Genomic studies track early hints of cancer

Pilot projects aim to pinpoint how benign tumours turn into lung, breast, prostate and pancreatic cancers.

Researchers are trying to stop tumour cells from turning malignant like this pancreatic cancer cell.

After years of studying advanced cancers, researchers are now training their DNA sequencers on precancerous growths to learn more about how they develop into the full-blown disease.

A three-year pilot project funded this month by the US National Cancer Institute (NCI) as part of the National Cancer Moonshot Initiative, will take this approach with lung, breast, prostate and pancreatic cancer. Investigators hope to create a ‘pre-cancer genome atlas’ by sequencing DNA from precancerous growths, in addition to sequencing RNA from individual tumour cells and identifying the immune cells that have infiltrated the lesions.

Another project — a four-year US$5-million effort funded by the charities Stand Up To Cancer, the American Lung Association and LUNGevity announced on 26 October — will bolster the study in lung cancer by sequencing DNA from precancerous growths in the airway. Doctors sometimes monitor such lesions, taking periodic biopsies to determine if and when they become malignant. One component of this project will track the genetic changes in these biopsies over time.

The aim is to find ways to intervene in cancer earlier, when it may be easier to rein in the disease. “There’s a tremendous sense that the rate-limiting step for new approaches for either preventing cancers or detecting them early, is the fundamental lack of knowledge about the earliest molecular events,” says pulmonologist Avrum Spira at Boston University in Massachusetts, a leader on both projects. “We just don’t understand what’s going on very early.”

Making maps

The desire to map those earliest events has been growing, fuelled in part by frustration with the limited success of therapies in patients with advanced cancers. Meanwhile, technological advances in DNA sequencing have made it possible for researchers to glean useful data from tiny tissue samples — a crucial development because physicians tend to take small biopsies of precancerous growths, and there is often little tissue left after the pathologists have analysed them.

However, even with advances in sequencing, sceptics have questioned whether those minuscule amounts of tissue would suffice, says Spira. The Moonshot-funded project is set to last for three years, but Spira and his colleagues have been asked to report back in 12 months so that the NCI can decide whether the approach is feasible and warrants expansion, Spira says. “This is the beginning of a much bigger initiative,” he says.

It’s a short timeline, but the team has a head start, Spira says. Several institutions have already been collecting these small tissue samples in biobanks, so investigators can begin their analyses immediately. This will be particularly important for pancreatic cancer, a relatively rare condition that is often caught only when it has become advanced and difficult to treat, he says.

But it is worth the extra effort to study pancreatic cancer, which is among the most lethal ones, says Elizabeth Jaffee, who studies the disease at Johns Hopkins University in Baltimore, Maryland. Many pancreatic tumours seem to be driven by mutations in the same genes — and that commonality may make the disease more predictable, and therefore easier to detect and target at an early stage.

“You can look at it as, ‘Let’s pick the easiest ones’, but will that have the biggest impact?” Jaffee says. “Or let’s pick some of the harder ones and maybe we can, longer term, have this plan of just preventing them entirely.”

If successful, the projects could herald a change in how researchers approach cancer prevention, says Spira. “The field has been stagnant and people are frustrated,” he says. “People want to really transform that space, and the feeling is that the atlas is the next thing to do to change that.”

Ref: Nature 551, 18 (doi:10.1038/nature.2017.22911