Stopping Cancer Before It Starts: The Promise of the Pre-cancer Genome Atlas

Issue 28, Winter/Spring 2016


Imagine, in the not-too-distant future, a routine visit to your doctor’s office. As usual, samples of blood or urine are taken for testing. Then, a bit later, you get the news: Special “biomarkers” in those samples suggest you are at especially high risk of developing a specific type of cancer.

Appropriate preventive methods are then ordered – lifestyle change, chemopreventive drugs, other interventions. And the cancer – which could have threatened your life – has been stopped before it began.

Sound like science fiction? It could soon be science fact, once a bold, collaborative project dubbed the Pre-cancer Genome Atlas gets underway. 

Dr. Avi Spira directs the BU-BMC Cancer Center at Boston University and is a leading light behind the project.  He envisages a global collaboration of scientists combing through millions of “data points” focused on processes that push healthy cells to become cancerous ones.

“The idea behind the Pre-cancer Genome Atlas is to identify those genomic, cellular and molecular changes that characterize pre-cancer as an evolving cancer,” he explained. “Because if we intercept the disease earlier in the process – in the pre-disease state – we’ll have much more success in preventing disease from happening, maybe even reverse the disease process once it’s begun.”

This would represent a paradigm shift in cancer care, Spira believes.

“We want to eradicate cancer, that’s the goal here: Eradicate it, because it never happened.”

Key advances

According to Spira, recent innovations in medical research technology have paved the way for a project such as the Atlas.

“First are the advances in next-generation gene-sequencing technology,” he said.

In years past, cataloguing the intricacies of DNA and RNA molecules – the cell’s “blueprint” components – was an arduous, expensive process. However, in the past decade, there’s been an explosion in less costly and rapid sequencing technologies that are now in common use at most major research centers.  

Alongside that has come a revolution in computational science, “that’s allowed us to make sense of the data and identify genomic changes that characterize pre-malignant states,” Spira said.

There have also been new insights at the molecular level into how the body’s immune system either fights off cancer – or is compromised and weakened.

That’s important, Spira explained, because every human being’s immune system is naturally fighting off “pre-cancers” all the time.

“The real challenge is that we don’t know which of these pre-cancers is going to go on to become a full-blown lethal cancer,” he said. “If we could find those that are and intercept them early, we’d be much more effective in preventing the disease.”

Early examples

The first of these “premalignancy” tests are, in fact, already here. For example, Cologuard, which looks for genomic “biomarkers” of either pre-cancerous or cancerous colon lesions in stool, was approved by the U.S. Food and Drug Administration in 2014.

Cologuard’s effectiveness relies on spotting “some of the mutations in genes that characterize an early colorectal cancer,” Spira explained.

People who test positive from the screen are recommended to undergo colonoscopy.

Spira, a lung cancer specialist, also pointed to a test he helped develop called Percepta. The test analyzes key genomic alterations in bronchial airway cells to gauge a patient’s risk for the number one cancer killer.

Tests focused on mutations in BRCA genes – long tied to breast and ovarian cancers – are also examples of “premalignancy” screens that help guide decisions on cancer prevention.

“Now we have modalities available for screening colorectal, lung, breast and several other malignancies, and that’s allowed us to potentially identify the pre-malignant lesions before they become cancer,” Spira said. “But we still struggle to identify which of these precancerous lesions is destined to become an invasive and lethal cancer”

The Road Ahead

A handful of tests is a good beginning of course. But high-powered data mining – conducted in a collaborative, multi-disciplinary way – could usher in many new insights into premalignancy.

The Pre-cancer Genome Atlas represents just that sort of concerted approach to this new field, Spira said.

“The idea is to create a sort of ‘Manhattan Project,’ if you will – a biomedical research community consortium where we collect these premalignant samples when we can and study them thoroughly, comprehensively, with the latest and greatest molecular tools,” he explained.

“Through our computational biology, we may then understand the sequence of events that lead to cancer and – potentially – have a better way of identifying who is truly incubating a cancer that’s likely to kill them,” Spira said.

How long would it take to complete the Pre-cancer Genome Atlas? Once it got up and running, perhaps 5 to 10 years, but it is difficult to predict, Spira said.

An article outlining the promise of the approach, published early in 2016 in the journal Cancer Prevention Research, has already generated great interest.  “That paper was a call to arms,” Spira said.

“Will it ever get to that ‘Manhattan Project’ that I am envisaging?” Spira said. “I hope so – we’re not there yet, but that would be the goal.”

The final goal is routinely stopping cancer before it starts.

“An ounce of prevention is worth a pound of cure,” he said. “If you can get in early, you can have a much bigger impact on the disease process.”

Avrum Spria, MD, MSc

Avrum Spria, MD, MSc
Chief, Division of Computational Biomedicine, Boston University School of Medicine
Director, Translational Bioinformatics Program, Clinical and Translational Science Institute
Professor of Medicine, Pathology & Laboratory Medicine, and Bioinformatics