image: Pancreatic Cancer Collective-funded research (Lustgarten Foundation and Stand Up To Cancer) from Dr. Tony Hunter (Salk Institute) and the SU2C-CRUK-Lustgarten Pancreatic Cancer Dream Team has found the presence of a key protein (Leukemia Inhibitory Factor or LIF) in PDAC microenvironment may be an exploitable treatment target to slow tumor progression or metastasis and may lead to the development of new targeted strategies for pancreatic cancer therapy. view more
Credit: Stand Up To Cancer, Lustgarten Foundation
WOODBURY, N.Y., April 17, 2019 -- Pancreatic cancer can be difficult to treat and often responds poorly to chemotherapy due to the presence of tumor cells located within the dense protective tissue, called the stroma. Research funded by the Pancreatic Cancer Collective, a partnership between Lustgarten Foundation and Stand Up To Cancer and guided by Dr. Tony Hunter at the Salk Institute was published today in Nature and has found that the interaction between pancreatic stellate cells (PSC's) and pancreatic cancer cells could be "exploitable" due to the presence of a key protein and lead to the development of new targeted strategies for pancreatic cancer therapy.
The tumor microenvironment, which exists within the stroma, contains many cells, but predominantly consists of PSCs, which interact with pancreatic cancer cells and lead to tumor progression and metastasis. Dr. Hunter's research focuses on further examining the interplay between the PSCs and pancreatic cancer cells and the key protein known as Leukemia Inhibitory Factor (LIF), which is responsible for the activation of PSCs in the cancer cells.
In a normal pancreas LIF protein levels were undetectable but were dramatically elevated in the tissue of patients with Pancreatic Ductal Adenocarcinoma (PDAC). In both mouse and human pancreatic cancer tissue, the level of LIF was elevated in activated PCS cells and indicate that PSCs are responsible for the production of LIF.
"If we can block LIF pharmacologically or genetically, then we may be able slow down a tumor's progression and metastasis making it easier to administer chemotherapy and prolong survival," said Dr. Hunter.
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This research was supported by the Stand Up To Cancer Pancreatic Cancer Dream Team, and the SU2C-Cancer Research UK-Lustgarten Foundation Pancreatic Cancer Dream Team. Additional authors on this paper include Dream Teams Leader Daniel Von Hoff, MD and Team Investigator Erkut Borazanci, MD (The Translational Genomics Research Institute, a division of City of Hope; and Honor Health); and Dream Team Co-leader Ronald M. Evans, PhD and Team Investigator Michael Downes. PhD (Salk Institute for Biological Studies); and Team Investigator Tannishtha Reya, PhD (UC San Diego School of Medicine).
Dr. Hunter and his team have found that the level of LIF in the blood determines how well a patient will respond to treatment. Patients with high LIF in the blood will have a poorer response to chemotherapy treatment and may have further disease progression than a patient who has a lower LIF level. His research has found that in mice deficient in LIF, pancreatic cancer cells in tumors were significantly smaller and the tumor was further reduced in size when treated with chemotherapy, suggesting LIF plays a role in chemotherapy resistance.
This research suggests that the presence of high levels of LIF correlates with disease progression and the tumor response to chemotherapy revealing that it could be useful as a biomarker to indicate a patient's therapeutic response.
About the Pancreatic Cancer Collective
The Pancreatic Cancer Collective is an initiative of the Lustgarten Foundation and Stand Up To Cancer to improve pancreatic cancer patient outcomes. Together, these leading cancer research organizations will attract new collaborators; improve diagnosis of pancreatic cancer using big data; find new treatments for pancreatic cancer; and support the next generation of pancreatic cancer investigators. Engaging thought leaders, researchers, institutions, and companies, the Collective will innovate and accelerate research on the edge of science. For more information, visit http://www.pancreaticcancercollective.org
About Lustgarten Foundation
Lustgarten Foundation is America's largest private funder of pancreatic cancer research. Based in Woodbury, N.Y., the Foundation supports research to find a cure for pancreatic cancer, facilitates dialogue within the medical and scientific community, and educates the public about the disease through awareness campaigns and fundraising events. Since its inception, Lustgarten Foundation has directed $154 million to research and assembled the best scientific minds with the hope that one day, a cure can be found. Thanks to separate funding to support administrative expenses, 100% of your donation goes directly to pancreatic cancer research. For more information, visit http://www.lustgarten.org.
About Stand Up To Cancer
Stand Up To Cancer (SU2C) raises funds to accelerate the pace of research to get new therapies to patients quickly and save lives now. SU2C, a division of the Entertainment Industry Foundation (EIF), a 501(c)(3) charitable organization, was established in 2008 by film and media leaders who utilize the industry's resources to engage the public in supporting a new, collaborative model of cancer research, and to increase awareness about cancer prevention as well as progress being made in the fight against the disease. As SU2C's scientific partner, the American Association for Cancer Research (AACR) and a Scientific Advisory Committee led by Nobel Laureate Phillip A. Sharp, PhD, conduct rigorous, competitive review processes to identify the best research proposals to recommend for funding, oversee grants administration, and provide expert review of research progress.
Current members of the SU2C Council of Founders and Advisors (CFA) include Katie Couric, Sherry Lansing, Lisa Paulsen, Rusty Robertson, Sue Schwartz, Pamela Oas Williams, Ellen Ziffren, and Kathleen Lobb. The late Laura Ziskin and the late Noreen Fraser are also co-founders. Sung Poblete, PhD, RN, has served as SU2C's president and CEO since 2011.
Journal
Nature