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Pathway discovered for bowel cancer drug failure

Tuesday September 14th 2021

A protein pathway prevents some bowel cancer drugs from working, researchers reported last night.

Researchers behind the study, which was published yesterday in the Proceedings of the National Academy of Sciences, say they hope finding the pathway, which involves a tetraspanin protein, will lead to an increase the number of bowel cancer patients who can be successfully treated.

The research, led by the University of Birmingham, studied 184 tumour samples and medical records of bowel cancer patients participating in the COIN trial, and involved research carried out in mice, cell cultures, and a laboratory model for pre-malignant colorectal cancer.

Co-senior author Dr Fedor Berditchevski, of the University of Birmingham, said: “Scientists have previously found that if bowel cancer patients have a mutation in a gene called RAS, the anti-EGFR inhibitors will not work.

“However, our research has now discovered a new pathway involving a tetraspanin protein called TSPAN6 that is frequently inactive in bowel cancer patients and this makes these drugs less effective.

“Crucially, our research also shows that if this pathway is active in a patient’s cancer, then the drug will work, irrespective of whether they have a mutation in RAS or not.”

First author Dr Regina Andrijes, a postdoctoral Fellow at the University of Birmingham, who worked with colleagues at University Hospitals Birmingham NHS Foundation Trust, Semmelweis University in Hungary, and Assiut University in Egypt, said it is the first time a tetraspanin protein has been shown to be directly involved with bowel cancer.

“Our research findings show that this new pathway could act as a biomarker for treatment with anti-EGFR drugs in bowel cancer, increasing a patient’s chance of survival and the number of patients who could benefit from these drugs who previously would not have,” she added.

A clinical trial to use this marker to better identify patients for anti-EGFR treatment is being planned.

Andrijes et al. Tetraspanin 6 (Tspan6) is a new regulator of carcinogenesis in colorectal cancer. PNAS 13 September 2021.

[COIN trial]

Tags: Cancer | Gastroenterology | Pharmaceuticals | UK News

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