Leukemia Inhibitory Factor Potential 'Druggable' Target in Pancreatic Cancer

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(ChemotherapyAdvisor) – Leukemia inhibitory factor plays an essential role in the properties of K-Ras-induced pancreatic cancer stem cells, “and may serve as a novel therapeutic target to eradicate pancreatic cancers with K-Ras activations,” investigators concluded in a June 19 presentation at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, Lake Tahoe, NV.

Although activating mutations of K-Ras occur in more than 90% of pancreatic cancers, developing specific approaches to target oncogenic K-Ras have been difficult, noted Man-Tzu Wang, PhD, at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. Therefore, identifying essential factor(s) for K-Ras-mediated malignancy “may provide an alternative way to block this ‘undruggable' oncogene,” he added.

Using human pancreatic cancer cell lines and mouse fibroblasts and pancreatic cancer cells, the investigators found that K-ras caused cells to acquire and maintain stem cell-like properties. “Whole genome microarray analyses revealed oncogenic K-Ras specifically up-regulated the expressions of multiple stem cell-related factors at the RNA level,” Dr. Wang noted. “Among these genes, leukemia inhibitory factor showed the greatest increase in K-RasV12-transformed cells (log-fold change=2.29749) when compared to H-RasV12-transformed cells.”

Specifically, they identified the stem cell regulatory chemokine, leukemia inhibitory factor, “as a downstream effector essential for K-Ras-medicated stemness in pancreatic cancer cells.” Unlike K-ras, leukemia inhibitory factor has the potential of being “druggable”—although no agents are currently available—making it a potential treatment target.

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