In a study that will appear today in the print edition of Nature and received advanced publication online earlier this month, the Dream Team reported finding increased expression of WNT2, a member of a known family of oncogenes, in CTCs from mouse models of pancreatic cancer and from human patients.
The SU2C Dream Team “Bioengineering and Clinical Applications of Circulating Tumor Cell Chip” is led by Daniel A. Haber, M.D., Ph.D., director of the Massachusetts General Hospital (MGH) Cancer Center, and Mehmet Toner, Ph.D., director of the Massachusetts General Hospital Center for Bioengineering in Medicine in Boston.
“Studying cancer cells as they circulate in the blood is a critical way to figure out how cancer spreads and finding ways to try to block that,” said Haber. “It has taken a real partnership between engineers, biologists and clinicians to develop the technology to fish out these incredibly rare cells in the blood, study them with molecular tools and start applying these findings toward new treatments.”
Haber and colleagues used the second-generation version of the CTC chip – developed with support from the SU2C grant – to isolate CTCs from mice that were genetically engineered to develop pancreatic cancer. They then compared gene expression between the CTCs in the blood and cancer cells within the pancreatic tumor, to look for genes that helped tumor cells invade into the bloodstream. The team was able to identify several genes that were expressed at higher levels in the CTCs. From this group of genes, WNT2 (a member of a signaling pathway known for its role in embryogenesis and cancer) was selected for further investigation. Results showed that WNT2 was highly expressed in CTCs and metastases. These findings were in contrast to primary tumors, in which WNT2 was rarely expressed.
Through further studies, the Dream Team ultimately showed that WNT2 might be responsible for the CTC’s ability to escape “anoikis” – one of the body’s normal mechanisms to eliminate these cells as they circulate in the blood. If CTCs are not eliminated, they have an increased chance of establishing metastases.
The team also identified a drug that blocks a step in the WNT2 pathway, thereby suppressing the ability of CTCs to survive in the bloodstream. This drug is not available for clinical use and further studies would be needed to test its efficacy in patients with pancreatic cancer. While most of the work was performed using a mouse model of pancreatic cancer, the team found that similar mechanisms appear to operate in CTCs from patients with pancreatic cancer.
This study sheds new light on how pancreatic cancer cells may metastasize, and identifies a potential drug target for interrupting the WNT pathway and limiting the chance for metastases to spread to other organs.
About Stand Up To Cancer
Stand Up To Cancer (SU2C) – a program of the Entertainment Industry Foundation (EIF), a 501(c) (3) charitable organization – raises funds to accelerate the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. SU2C facilitates collaboration among the best and the brightest in the cancer research community. The American Association for Cancer Research (AACR) and a Scientific Advisory Committee conduct rigorous, competitive review processes through which SU2C’s grantees are selected. By galvanizing the entertainment industry, SU2C generates awareness and builds grassroots support for this new approach to ending cancer.
Stand Up To Cancer was founded by a group of media, entertainment and philanthropic leaders whose lives have been affected by cancer in significant ways. Members of SU2C’s Executive Leadership Council include Cancer Advocate and Television Journalist Katie Couric; Sherry Lansing, chairperson of the Entertainment Industry Foundation’s (EIF) Board of Directors and founder of the Sherry Lansing Foundation; EIF President and CEO Lisa Paulsen; EIF Senior Vice President Kathleen Lobb; Rusty Robertson and Sue Schwartz of the Robertson Schwartz Agency; Pamela Oas Williams, President of Laura Ziskin Productions; and nonprofit executive Ellen Ziffren. The late Laura Ziskin, a legendary film producer who executive produced the 2008 and 2010 SU2C telecasts, was also a member of the Executive Leadership Committee. SU2C was formally launched on May 27, 2008. Sung Poblete, Ph.D, R.N., has served as SU2C’s president and CEO since 2011.
For more information, visit www.standup2cancer.org
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.