team found tumors dependent on Yap1 resemble a specific type of pancreatic tumor that provides a poor prognosis for patients who have it.

"Pancreas cancer remains an intractable disease with limited therapeutic options," said senior author Ron DePinho, M.D., president and professor of Cancer Biology. "Identifying and validating key targets in faithful model systems represents a critical first step in ultimately providing our patients with meaningful therapies."

Pancreatic ductal adenocarcinoma is one of the most lethal of cancers, with only 6.7 percent of patients surviving for five years. An estimated 46,420 new cases will be diagnosed in 2014, and approximately 39,590 people will die of the disease, according to the National Cancer Institute.

Mutations that activate Kras are present in the majority of human pancreatic cancer cases. Mou
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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