“It may be tough to convince patients, even those with an incurable disease, that the best approach is not to kill as many cancer cells as possible but as few as necessary.” — James DeGregori and Robert Gatenby, Scientific American, August, 2019
When his wife, Nancy, was diagnosed with metastatic cancer, veteran science reporter George Johnson was determined to learn everything he could about the disease. She survived (and then, as he stoically recounts, left him) while he wrote the best non-specialist book, IMHO, on cancer: The Cancer Chronicles. His research convinced him that once the body had created cancerous cells, it was impossible to completely eliminate them through chemotherapy because “backed into a corner, they try to mutate their way out of trouble.”
Mutations are how cancer cells originate in the first place. With some 4 million cell divisions taking place in our bodies every second, it’s inevitable that some slightly-off copies will occur. And while most won’t survive, the odd ones will thrive and reproduce, out-competing regular, healthy cells. That’s cancer. Since cancer cells reproduce faster than most healthy ones, conventional treatment calls for knocking them out while they’re dividing and at their most vulnerable. Which is why chemotherapy, in addition to selectively hitting cancer cells, kills other fast-dividing body cells, including those in hair follicles (hence hair loss), stomach lining (nausea) and bone marrow (source of blood cells, including white cells, hence immunosuppression).
Johnson’s conclusion was prescient in the light of the Scientific American article published this month: “The best response might not be to fight back with chemotherapy and radiation, increasing the stress, but to somehow maintain the exuberant cells — the tumor — in a quiescent state, something that can be lived with.”
As DeGregori and Gatenby explain it, the idea of living with cancer cells, rather than quixotically trying to completely eliminate them from a patient, has its analogy in crop treatment. Many modern farmers drench their fields with pesticides such as pyrethrin compounds; more than 2 million tons of industrial pesticides are used globally every year.
Evolution tells us that in any population there will always be some pests that develop resistance and thrive once their “weaker” cousins are eliminated. The stronger the pesticide, the more resistant the survivors. So agricultural scientists have been recommending “integrated pest management,” the strategic use of pesticides to control but not eliminate crop-eating critters, thus maintaining the vulnerability of most pests to pesticides.
Same with chemotherapy. Instead of giving a patient with a cancerous tumor the maximum tolerated dose, or MTD (i.e. just short of killing them), give them just enough (typically 40 percent of the MTD) to contain the tumor. After treatment, the tumor will still have both chemo-sensitive cells and chemo-resistant cells, but the former will outnumber the latter, keeping the resistant cells in check (see graphic). Another course of chemotherapy will be required since the tumor (now reduced) is still there. But now it will be vulnerable to chemotherapy, whereas a recurring tumor following conventional treatment usually isn’t.
This evolution-based “adaptive therapy” is still in trial stages but shows promise in the treatment of a small group of patients with metastasized prostrate cancer: average survival 34+ months vs. 13 months with conventional chemo. It may not be the silver bullet oncologists once dreamt about, but by working with evolution in this way, physicians may be able to help cancer patients live with their disease into old age.
Barry Evans (barryevans9@yahoo.com) has to remind himself that cancer is an inevitable consequence of evolution and that dinosaurs died from it, too.
This article appears in Light into Dark Places.
“Prostrate” cancer seems an appropriate descriptor in the context 🙂
Prostate! Damn! That gets me every time! Thanks Pat. Prostate. Prostate. Prostate.
Meanwhile, Dr. DeGregori commented on my article, noting (where I said Mutations, after all, are how cancer cells originate in the first place):
“While cancer development requires mutations, we have been arguing that the tissue context that determines whether or not cancer-causing mutations provide cells with an advantage is key. For example, 90% of cancers occur in individuals over 50. While older ages do allow for more mutations to accumulate, studies by my lab and others have shown that the same cancer-causing mutations that are not selected for in young tissues are potently selected for in aged tissues.
Also, re my writing that cancer cells reproduce faster than healthy ones:
“some cancers show very slow doubling rates. The main feature of cancers that makes them dangerous is that they disobey the rules they dont differentiate when they are supposed to, they divide when theyre not supposed to, and they dont obey boundaries (thus invading other tissues).”
This is why radiation therapy is often given in “fractions” over 10 to 44 treatments over 2 to 8.5 weeks, depending on the tumor type. If the full dose was given at once, that could be lethal, but the cumulative dose given over a longer period is what ultimately results in tumor death (not patient death). With fractionated treatment the goal is not to kill the cancer with the first treatment, but rather using the entire course for “tumoricide.” If a patient is getting surgery after treatment, a lower dose of radiation (and chemo) is given with the understanding that there will be residual tumor at the time of surgery.