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Inactive TSPAN6 protein could make CRC drugs less effective

Tue, 09/14/2021 - 09:14
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Scientists at the University of Birmingham have discovered a previously unknown pathway that prevents specific drugs from working in patients with colorectal cancer. The research findings could pave the way for increasing the number of bowel cancer patients who can be successfully treated. The findings were published in the paper, ‘Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer’, published in the Proceedings of the National Academy of Sciences.

"About 60% of bowel cancers are sensitive to drugs called anti-EGFR inhibitors which work by blocking a key pathway in these cancers,” said co-senior author, Professor Andrew Beggs, Professor of Cancer Genetics & Surgery at the University of Birmingham. “However, despite this, in cancers that should be sensitive to them, these drugs only work in patients about 50% of the time.”

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

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

The researchers are now set to undertake a clinical trial of using this marker to better identify patients for anti-EGFR treatment.

"This is the first time a tetraspanin protein has been shown to be directly involved with bowel cancer,” concluded the study’s first author, Dr Regina Andrijes, a Postdoctoral Fellow at the University of Birmingham. “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."

The study was carried out in collaboration with University Hospitals Birmingham NHS Foundation Trust, Semmelweis University in Hungary and Assiut University in Egypt.

To access this paper, please click here