
Cancer is a disease, or group of diseases, in which some cells proliferate uncontrollably and can spread to other parts of the body. But that description doesn’t reflect how our conception of cancer has changed, says at Johns Hopkins University in Maryland. “People used to view cancer as sort of bad luck: the cancer would just change over time and we didn’t really understand why, or how, or what was driving those changes.”
In the past few years, however, Pienta and others have come to see cancers as akin to organisms themselves, existing in complex ecosystems alongside other cancer cells and host immune cells. Cancer cells compete for access to nutrients, and only the fittest survive. “Cancer evolves in response to changes in its environment,” says Pienta. “If it didn’t, it would die.”
Ultimately, this is the reason why cancer kills so many people. Cancer cells divide rapidly, so random mutations occur often and any that confer an advantage are quickly selected for. “They’re evolving to become the best cancer cell they can become and that typically is bad news for the patient,” says co-director of the Cancer Biology and Evolution Program at the Moffitt Cancer Center in Florida.
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What’s more, the hardiest cells are better at getting into the bloodstream and spreading to other parts of the body, a process known as metastasis. “We have got good drugs and initial therapies for most types of cancers,” says Gatenby. “But in the metastatic setting, you’re almost never cured.”
The good news is that viewing cancer through an evolutionary lens suggests new ways to treat it, says Gatenby. Among them is the idea that, rather than trying to wipe out cancer cells, we should manage the disease almost as if it were a chronic condition like diabetes.
Adaptive cancer therapies
Conventional treatments like chemotherapy or radiotherapy will always leave behind a small population of resistant cells. With their competition wiped out, they quickly proliferate – and the cancer becomes much harder to treat. However, Gatenby’s lab is experimenting with ways to keep some treatment-responsive cells alive so that they compete with the resistant cells.
“We only give a little bit of the treatment and then stop,” says Gatenby. “The tumour will come back, but because you’re not applying any selection for resistance, the sensitive cells will dominate.”
Another strategy could be to target cancer’s ability to adapt. Pienta’s team has discovered that when people are given chemotherapy, a tiny subset of cancer cells stops dividing and enters a state of hibernation. These can hide from chemo drugs. Pienta believes that by destroying them, we could collapse the whole cancer ecosystem.
It may even be possible to stop cancers before they have a chance to evolve. at the Francis Crick Institute in London has found that when people experience chronic inflammation as a result of exposure to air pollution or tobacco smoke or alcohol, immune cells can kick-start cancer development.
This opens yet another avenue of treatment: target the immune cells that cause cancers to grow in the first place. “The normal ecosystem is not subjected to the sort of genome instability that cancers are, so the targets are much more stable and potentially more tractable,” says Swanton.
Ultimately, scientists believe that their new conception of cancer may allow us to cure it. “Our big advantage is that cancer cells can only adapt to the here and now,” says Gatenby. “They can never anticipate the future. But humans can.”