Indian-US team identifies genetic target for treating colorectal cancer

Kolkata, Sep 7 (IANS) Making strides in the treatment of colorectal cancer (CRC), the third most common cancer in the world, a team of researchers from India and the US has identified a genetic target for potential drug therapy against the dreaded disease.

Also called colon, rectal or bowel cancer, CRC is the third most common cancer in men and the second in women worldwide.

“We have reported that the SPINK 1 gene is a potential therapeutic target in colorectal cancer (CRC),” Bushra Ateeq, lead author of the study and assistant professor, department of biological sciences and bioengineering at IIT-Kanpur, told IANS on the phone.

“In the light of increasing resistance to therapies (such as the anti-EGFR

therapy) against CRC, we feel that targeting SPINK1 protein may be a tenable treatment option in CRC patients,” Ateeq said.

According to the US National Institute of Health (NIH), about 132,700 new CRC cases are likely to be diagnosed this year, and 49,700 patients are estimated to succumb in the US alone.

The low incidence rates for India (4.2 and 3.2 per 100,000 in males and females)compared to developed nations, is largely attributed to a plant-based and anti-oxidant rich diet. But a steady increase in CRC cases has been noted due to urbanisation and lifestyle changes, including dietary habits.

Given the global implications, experts from the Indian Institute of Technology-Kanpur and Michigan Center for Translational Pathology at the University of Michigan embarked on a collaborative project to zero-in on the SPINK1 gene.

What makes this approach click?

Like most, this gene too serves as the blueprint of a protein.

In healthy individuals, this protein is secreted by pancreatic cells into the pancreatic juice and plays a protective role for the mucosal lining of the colon and gastrointestinal tract.

In contrast, during cancer progression (such as colon, lung, breast and prostate) SPINK1 is over-expressed, which means too much of the coded protein is produced.

“But the case is just opposite for metallothioneins (MT) – a group of small proteins that maintain a balanced environment inside the normal colon by protecting it against heavy metals and eliciting anti-inflammatory response,” Ateeq said.

However, the expression level of these small proteins was found to be down in CRC.

The scientists took advantage of this co-relation and discovered that the cancer cells’ sensitivity to drugs could be manipulated by altering the SPINK1 levels.

“When we targeted SPINK1 gene (as in making it inoperative as a coding agent), the SPINK1 protein levels went down as anticipated, but the expression levels of MT went up and the cells become much more sensitive to cancer drugs,” explained Ateeq.

Basically, targeting the SPINK1 gene for therapy is just like killing two birds with one stone.

In the study, published online in the Oncogenesis journal in August, the researchers demonstrated the heightened sensitivity to the drug doxorubicin in SPINK1-silenced colorectal cancer lines in the lab.

Ateeq said the team is now focusing on the mechanisms to target the SPINK1 gene.

The study has implications globally, she said, adding in India, there is a need to change mindsets.

“The molecular stratification of the cancer patients in India is very poor. There is a need to change mindsets and stress on what molecular drivers trigger CRC,” she added.

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