A Clever New Strategy for Treating Cancer, Thanks to Darwin

Most advanced-stage cancers mutate, resisting 
drugs meant to kill them. Now doctors are 
harnessing the principles of evolution to thwart that lethal adaptation.

by Roxanne Khamsi

In October 1854, a government entomologist was 
inspecting some farmland outside the town of 
Ottawa, in northern Illinois, when he came upon a 
disturbing scene in a cabbage patch.

The large outer leaves of the vegetables were 
“literally riddled with holes, more than half 
their substance being eaten away.” With each step 
he took around the ravaged cabbages, tiny swarms 
of little ash-gray moths rose from the ground and 
flitted away. This was, it appears, the first 
record in the United States of the 
moth, an invasive pest that in its larval form 
shows a fondness for cruciferous vegetables. By 
the late 1800s the moths were chewing through the 
leaves of cabbages, brussels sprouts, collards, 
and kale from Florida to Colorado.

To fight this invasion, farmers started 
bombarding their fields with primitive 
This worked. Or seemed to. It killed most of the 
moths, but those that survived the poison 
reproduced, and the population bounced back 
stronger than ever. For decades, one pesticide 
after another failed as the moths evolved to 
withstand it. Even the grievously toxic DDT was 
no match for the diamondback. Beginning in the 
late 1950s, agriculture experts started to 
abandon the idea of eradication and adopted a new 
strategy. Farmers would leave the moths alone 
until their numbers exceeded a certain threshold, 
and only then would they deploy pesticides. 
Remarkably, this helped. The moths did not die 
out, but the pest could be managed and crop damage held in check.

Gatenby heard this history of the diamond­back 
moth in 2008, he immediately latched onto it. 
Gatenby is not a farmer nor an agronomist nor a 
fan of cruciferous vegetables­in fact, he deeply 
loathes brussels sprouts. He is a radiologist by 
training and heads the radiology department at 
the H. Lee Moffitt Cancer Center in Tampa, 
Florida. But unlike your typical doctor, he is 
also obsessed with the evolutionary principles 
put forth more than 150 years ago by 
Darwin. The story of the diamondback moth 
appealed to Gatenby as a useful metaphor for his 
own project­one concerned not with crops but with 

Like the diamondback moth, cancer cells develop 
resistance to the powerful chemicals deployed to 
destroy them. Even if cancer therapies kill most 
of the cells they target, a small subset can 
survive, largely thanks to genetic changes that 
render them resistant. In advanced-stage cancer, 
it’s generally a matter of when, not if, the 
pugnacious surviving cells will become an 
unstoppable force. Gatenby thought this deadly 
outcome might be prevented. His idea was to 
expose a tumor to medication intermittently, 
rather than in a constant assault, thereby 
reducing the pressure on its cells to evolve resistance.

Just as ecologists allow for a manageable 
population of diamondback moths to exist, 
Gatenby’s method would permit cancer to remain in 
the body as long as it doesn’t spread further. To 
test this idea, Gatenby got permission in 2014 to 
run a trial on advanced-stage prostate cancer 
patients at Moffitt. The patients had cancer that 
no longer responded to treatment; their 
drug-resistant cells were winning an evolutionary 
battle within the body, surviving an onslaught of 
toxic <>drugs 
where weaker cancerous cells had succumbed. The 
hope was that, by using a precise drug-dosing 
scheme developed using evolutionary principles, 
they could slow the rise of the mutations that 
would endow some cancer cells with the fitness to 
survive. Gatenby's name for the approach was adaptive therapy.

One of the patients in the trial was Robert 
Butler, a British oil-exploration engineer who 
had retired in Tampa. In 2007 he was diagnosed 
with prostate cancer, and seven years later, 
after taking the drug Lupron and getting blasts 
of radiation, his prostate tumor had progressed 
to stage 4, advanced cancer. Butler did not give 
up, though. He tried a newly approved 
immunotherapy treatment­one that involved having 
cells from his blood sent by courier to a 
facility outside Atlanta, where they were mixed 
with a molecule that activates immune cells, and 
then shipped back to Florida to be injected back 
into him. The treatment was expensive­its sticker 
price can be as high as $120,000­but the threat 
that the cancer would progress remained.

When Butler and his wife showed up at his 
oncologist’s office at the Moffitt Cancer Center 
in August 2014, they braced for what would come 
next; they had heard about invasive treatments, 
like radioactive seed implants. So they were 
intrigued when the doctor told them about 
Gatenby’s trial and asked if Butler wanted to 
participate. He would take a powerful and 
exceedingly expensive drug called Zytiga, but not 
in the scorched-earth, kill-all-the-cells fashion 
that is standard. Instead he would receive only 
as much Zytiga as was necessary to stop the 
cancer from growing. The idea was radical and 
counterintuitive. His last best shot at escaping 
death from his cancer was to give up on curing it.

Knowing the modified Zytiga regimen wasn’t 
designed to rid him of cancer left Butler, the 
engineer, with a question about how the doctors 
would measure the success of their new treatment 
approach. He asked, “How do we know this stuff is 
working?” And one of his doctors replied, “Well, you won’t be dead.”

In the United States we use military metaphors 
when we talk about cancer. We battle and we 
fight, and if we survive, we’re victorious. The 
attitude traces back in part to 1969, when the 
Citizens Committee for the Conquest of Cancer ran 
an ad in The Washington Post and The New York 
Times imploring the president with the words “Mr. 
Nixon: You can cure cancer.” The call to action 
helped trigger the country’s “war on cancer” with 
a determination that, using enough medical 
weaponry, the malignant foe could be obliterated.

By the mid-1970s, however, signs were beginning 
to emerge that certain strategies aimed at total 
eradication were liable to backfire. Against this 
backdrop, a cancer researcher named Peter Nowell 
published a seminal paper in Science in 1976. 
Nowell conjectured that evolutionary forces drive 
certain cell populations in tumors to become 
progressively more malignant over time. The cells 
inside a tumor are in competition, not only with 
nearby healthy cells, Nowell argued, but also 
with each other. Nowell suggested­and later 
research confirmed­that certain 
<>DNA alterations 
grant cancer cells resistance against 
chemotherapy or other treatments, causing them to 
edge out drug-­sensitive cells through a process of natural selection.

Nowell conveyed his ideas to his students at the 
University of Pennsylvania School of Medicine, 
sometimes smoking a cigarette as he lectured. His 
theories were respected but slow to catch on. He 
emphasized that tumors may become deadlier as 
they accumulate more genetic errors. It was an 
idea ahead of its time. Scientists back then 
didn’t have the technical capability to measure 
all the changes in the vast genomes of tumor 
cells. Instead, they could sequence only little 
tidbits of DNA at a time, and most scientists 
viewed cancers as the fruit of just a few genetic mutations.

One of the medical students listening to Nowell 
lecture in the late 1970s happened to be a young 
Bob Gatenby. But Nowell’s ideas didn’t make a 
strong impression on him, Gatenby says; instead, 
what inspired him was what he witnessed in his 
first years as a practicing radiologist on the 
bloody front lines of the war on cancer.

“I couldn’t understand why you would treat 
someone with a fatal disease and kill them with 
your therapy. It just didn’t feel right to me.”

By the mid-1980s, Gatenby had secured a job at 
the Fox Chase Cancer Center in Philadelphia. At 
that hospital and others around the country, 
clinical trials were putting breast cancer 
patients through an extreme treatment: a 
combination of a potentially lethal dose of 
chemotherapy followed by a bone marrow 
transplant. The treatment was harrowing. The 
women had diarrhea and nausea, and some had so 
much lung damage they had difficulty breathing. 
Others experienced liver damage and weakened 
immune systems that left them vulnerable to 
serious infections. As a radiologist, Gatenby’s 
job was to interpret x-rays and other scans of 
the patients, and he saw the treatment failing. 
Out of more than 30,000 women with breast cancer 
in the US who underwent the procedure between 
1985 and 1998, as many as 15 percent died from 
the treatment itself. “What happened was these 
women suffered horribly, and they weren’t cured,” Gatenby says.

Around the same time as the breast cancer trials, 
the father of a colleague of Gatenby’s came to 
the hospital to receive an initial, aggressive 
round of chemotherapy for lung cancer. According 
to the colleague, her father arrived on a Friday 
with no apparent symptoms and was dead by Monday. 
“That event to me was very traumatizing,” Gatenby 
recalls, and the cause to him seemed obvious. “I 
couldn’t understand why you would treat someone 
with a fatal disease and kill them with your 
therapy. It just didn’t feel right to me.” During 
this fraught period, Gatenby’s own father died from esophageal cancer.

Gatenby felt there must be a better way to treat 
cancer­to outsmart it rather than carpet-bomb it. 
He had studied physics in college and believed 
that biologists could leverage equations to 
capture the forces driving cancer the same way 
physicists use math to describe phenomena like 
gravity. Whereas Nowell had put forth general 
theories about how cancers followed evolutionary 
principles, Gatenby was taking a further leap: He 
wanted to figure out a way to describe the 
evolution of cancers with mathematical formulas.

Robert Gatenby, a radiologist, saw patients 
suffer from intensive breast cancer treatments. 
He felt there must be a better way to treat 
cancer, to outsmart it rather than carpet-bomb it.

By 1989, Bob Gatenby was preoccupied with 
modeling the evolution of cancers. During the day 
he would scrutinize the x-rays of cancer 
patients, and at night, after he and his wife had 
put their young kids to bed, he would sit at the 
kitchen table in their suburban Philadelphia home 
and pore over medical journals. The patterns he 
started seeing in the literature led him to a 
question: What if cancer cells outcompete normal, 
healthy cells in the body in the same way an 
animal species edges out its competitors in nature?

Gatenby recalled that ecologists had come up with 
equations to describe the balance between 
predators and prey. As an undergraduate at 
Princeton University, he had learned the classic 
example of the math that plotted how growing 
populations of snowshoe hares fuel the rise of 
the lynx that feed on them. He began dusting off 
old books and buying new ones to educate himself on species interactions.

For a year Gatenby read and mulled. Then, in 
1990, on a family trip to the Atlantic coast of 
Georgia, he found himself stuck in a hotel room 
one afternoon with his two napping children. Out 
of nowhere, an idea presented itself. He grabbed 
a pad of hotel stationery and a pen and began 
scribbling down some key formulas from population 
ecology. Those formulas, called Lotka-Volterra 
equations, have been used since the 1920s to 
model predator-prey interactions and, later, 
competition dynamics between species, and were 
among the ones he had recently brushed up on at 
home. Gatenby thought this set of formulas could 
also describe how tumor cells compete with 
healthy cells for energy resources such as the glucose that fuels them.

When he returned to Philadelphia, he spent what 
time he could at a typewriter composing a paper 
that laid out this theoretical model. As soon as 
he finished, he showed it to some colleagues. He 
didn’t get the response he had hoped for: They 
thought it was ridiculous to try to use 
ecological equations to model cancer. “To say 
that they hated it would not do justice to how 
negative they were about it,” he says. His peers 
thought that a brief set of formulas couldn’t 
capture cancer’s seemingly infinite complexities.

Louis Weiner, who worked alongside Gatenby at the 
time, recalls that their colleagues viewed 
Gatenby’s ideas as offbeat. “Treatment orthodoxy 
at that time favored high-intensity, dose-dense 
treatments aiming to eradicate every last tumor 
cell in a cancer patient,” says Weiner, who is 
now director of the Georgetown Lombardi 
Comprehensive Cancer Center in Washington, DC. 
“Bob’s perspective was antithetical to those beliefs.”

But Gatenby pressed on and succeeded in getting 
the paper, chock-full of Lotka-Volterra 
equations, accepted in the prominent journal Cancer Research in 1991.

Despite the publication of his theory, he still 
couldn’t convince oncologists that his idea had 
practical merit. “I think that they felt 
intimidated,” Gatenby says. “Most physicians are 
mathematically illiterate.” He found that the 
medical establishment was reluctant to publish much of his follow-up work.

In the years afterward, Gatenby moved up the 
ladder to lead the department of diagnostic 
imaging at Fox Chase Cancer Center. He was later 
appointed head of the department of radiology at 
the University of Arizona College of Medicine in 
Tucson, and he continued to garner recognition 
for his skilled interpretation of scans and to 
receive federal grants to study cancer.

Then, in 2007, the Moffitt Cancer Center offered 
Gatenby a job as chair of the radiology 
department. He had a condition: He would come if 
the hospital created a division where he could 
pursue in earnest the link between Darwin’s 
principles and cancer. The Integrated 
Mathematical Oncology Department, born from this 
negotiation, is the first math department in a 
cancer hospital, he says. Finally, Gatenby had a 
place where he could put his ideas to the test.

Gatenby arrives at his corner office at Moffitt 
most days by 7 am. He’s 67 now, and his hair is 
gray at the temples, but his eyebrows are still 
brown. His children­the ones who were napping in 
that hotel room when he jotted down his Darwinian 
inspiration­now have children of their own, and 
he has the  “I Grandpa” coffee mug to prove it. A 
hospital lanyard around his neck, he rolls up his 
crisp shirtsleeves and settles down at his desk. 
Outside his office, roughly 30 scientists and PhD 
students spend their days researching patterns of 
cancer growth using equations like those describing population dynamics.

To Gatenby's knowledge, no one had endeavored to 
exploit evolution against cancer in a clinical 
trial until he developed his prostate cancer 
experiment. He picked prostate cancer to test 
this approach partly because, unlike other 
cancers, a routine blood draw for a molecule 
called prostate-specific antigen (PSA) can offer 
an immediate proxy for the cancer’s progression.

To design a clinical trial, Gatenby and his 
Moffitt collaborators first needed to account for 
their idea that tumor cells vie against each 
other for resources. They turned to game theory 
to plot this dynamic and plugged the numbers into 
the Lotka-­Volterra equations. The computer 
simulations they ran with these equations 
estimated how quickly drug-resistant cells would 
outcompete other tumor cells when exposed to the 
continuous dosage of Zytiga typically given to 
advanced-stage prostate cancer patients.

In the simulations, the typical administration of 
the drug led to drug-resistant cancer cells 
rapidly running rampant. The treatment would 
ultimately fail each time. That bleak outcome 
matched up with the results seen in hospital 
records. In contrast, the computer simulations 
suggested that if Zytiga were administered only 
when the tumor seemed to be growing, then the 
drug-resistant cells would take much longer to 
gain enough advantage to overrun the cancer.

In 2014 the Moffitt team managed to get the first 
small study to test this adaptive therapy 
approach off the ground, recruiting Robert Butler 
and a small group of other men with advanced 
prostate cancer. Butler’s oncologist explained to 
him how it would work. He would remain on the 
Lupron he’d taken for years, and each month he 
would go to the hospital to get his PSA level 
tested, to judge whether his prostate tumor was 
growing. Every three months, he would get a CT 
scan and a full-body bone scan to watch for 
disease spread. Whenever his PSA level edged 
above where it stood when he entered the trial, 
he would start taking the more powerful Zytiga. 
But when his PSA level fell to under half of the 
baseline, he could go without Zytiga. This is 
appealing because Zytiga and drugs like it can 
cause side effects like hot flashes, muscle pain, and hypertension.

The Moffitt approach also promised to be far 
cheaper than taking Zytiga continuously. When 
purchased wholesale, a one-month supply costs 
almost $11,000. Butler had health insurance, but 
even so, his first month’s supply each year would 
set him back $2,700 in out-of-pocket copayments, 
and $400 a month thereafter. Going off the drug 
whenever his PSA level was low would translate to huge cost savings.

“Conceptually it’s a beautifully simple approach. 
He’s turning cancer into a chronic disease.”

Butler was participating in a so-called pilot 
trial, which was less rigorous than a large 
clinical trial, because it didn’t randomly assign 
patients to receive the experimental or standard 
treatments. Rather, the study relied on a group 
of patients treated outside the trial as well as 
results from a 2013 paper on Zytiga to come up 
with a benchmark for how patients typically fare 
when receiving continuous dosing of the drug.

When the early results of their new trial 
trickled in, the Moffitt scientists were 
gratified and relieved. Ahead of the trial, “we 
were, to be honest, terrified,” Gatenby says. The 
benefit of adaptive therapy appeared to be huge. 
Of the 11 men in the study, one left the trial 
after his disease spread, but most were living 
longer than expected without their cancer 
progressing. Men getting continuous dosing of 
Zytiga go a median of 16.5 months before the 
cancer becomes resistant to the drug and spreads. 
In comparison, the median time to progression for 
the men receiving adaptive therapy was at least 
27 months. Moreover, they were on average using 
less than half of the standard amount of Zytiga. 
Joel Brown, an evolutionary ecologist and one of 
Gatenby's collaborators, said the team felt a 
moral obligation to get the word out: “The effect 
was so big that it would be unethical not to report it immediately,” he says.

They published a report in 2017, far earlier than 
anticipated, to a generally positive reaction 
from prostate experts­particularly because it 
suggested a way that people with cancer might 
live longer with less medication. “If you can 
reduce side effects, I think that’s fantastic,” 
says Peter Nelson, an oncologist who studies 
prostate cancer at the Fred Hutchinson Cancer 
Research Center in Seattle. “Conceptually it’s a 
beautifully simple approach.” Jason Somarelli, a 
biologist at the Duke Cancer Institute, calls 
Gatenby a pioneer: “He’s turning cancer into a chronic disease.”

Butler, who is 75, has gone for long periods off 
Zytiga­with stretches lasting as long as five 
months. “I’m now the poster boy, they say,” 
Butler says. He’s one of the best responders in the study.

Some doctors are already trying adaptive therapy 
on patients outside of clinical trials. In 2017 a 
doctor in Oregon, inspired by Gatenby’s pilot 
study, started a prostate cancer patient on a 
modified version of the approach when he refused 
the standard continuous dosing. She has since 
started treating a second man using adaptive 
therapy. Other oncologists might be doing the 
same. It’s nearly impossible to know for sure, 
because adaptive therapy doesn’t require 
government approval. The protocol uses 
already-approved medications, and the 
<>US Food and Drug 
Administration doesn’t police specific dosing schedules.

Experts urge caution, however. The prostate 
cancer study was very small, and without a 
randomly assigned control group the results 
aren’t truly reliable. While the majority of the 
men in the trial remain stable, four more saw 
their cancer progress since the paper came out. 
“This is an approach that now needs to be 
carefully studied in prospective clinical trials 
before it is adopted into clinical practice,” 
says Richard L. Schilsky, chief medical officer 
for the American Society of Clinical Oncology. 
Years could pass before a large-scale test of 
adaptive therapy takes place. Len Lichtenfeld, 
interim chief medical officer of the American 
Cancer Society, echoes Schilsky’s concerns. “Is 
it intriguing? Yes,” Lichtenfeld says. “But there is still a long way to go.”

Gatenby agrees that adaptive therapy needs 
rigorous testing. He conveys a kind of humility 
you don’t see very often in the upper reaches of 
medical science. He told me multiple times that 
he is not an interesting subject to write about, 
and more than once I heard close colleagues 
mangle the pronunciation of his name (which is 
pronounced GATE-en-bee); apparently he had never 
corrected them. But when he believes in 
something, he doesn’t relent. And he believes in 
adaptive therapy. “He’s like a teddy bear, but 
underneath that soft exterior he’s made of 
steel,” says Athena Aktipis, who studies 
theoretical and cancer biology at Arizona State 
University and has collaborated with Gatenby.

Late last year, Gatenby presented his work at a 
meeting of prostate cancer specialists. In the 
question and ­answer session afterward, an 
attendee shared his surprise at the results. “I 
guess what you’re saying is that we’ve been doing 
it wrong all these years,” the man mused, 
according to Gatenby. “I was literally speechless 
for a few moments,” Gatenby admits, “and then I 
said, ‘Well, yeah, I guess that’s what I’m 
saying.’” He is still dwelling on the exchange 
and wishes he could somehow find the man and 
apologize. He’s not taking back what he said; he 
does think the profession can do better. But, he 
says, “I should have been more diplomatic.”

In 2016, a couple dozen researchers gathered in a 
conference room at an ultramodern genetic 
sequencing center along the banks of the River 
Cam, 9 miles outside of Cambridge, England. The 
gathering brought together experts to discuss how 
principles of ecology might apply to cancer. When 
they took a break, their idea of fun was to play 
a round of “Game of Clones,” in which a small 
group of scientists pretended to be cancer cells 
trying to persuade the maximal number of other 
researchers bouncing around the room to be their malignant clones.

During this meeting, one overarching theme kept 
popping up: Evolution doesn’t operate the same 
way within all cancers. It’s not even clear that 
Darwinian natural selection always determines the 
genetic mutations that abound within a tumor. A 
study of colon cancer samples conducted by one of 
the conference attendees, Andrea Sottoriva of the 
Institute of Cancer Research in London, and 
Christina Curtis, a computational biologist at 
Stanford University, suggested a different pattern.

When colorectal tumors begin to form, there seems 
to be a “big bang” of mutations. This initial 
explosion of cellular diversity in these colon 
cancers seems to be followed by a period in which 
random genetic changes arise and become more 
prevalent out of pure happenstance rather than 
because the mutations confer some sort of 
competitive advantage. It’s still unclear whether 
adaptive therapy, which operates on the 
assumption that there’s Darwinian competition 
between tumor cells, would work well for cancers 
where the mutations arise continuously by chance.

Still, a kind of consensus emerged, and a year 
after the Cambridge meeting, the organizers 
published a statement outlining how cancers might 
be better classified. Twenty-two researchers­some 
of the biggest names in the field of evolutionary 
oncology, including Gatenby­coauthored the document.

One important factor in the group’s suggested 
classification scheme is a measure of how swiftly 
a cancer is mutating. In the past decade, faster 
DNA sequencing tools have shown that 
Nowell­Gatenby’s old professor, the 
­cigarette-smoking pioneer in applying 
evolutionary thinking to cancer­was prescient: 
Individual tumors often bristle with rapid-fire 
genetic changes. Rather than two or three initial 
errors setting off a chain of uncontrolled 
growth, many tumors are the result of several 
series of mutations. A significant experiment 
published in 2012 found at least 128 different 
DNA mutations in various kidney tumor samples 
from one patient, for instance. There's some 
evidence that the more mutations there are, the 
more aggressive a cancer tends to be, suggesting 
a higher chance that one of these DNA changes 
will confer tumor cells with the potential to be 
drug-resistant. Given technological advances, 
it’s not too far-fetched to think that within the 
coming decade, doctors will routinely measure the 
amount of mutations in their patients’ tumors.

Today most cancers are assessed using a system 
that dates back to the 1940s. Doctors typically 
evaluate factors such as whether a cancer has 
spread to lymph nodes or beyond and on the basis 
of these attributes determine its “stage.” On one 
end of the spectrum are stage 1 cancers, which 
are relatively confined, while at the other end 
are stage 4 cancers, which have spread 
extensively. Crucially, this system of assigning 
cancer a stage doesn’t formally take a cancer’s genetic mutations into account.

The suggested categorization system that grew out 
of the Cambridge meeting would look at cancer in 
a completely new way. Rather than four stages of 
cancer, the authors of the 2017 consensus 
statement propose no less than 16 different 
categories­for example, tumors that have slow 
cell turnover and a low rate of accumulating 
mutations, or tumors that are a hotbed of genetic 
diversity with quickly replicating cells 
competing for resources. This latter type of 
tumor might be the most likely to evolve a way to 
outcompete drug-sensitive cells in the body and 
thereby could, in some cases, be the most 
dangerous. A fast-­moving cancer of this kind 
might also be the best candidate for adaptive therapy.

Around the time the consensus statement came out, 
Gatenby and his collaborators in Tampa were hard 
at work running cell experiments in a lab down 
the hall from his office. The goal was to prove a 
key tenet of adaptive therapy. Gatenby’s approach 
assumes that when treatment is removed, 
drug-resistant cancer cells will replicate more 
slowly than drug-sensitive cells. The theory 
rests on the assumption that those resistant 
cells need lots of energy to maintain their armor 
against the medication meant to kill them. During 
treatment breaks, the thinking goes, the 
fuel-hungry resistant cells are outcompeted by 
drug-­sensitive cells, which need fewer resources to thrive.

To gather evidence for this idea, Gatenby’s 
research team placed human breast cancer cells 
with resistance to the drug doxorubicin in a 
petri dish alongside an equal-size population of 
doxorubicin-sensitive breast cancer cells and 
watched the two groups fight for resources. By 
day 10 the resistant cells made up only 20 
percent of the cells in the dish and continued to 
slowly decline from there. At the end of the 
experiment, published last year, these resistant 
cells had dropped to around 10 percent of the total population.

Granted, this experiment happened in a petri 
dish, not a human body­or even the body of a lab 
rat. Some leading cancer specialists agree with 
Gatenby that drug-­resistant cells are likely 
outcompeted by other cells when cancer medication 
is withdrawn. But, say others, what if Gatenby is 
wrong? What if resistant cells actually thrive 
during the period when the patient is taken off 
drugs? The risks are high. No one wants to hasten death.

Rethinking cancer as a chronic illness requires a 
mental shift­a shift that other changes in cancer 
therapy might be easing. There’s a practice of 
letting cancer patients take doctor-supervised 
“drug holidays” from their medications, for 
instance. And we’ve adapted our thinking when it 
comes to medicine before. Doctors once thought 
that stress was the primary culprit behind 
ulcers, but biologists uncovered a bacterium as 
the main cause. More recently we’ve gotten used 
to the weird idea that trillions of bacteria live in our gut microbiome.

Perhaps, then, it isn’t a huge stretch to think 
we might tolerate coexisting with cancer cells as 
long as we can prevent them from growing 
unchecked. Whereas Darwin put forth ideas about 
what has become known as macro­evolution­the rise 
and fall of species, whether they be beetles or 
bald eagles­this new view of cancer could be an 
example of what we might call “endo-­evolution”: 
natural selection playing out within an organism’s own tissues.

The American Cancer Society acknowledges that 
some cancers are already managed as chronic 
illnesses. In certain cases, doctors simply try 
to keep the malignancies from spreading with new 
rounds of medication. Gatenby’s adaptive therapy 
aims to take the guesswork out of the treatment. 
More trials at Moffitt are in the planning stages 
or underway for cancers affecting the breast, 
skin and thyroid, in addition to a new, bigger 
trial in prostate cancer patients. Across the 
country, in Arizona, Athena Aktipis and her 
husband and scientific collaborator, Carlo Maley, 
have secured a grant to begin a breast cancer 
trial using adaptive therapy in conjunction with 
a local branch of the Mayo Clinic.

It isn’t a huge stretch to think we might 
tolerate coexisting with cancer cells as long as 
we can prevent them from growing unchecked.

But the idea of cancer as an implacable enemy 
that needs to be annihilated runs deep. Even 
Gatenby feels it, particularly when it comes to 
children. When his daughter was a teenager, one 
of her classmates died from a form of cancer 
called rhabdomyosarcoma. He never met his 
daughter’s friend but heard about his decline. 
Then, last year, a pediatric oncologist at 
Moffitt approached him to see if therapy inspired 
by evolutionary theory might work to fully weed 
out cancer from children newly diagnosed with 
that same disease. In the highest-risk group, 
that cancer kills as many as 80 percent of patients within five years.

In October, they met to begin designing a study. 
This trial will use a more sophisticated 
evolutionary model to cycle patients on and off 
of several drugs. The hope is to deploy the 
additional drugs to kick the cancer while it’s 
down, and thereby drive it to extinction. It’s an ambitious goal.

For now, Gatenby is most focused on managing 
advanced cancers in adults, and doing so as a 
chronic disease. In that sense, he’s challenging 
the words emblazoned on the outside wall of the 
Moffitt Cancer Center: “To contribute to the 
prevention and cure of cancer.” Robert Butler has 
pondered these words too, which he passes when 
walking into the building for checkups and 
treatments. “Certainly, in my case there’s no 
intention of cure. What we’re doing is control. 
So that’s not really the correct logo anymore, is 
it?” he says. Butler tells me about a time when 
he and some of the Moffitt researchers 
brainstormed alternative slogans. “We finally 
came up with ‘Our aim is to make you die of 
something else’­which I thought was lovely,” he adds. “It’s more true.”

Roxanne Khamsi 
<>(@rkhamsi) is a 
science writer living in New York and chief news 
editor of <>Nature Medicine.
This article appears in the April issue