Gene that can reverse cancer effect found


New York, June 21 (IANS): In a major development of cancer treatment, now the cancer cells can be turned back into normal tissue simply by reactivating a single gene, new reserach says.

Anti-cancer strategies generally involve killing off tumour cells. Now, researchers found that restoring normal levels of a human colorectal cancer gene in mice stopped tumour growth and re-established normal intestinal function within only four days.

Remarkably, tumours were eliminated within two weeks, and signs of cancer were prevented months later. The findings suggest future avenues for developing effective cancer treatments.

Colorectal cancer is the second leading cause of cancer-related death in developed countries, accounting for nearly 700,000 deaths worldwide each year.

"Treatment regimes for advanced colorectal cancer involve combination chemotherapies that are toxic and largely ineffective, yet have remained the backbone of therapy over the last decade," said senior study author Scott Lowe from Memorial Sloan Kettering Cancer Centre, New York.

Up to 90 percent of colorectal tumours contain inactivating mutations in a tumour suppressor gene called adenomatous polyposis coli (Apc).

Although these mutations are thought to initiate colorectal cancer, it has not been clear whether Apc inactivation also plays a role in tumour growth and survival once cancer has already developed.

"We wanted to know whether correcting the disruption of Apc in established cancers would be enough to stop tumour growth and induce regression," said first author Lukas Dow from Weill Cornell Medical College.

This question has been challenging to address experimentally because attempts to restore function to lost or mutated genes in cancer cells often trigger excess gene activity, causing other problems in normal cells.

To overcome this challenge, Lowe and his team used a genetic technique to precisely and reversibly disrupt Apc activity in a novel mouse model of colorectal cancer.

While the vast majority of existing animal models of colorectal cancer develop tumours primarily in the small intestine, the new animal model also developed tumours in the colon, similar to patients.

Consistent with previous findings, Apc suppression in the animals activated the Wnt signalling pathway, which is known to control cell proliferation, migration, and survival.

When Apc was reactivated, Wnt signalling returned to normal levels, tumour cells stopped proliferating, and intestinal cells recovered normal function.

Tumors regressed and disappeared or reintegrated into normal tissue within two weeks, and there were no signs of cancer relapse over a 6-month follow-up period.

Moreover, this approach was effective in treating mice with malignant colorectal cancer tumours containing Kras and p53 mutations, which are found in about half of colorectal tumours in humans.

"It is currently impractical to directly restore Apc function in patients with colorectal cancer, and past evidence suggests that completely blocking Wnt signalling would likely be severely toxic to normal intestinal cells," Lowe said.

"However, our findings suggest that small molecules aimed at modulating, but not blocking, the Wnt pathway might achieve similar effects to Apc reactivation," he added.

The study was published in the journal Cell.

  

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Title: Gene that can reverse cancer effect found



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