Colorectal cancer cells may be coaxed to turn back into normal tissue simply by reactivating a single gene, scientists say.
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 4 days.
Tumours were eliminated within 2 weeks, and signs of cancer were prevented months later.
The findings provide proof of principle that restoring the function of a single tumour suppressor gene can cause tumour regression and suggest future avenues for developing effective cancer treatments, researchers said.
“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 of the Memorial Sloan Kettering Cancer Center in New York.
Up to 90 per cent 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 of Weill Cornell Medical College.
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.
Tumours regressed and disappeared or reintegrated into normal tissue within 2 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.