Genes Are Not The Only Drivers Of Colon Cancer

Genes are not the only drivers of colon cancer. A new study suggests cellular factors play an equally important part, and these not only drive tumor growth, but also affect how well the disease responds to chemotherapy.

Senior study author John Dick, of the Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, and colleagues, write about their findings in a paper published online in Science on Thursday.

Using lab-bred mice with poor immune systems to grow human colorectal cancers, they found biological factors and cell behavior, not just genes, drove tumor growth and contributed to treatment failure and relapse.

Dick, who is also a Professor in the Department of Molecular Genetics at the University of Toronto, says in a press statement that the study represents a "a major conceptual advance in understanding tumor growth and treatment response".

Not All Cancer Cells are Equal

For their study, Dick and colleagues found a way to follow single tumor cells as they developed with time.

They discovered that not all cancer cells are equal. Only some keep the cancer growing, and within this group, there are further differences: for instance some cells drove growth for long periods, up to 500 days, while others stopped after 100 days.

They also found a class of cancer-driving cells that lies dormant before being activated.

And they were surprised to discover that the mutated genes were the same for all the different cell behaviors.

Cells Responded Differently to Chemo

Dick and colleagues then tested the effect of chemotherapy on the human tumors growing in the immune-deficient mice.

They found that the treatment generally killed off the longer-term tumor-driving cells.

But unexpectedly, instead of killing the shorter-term tumor-driving cells, chemotherapy brought them out of their dormant state into an active state, causing tumors to grow again.

And again, the researchers found the tumor-driving cells that survived had the same mutations as the ones killed off by the treatment.

They say this proves it was cellular factors and not genetic mutation that was responsible for treatment failure.

"Paradigm Shift" Challenges Conventional View

The findings challenge the conventional view that tumor growth and chemotherapy resistance are governed purely by the genetic mutations in the cells of the tumor.

"The data show that gene sequencing of tumours to find the spectrum of their mutations is definitely not the whole story when it comes to determining which therapies will be most effective," says Dick.