Heidi Ledford in Nature:
In cancer research, no success is more revered than the huge reduction in deaths from childhood leukaemia. From the 1960s to the 2000s, researchers boosted the number of children who survived acute lymphoblastic leukaemia from roughly 1 in 10 to around 9 in 10. hat is sometimes overlooked, however, is that these dramatic gains against the most common form of childhood cancer were made not through the invention of new drugs or technologies, but rather through a reassessment of the tools in hand: a dogged analysis of the relative gains from different medicines and careful strategizing over how best to apply them side by side as combination therapies.
That lesson has particular relevance in cancer research today. A new class of immunotherapies — which turn the body's immune system against cancerous cells — is elevating hopes about combination therapies again. The drugs, called checkpoint inhibitors, have already generated great excitement in medicine when applied on their own. Now there are scores of trials mixing these immune-boosting drugs with one another, with radiation, with chemotherapies, with cancer-fighting viruses, with cell treatments and more. “The field is exploding,” says Crystal Mackall, who leads the paediatric cancer immunotherapy programme at Stanford University in California. Fast-moving trends in cancer biology often fail to meet expectations, and little is yet known about how these drugs work together. Some observers warn that the combinations being tested are simply marriages of convenience — making use of readily available compounds or capitalizing on business alliances. “In many cases, we're moving forward without a rationale,” says Alfred Zippelius, an oncologist at the University of Basel in Switzerland. “I suspect we'll see some disappointment in the next few years with respect to immunotherapy.” But many clinicians argue that delay is not an option as their patients queue up for the next available clinical trial. “Right now I have more patients that could benefit from combinations than there are combinations being tested,” says Antoni Ribas, an oncologist at the University of California, Los Angeles. “We're always waiting on the next slot.”