skip to Main Content

Key Protein A Possible New Target in the Treatment of Pancreatic Cancer Pancreatic Cancer Collective Supports Important Study Published in Nature

Key Protein A Possible New Target in the Treatment of Pancreatic Cancer Pancreatic Cancer Collective Supports Important Study Published in Nature
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 on April 17, 2019, 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.

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.


Back To Top