As tools for detecting cancer early have improved, medical understanding simply has not kept up. Finding tumors early is of limited help when doctors still struggle to tell which cancers are highly aggressive and likely to spread and which are slow-growing and benign, leading to a long-running debate over the benefits and possible harm of screening.
A new study may offer a valuable clue about how cancers become aggressive, identifying a genetic switch that in some breast cancer cells is poised to be flipped by signals from the surrounding tumor environment.
When the switch is triggered, it helps transform nonaggressive cells into cancer stem cells capable of proliferating and spreading. The genetic switch, researchers found, is positioned differently in two types of breast cancer that have very different prognoses.
“The fact of the matter is, when it becomes a cancer stem cell, it acquires tumor-initiating ability, capable of spawning an entire new tumor,” said Robert Weinberg, a founding member of the Whitehead Institute for Biomedical Research in Cambridge who led the research. “It could be that we’ve stumbled on what may be the root cause between the two different kinds of cancer.”
Weinberg cautioned that the work, published this month in the journal Cell, was basic science and it is far too soon to know its relevance to understanding human disease. But it may help explain how cancers in the same organ can take such different paths.
Weinberg and colleagues discovered that whether tumor cells responded to signals sent by the surrounding microenvironment depended on the status of a gene called ZEB1.
A subtype of breast cancer called luminal cancers, which generally have a far better prognosis, have the ZEB1 gene “locked down,” Weinberg said. That means even when those cancers are exposed to environmental triggers, ZEB1 doesn’t get activated.
In basal breast cancers, which tend to be aggressive — with about a quarter of patients dying within five years of their diagnosis — that gene is primed and ready to spring into action with the right triggers.
“This may be getting us very close to the root cause of the profound difference between the two different kinds of cancer,” Weinberg said.
Weinberg said he hoped to examine human breast cancer tissue samples next, to see whether the status of the gene was predictive of how aggressive patients’ cancers were.
Weinberg also plans to examine whether the same activating mechanism could account for the difference in virulence of other cancers in which oncologists struggle to distinguish those that are benign from those that will spread throughout the body.Carolyn Y. Johnson can be reached at firstname.lastname@example.org. Follow her on Twitter @carolynyjohnson.