New research from ChristianaCare and the University of Delaware reexamines what we know about the early stages of colorectal cancer.
Dr. Bruce Boman, senior researcher at the Cawley Center for Translational Cancer Research at ChristianaCare’s Helen F. Graham Cancer Center and Research Institute, worked with a diverse team of specialists, including pathologists, tumor biologists, engineers, and mathematicians.
What they found changes earlier conceptions about colorectal cancer and how it starts.
“We have come up with the rules that regulate the normal tissue kinetics - we call it homeostasis - in the colon,” Boman explains. “And so we know what those rules are that regulate the healthy tissue throughout our adult life, and we have now figured out how those rules get disrupted.”
When those rules get broken, he says, colorectal cancer can occur.
While cancer is the result of cells dividing too rapidly, Boman’s research finds another step in the process - a slowing of cell growth that Boman characterizes as a bottleneck or a cellular traffic jam. The cause of the slowdown is a mutation in a gene called APC. Rather than speeding up cell growth, the APC mutation slows the renewal of cells in the colon. That mutation shows up in about 90% of colorectal cancer cases.
“Cells back up behind that traffic jam, and the backed up cells continue to divide,” he explains.
Understanding the bottleneck opens up new pathways to potential treatments. Boman thinks that a combination of two already-existing drugs may help clear up the traffic jam.
“It takes a two-pronged approach, we think, now to really effectively treat cancer. So that's where we're at right now in the laboratory,” Boman says.
But, he cautions, taking that theory to patients is not going to happen overnight. There are a number of necessary regulatory hoops to jump through. Still, Boman is optimistic.
“Our preclinical data is very strong,” he says. “So we're ready now to take the next step into the clinic.It's just we have to go through all the regulatory mechanisms to do that.”
Crucial to the research is the mathematical analysis, performed by a University of Delaware team led by Dr. Gilberto Schleiniger.
“Traditionally, mathematics is used to solve complex scientific problems,” Boman says. “Well, cancer is an extremely complex problem. We should be using mathematics to solve this complex problem of cancer.”
Colorectal cancer is one of the most lethal and prevalent forms of the disease. Globally, there are nearly 2 million diagnoses each year and some 930,000 deaths, according to the World Health Organization.
“Colorectal comes in third in terms of incidence, but it's a fairly lethal disease, so it's the second leading cause of cancer deaths,” he says.
Also troubling is the rise in colorectal cancer among younger adults in recent years. One in five diagnoses occurs in adults under the age of 55, according to the American Cancer Institute, and a study published in the Journal of the American Medical Association earlier this year shows that colorectal cancer deaths in people under 50 have surged since 2005, becoming the leading cause of cancer deaths in that age group.
“These younger people are not within the age group that we traditionally screen for,” Boman says. “So when they are diagnosed, it's quite often more advanced disease rather than catching it early when it's curable or even catching the pre-malignant polyps that we can remove to prevent the cancer.”
Colorectal cancer is treatable, Boman notes - if it’s caught early enough.
“It's curable if you catch it early, very curable, so that's why we very strongly recommend that they undergo screening,” Boman says.
He recommends that younger people try to find out if there is a history of cancer in their family and consider genetic analysis if there is.
