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12/8/09 - Mayo Clinic and the National Cancer Institute Collaborate to Develop and Study Cancer Models

Partnership to Develop and Study Cancer Models of Key Tumorigenesis Pathway Involved in Drug Resistance

The National Cancer Institute and its operations and technical-support contractor, SAIC-Frederick, Inc., have entered into a research-and-development collaboration with Mayo Clinic to expand on recent research discoveries at Mayo, where researchers have demonstrated the importance of a key protein involved in pancreatic and lung cancer.

The agreement is part of the National Cancer Institute’s Advanced Technology Partnerships Initiative, which aims to speed up the translation of basic research into technologies and treatments for patients with cancer and AIDS.

The collaboration will focus on characterization of SIAH2 (E3 ubiquitin ligase family) reagents, development, and validation of in-vitro and in-vivo cancer models, and on the study of SIAH2 as a potential drug target. The R&D will be conducted at NCI-Frederick’s Center for Advanced Preclinical Research (CAPR) by SAIC-Frederick.

Aberrant signaling of components in the mammalian RAS pathway is known to be a principal driving factor in many forms of cancer. Most notably, activating mutations in RAS genes themselves can result in aggressive tumor phenotypes that exhibit rapid proliferation and drug resistance — by finding “work-arounds” through adjacent and downstream signaling pathways. The Mayo team found that through a novel approach of inhibiting the most downstream component (SIAH2) in the RAS signaling pathway, programmed cell death, or apoptosis, increased, and cell proliferation was inhibited. This was true in several cancer types studied. The published findings were well-received by the cancer R&D community.

Many current targeted therapies for cancer do not work in tumors exhibiting K-RAS mutations. Discovering and developing alternative approaches to curb excessive RAS signaling, such as the SIAH2 project described above, have the potential to provide great clinical benefit to cancer patients in the future, through improved, targeted, and more durable therapies.

“The impact of SIAH2 ubiquitin ligase on modulating aberrant RAS signaling in several forms of rapidly progressing cancers is intriguing, and opens a promising gateway for therapeutic intervention,” said Serguei Kozlov, Ph.D. of SAIC-Frederick. “We look forward to a close collaboration with our colleagues at the Mayo Clinic.”

Information about the NCI’s Advanced Technology Partnerships Initiative can be found at ATPIhome.com