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Mayo Clinic and the National Cancer Institute collaborate to develop and study cancer models of key tumourigenesis pathway involved in drug resistance

The National Cancer Institute has 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 the characterization of SIAH2 (E3 ubiquitin ligase family) reagents, the development and validation of in vitro and in vivo cancer models, and 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 signalling of components in the mammalian RAS pathway is known to be a principle driving factor in many forms of cancer. Most notably, activating mutations in RAS genes themselves can result in aggressive tumour phenotypes that exhibit rapid proliferation and drug resistance by finding ‘workarounds’ through adjacent and downstream signalling pathways. The Mayo team found that through a novel approach of inhibiting the most downstream component (SIAH2) in the RAS signalling 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 tumours that exhibit K-RAS mutations. Discovering and developing alternative approaches to curb excessive RAS signalling, 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 signalling in several forms of rapidly progressing cancers is intriguing, and opens a promising gateway for therapeutic intervention,’ said Dr Serguei Kozlov of SAIC-Frederick. ‘We look forward to a close collaboration with our colleagues at the Mayo Clinic.’

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