New treatment options discovered for colorectal tumors

Scientists have discovered that an existing chemotherapy drug used to treat leukemia could prevent and control the growth of colorectal tumors. Their initial studies, conducted in mice, were described in a report in Science Translational Medicine (2015; doi:10.1126/scitranslmed.3010567).

Colorectal cancer is one of the three most common cancers worldwide. Almost 95% of colorectal cancers are from malignant tumors.

The research team, from Nanyang Technological University (NTU Singapore) and Sweden's Karolinska Institutet, found that imatinib, an enzyme blocker widely used to treat leukemia, works by blocking a signalling pathway related to a group of cell receptors called EphB. This means that when used to treat mice with colon tumors, it was able to halve the growth of tumors in the intestines.

The finding is also significant as currently there is no drug available to prevent the recurrence of tumors in the intestine after the cancerous tumors have been removed by surgery.

"Our work has important clinical implications, since imatinib is a potentially novel drug for the treatment of tumour formation and cancer progression in patients predisposed to develop colorectal cancer," said Professor Sven Pettersson, MD, PhD, professor of Metabolic Disease at NTU's Lee Kong Chian School of Medicine and senior principal investigator with the National Cancer Centre Singapore.

In their tests, imatinib was able to block tumor initiation at the stem cell level by half and significantly reduced tumor growth and proliferation.

"In mice which mimicked human colon cancer, imatinib was shown to prolong their life span," Parag Kundu, PhD, also of NTU. "The drug was also effective in increasing the survival of mice that had late-stage tumors and rectal bleeding."

The same effects were also shown when imatinib was tested on colon tumor tissues taken from human patients.

Colon cancer usually develops first as benign tumors, which when left untreated turn aggressive, and may spread to other parts of the body. The main treatment in the early stages of colon cancer is resection, where the affected section of the intestine is removed through surgery.

The scientists said these findings also suggest that short-term intermittent chemotherapies could be possible as a treatment model, as this would substantially reduce the side effects known to occur when imatinib is given for longer periods.

"Our findings provide experimental evidence that imatinib treatment did not interfere with the tumor suppressor function of EphB receptors," said Jonas Frisén, MD, PhD, Professor of Stem Cell Research at Karolinska Institutet, who co-supervised the study.

This is beneficial as EphB receptors also function to keep the tumor intact, which prevents cancerous cells from spreading to surrounding tissue should the tumor break apart.

The study was supported by NTU's Lee Kong Chian School of Medicine, the Singapore Millennium Foundation, the National Cancer Centre Singapore, the Swedish Research Council, the Swedish Cancer Society, Karolinska Institutet, the Tobias Foundation, the Knut and Alice Wallenberg Foundation, and the Torsten Söderberg Foundation.

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