Clinically Relevant JAK Inhibitors Battle Colon Cancer in Pre-Clinical Studies

Clinically Relevant JAK Inhibitors Battle Colon Cancer in Pre-Clinical Studies

shutterstock_8880973An effective new therapy used against bowel cancer tumors may be quickly propelled from laboratory testing to clinical trials for subsequent approval. The therapy, already in use to treat psoriasis, arthritis, and myelofibrosis, is known as a JAK inhibitor and could be effective against 80% of colon tumors.

“About 17,000 people are diagnosed with bowel cancer every year and about 4,000 people die, so we are really crying out for new ways to tackle this disease,” said Dr. Toby Phesse of the Walter and Eliza Hall Institute of Medical Research in Melbourne, underscoring the importance of the study reported by Daily Mail Australia. Dr. Phesse was joined by colleagues Dr. Michael Buchert and Associate Professor Matthias Ernst to make this new discovery.

Motivation for the study came from the fact that common cancer treatments modulate the Wnt signaling pathway. “We have known for many years that Wnt signaling is mutated in around 80% of colon tumors,” Dr. Phesse added. “However, this pathway is also very important for the health of the normal cells in the intestine, and therefore targeting the Wnt pathway directly poses considerable challenges as you risk effecting the normal cells of the intestine and therefor inducing severe side effects.”

Dr. Phesse chose to find an alternative pathway and landed on the JAK signaling pathway. JAK inhibitors exist in the clinic already, but rather than use them as therapies for arthritis, Dr. Phesse applied the inhibitors to colon tumors, of which 80% responded, and saw no response from normal cells.

“None of the mice used in the models lost any weight, suggesting they were healthy and could tolerate the drug very well,” said Dr. Phesse. The JAK inhibitors stopped only cancer cell growth, preventing new tumors from developing and preserving the normal function of the intestine.

An exciting part of the discovery, according to Dr. Phesse, is the existence of JAK inhibitors in the clinic. “This means it is going to speed up the clinical trials process,” predicted Dr. Phesse. “We hope that this will enable our research to rapidly reach clinical trials for bowel cancer patients and deliver benefits in the near future,”added Dr. Buchert.

There is currently only one clinical trial listed for JAK inhibitors in a context somewhat related to colon cancer. Pfizer is sponsoring a clinical trial of the drug CP690, 550 to investigate the effects of the drug on ulcerative colitis remission. This may soon change if Dr. Phesse’s and colleagues’ continued efforts lead to further positive data regarding JAK inhibition in colon cancer tumor cells.

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Maureen Newman is a science columnist for Pulmonary Hypertension News. She is currently a PhD student studying biomedical engineering at University of Rochester, working towards a career of research in biomaterials for drug delivery and regenerative medicine. She is an integral part of Dr. Danielle Benoit's laboratory, where she is investigating bone-homing therapeutics for osteoporosis treatment.

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