When the researchers targeted glutamine metabolism or nucleotide production for even just one day, resistant cells were eliminated and disease survival improved.

“This opens a whole new set of possibilities for targeting these cells because you’re no longer just looking for drugs that can target genetic mutations, which is difficult to do,” van Gastel said. “Metabolic programs are driven by enzymes, and from a chemical point of view they are much easier to target pharmacologically using small molecules and drugs.”

Currently, several companies are developing potential drugs that inhibit this metabolic pathway, although not necessarily intended for cancer treatment. The researchers hope that an inhibitor can be repurposed and combined with chemotherapy to improve patient outcomes.

“If you give the inhibitor to patients who have undergone chemotherapy, you might not need to give them this new drug for a very long period. You can really target that exact moment of metabolic change, which might avoid some of the toxicity issues associated with longer term treatments,” van Gastel said.

Beyond leukemia, the researchers believe their approach has broader applicability. Scadden said: “In other types of cancer and diseases, the cells’ environment contributes to and often drives the outcome. Viewing these problems in the context of dynamic ecosystems can often lead to new approaches, but it does require moving away from the reductionist view of single genes or single cells. Find a key moment or pathway in the lives of cell communities, and we might be able to make a difference. It’s a bit like the keystone in an arch: studying that one stone won’t tell you much, but consider it in terms of the time of its placement and the stones beside it, and you really see its meaning.”

This study was supported by Alex’s Lemonade Stand Foundation, Tap Cancer Out, the Koch Institute – DF/HCC Bridge Project, the Swedish Research Council, the National Institutes of Health, the MIT Center for Precision Cancer Medicine, the Ludwig Center at MIT, the Howard Hughes Medical Institute, the Harvard Stem Cell Institute, the Ludwig Center at Harvard, and the Gerald and Darlene Jordan Chair of Medicine at Harvard.