A Message from Dinosaurs
The standard approach to treating these tumors is to use a powerful, broadly active form of chemotherapy after surgery. And this is especially true for rhabdomyosarcoma, which, because of its potentially lethal recurrence, is usually treated with extremely powerful chemotherapy. Dr. Isakoff and his colleagues liken this approach to the prehistoric asteroid that hit the earth and so radically changed the environment that the dinosaurs could not survive. This titanic event wiped out most of the species on earth. But our small, rat-like mammal ancestors had adaptations that let them survive on the dark, cold planet where others couldn’t. In the absence of any competition, this once-marginal creature thrived, and we mammals flourished. The same thing happens in a tumor when it is hit by a heavy blast of chemotherapy.
That is, the blast destroys most of the various cell types in the tumor, especially the most numerous, dominant forms. But it doesn’t kill all of the cells. Somewhere in the tumor there will be a few cells of a certain type that are resistant to the chemotherapy. And in the absence of competition from other cancer cells, the survivors thrive. This is why relapsed rhabdomyosarcoma is so dangerous—it is made primarily of cells that are resistant to the strongest drugs we can safely use on children. And that safety issue is important: it gives a further advantage to those rogue cancer cells, since they don’t have to be completely invulnerable; they only have to be slightly more resistant than a child’s healthy cells.
Why Tumors are Like Pigeons
So what to do? Here, Dr. Isakoff and his colleagues look to the example of the passenger pigeon. At one time, these birds were among the most numerous species on earth, with a population of perhaps four billion. And they were particularly numerous in the United States. A large flock would darken the sky with its numbers and might take hours to completely pass overhead. Now, they are extinct. The passenger pigeons’ demise did not come from a single catastrophic event, like an asteroid. Instead, it was because several apparently unrelated circumstances worked together to make survival impossible.
Large tracts of forest the birds needed for nesting were cut down as the country was settled. That made them vulnerable to predators and took away food sources. When they turned to farmer fields for food, people shot them in such large numbers that their population collapsed and extinction followed. This kind of process, called background extinction, can inform the way we treat rhabdomyosarcoma.
The goal is to undermine the background conditions that allow resistant cancer cells to survive—the equivalent of cutting down their forests. That means finding a different kind of secondary treatment to follow the initial chemotherapy blast. That is part of Dr. Isakoff’s research collaboration.
The final part of this evolutionary approach to sarcoma treatment deals with what we do while we’re waiting for that cure. And here the researchers looked to agriculture.
Bugs to the Rescue
For decades, farmers used powerful pesticides to kill insects that ate their crops. And those chemicals appeared to work. Insects were all but wiped out. But, just like the asteroid situation and cancer tumors, there were a handful of insects whose genes made them able to survive the pesticides. And because the pesticides had destroyed all their competitors, the survivors thrived. Their populations boomed, and the pesticides that had cleared the way for them were now powerless to stop them.
So farmers started using lower amounts of pesticides, enough to reduce the overall pest population while still maintaining the genetic diversity of that population. That way, pesticide resistant strains couldn’t get a foothold. The bugs still ate crops, but at a sustainable level.
Dr. Isakoff and his colleagues have proposed a similar approach with rhabdomyosarcoma. If initial treatment involves lower doses of chemotherapy, it ought to slow the growth of the tumor while maintaining the genetic diversity of its cells and prevent resistant strains from taking over. Those lower doses could be repeated periodically as the tumor recovers from the first dose. As with the farmer, it is not ideal: the child still has cancer. But it could extend the amount of time the child can live with that cancer and perhaps buy some time for the research to find a more permanent treatment. And it means the child does not suffer the extreme side effects of extreme chemotherapy.
It’s a radical idea, but it holds tremendous promise, and it is being applied in clinical trials now. Seventeen hospitals, including Connecticut Children’s, are recruiting patients to participate. Ninety-six percent of federal cancer research dollars go to adult cancers, leaving a mere four percent for pediatric cancer. That means that philanthropy like yours is absolutely critical for discovering new approaches. You make this work possible.