The results of a small study could lead to better identification of polyps that are likely to develop into invasive colorectal cancer.

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Researchers investigate cancer’s ‘founding cells.’

This may prevent the unnecessary treatment of patients with harmless growths, say scientists from Duke University in Durham, NC, and the University of Southern California (USC) in Los Angeles, who report their results in the journal PNAS.

There are around 1.3 million people living with colorectal cancer in the United States, where around 4 percent of people will develop the disease during their lifetime.

The cancer usually starts as a small growth or polyp in the lining of the colon or rectum. Screening methods that look for and remove these growths from the gut can prevent cancer.

“Thanks to improved screening technologies,” explains senior study author Darryl Shibata, who is a professor of pathology at USC’s Keck School of Medicine, “we diagnose more and more small tumors.”

There is a drawback, however, in that better screening “also leads to overdiagnosis” — especially as currently there is no certain way to differentiate between benign and malignant tumors at such an early stage.

So, using mathematical models and genome sequencing, the researchers decided to look for cell features that might drive polyps toward malignancy.

Their search revealed that malignant — but not benign — tumors have a genetic signature of “cell movement” capability, even at the early stage of growth.

This is significant, as cells that express these features are capable of “invasion and metastasis,” which is the leading cause of death in cancer.

Metastatic cells “penetrate the surrounding tissues,” then travel through the lymph system or the bloodstream and set up secondary tumors in other parts of the body.

“By testing screen-detected, small tumors,” says first study author Dr. Marc D. Ryser, who is a researcher in the Departments of Surgery and Mathematics at Duke University, “for early cell movement as a sign of malignancy, it might be possible to identify which patients are likely to benefit from aggressive treatment.”

The study follows earlier work that showed that the final tumors of some cancers carry genetic signatures that are already detectable in the “founding cell.”

This led the researchers to wonder whether growths that become invasive tumors “are born bad” — that is, the traits that give them this ability are there from the beginning and not acquired as they grow.

In the new study, Prof. Shibata and his colleagues analyzed “19 human colorectal tumors.” They found genetic signatures of “early abnormal cell movement” in 9 of the 15 tumors that were malignant and in none of the four that were benign.

“The early growth of the final tumor,” note the authors, “largely depends on the drivers present in the founding cell.”

Although the findings suggest that it might be possible to distinguish between deadly and harmless growths in their very early stages, the authors caution that their study was only small, and there is now a need to replicate the findings with much larger samples.

“Because treating a patient aggressively can cause them harm and side effects, it is important to understand which of the small screen-detected tumors are relatively benign and slowly growing, and which ones are born to be bad.”

Prof. Darryl Shibata