Does “Curing” Cancer Kill Patients?

by Robert A. Gatenby

Robert A. Gatenby is Chairman of Radiology and Integrated Mathematical Oncology at the H. Lee Moffitt Cancer Center.

TAMPA - Patients and politicians increasingly demand a "cure" for cancer. But controlling the disease may prove to be a better strategy than striving to cure it.

A century ago, the German Nobel laureate Paul Ehrlich introduced the concept of "magic bullets" - compounds engineered to target and kill tumor cells or disease-causing organisms without affecting normal cells. The success of antibiotics 50 years later seemed to validate Ehrlich's idea. So influential have medicine's triumphs over bacteria been that the "war on cancer" continues to be driven by the assumption that magic bullets will one day be found for tumor cells if the search is sufficiently clever and diligent.

Yet lessons learned in dealing with exotic species, combined with recent mathematical models of the evolutionary dynamics of tumors, indicate that eradicating most cancers may be impossible. Trying to do so, moreover, could worsen the problem.

In 1854, the year Ehrlich was born, the diamondback moth was first observed in Illinois. Within five decades, the moth had spread throughout North America. It now infests the Americas, Europe, Asia, and Australia. Attempts to eradicate it using chemicals worked only fleetingly. In the late 1980's, biologists found strains that were resistant to all known insecticides.

So farmers abandoned their efforts to eliminate the moth. Instead, most now apply insecticides only when infestation exceeds some threshold level, with the goal of producing a sustainable and satisfactory crop. Under the banner of "integrated pest management," hundreds of invasive species are now successfully controlled by strategies that restrict the population growth of pests but do not attempt to eradicate them

The ability of tumor cells to adapt to a wide range of environmental conditions, including toxic chemicals, is similar to the evolutionary capacities demonstrated by crop pests and other invasive species. As in the case of the Diamondback moth, successful eradication of disseminated cancer cells is rare. But despite the paucity of success, the typical goal in cancer therapy remains similar to that of antimicrobial treatments - killing as many tumor cells as possible under the assumption that this will, at best, cure the disease and, at worst, keep the patient alive for as long as possible.

Some types of cancer - for example, Hodgkin's lymphoma, testicular cancer, and acute myeloid leukemia - can be consistently cured using aggressive chemotherapy. But these malignant cells seem to be particularly responsive to "treatment." Just as invasive species adapt to pesticides, most cancer cells adapt to therapies. Indeed, the parallels between cancerous cells and invasive species suggest that the principles for successful cancer therapy might be found not in the magic bullets of microbiology but in the evolutionary dynamics of applied ecology.

Recent research suggests that efforts to eliminate cancers may actually hasten the emergence of resistance and tumor recurrence, thus reducing a patient's chances of survival. The reason arises from a component of tumor biology not ordinarily investigated: the cost of resistance to treatment.

Cancer cells pay a price when they evolve resistance to chemotherapy. For example, to cope with toxic drugs, a cancer cell may increase its rate of DNA repair, or actively pump the drug out across the cell membrane. In targeted therapies, in which drugs interfere with the molecular signaling needed for proliferation and survival, a cell might adapt by activating or following alternative pathways. All these strategies use up energy that would otherwise be available for invasion into non-cancerous tissues or proliferation, and so reduce a cell's fitness.

The more complex and costly the mechanisms used, the less fit the resistant population will be. That cancer cells pay a price for resistance is supported by several observations. Cells in laboratory cultures that are resistant to chemotherapies typically lose their resistance when the chemicals are removed. Lung cancer cells that are resistant to the chemotherapy gemcitabine are less proliferative, invasive, and motile than their drug-sensitive counterparts.

Although resistant forms are commonly found in tumors that haven't yet been exposed to treatment, they generally occur in small numbers. This suggests that resistant cells are not so unfit that drug-sensitive cells completely out-competed them, but that they struggle to proliferate when both types are present.

Our models show that in the absence of therapy, cancer cells that haven't evolved resistance will proliferate at the expense of the less-fit resistant cells. When a large number of sensitive cells are killed, say, by aggressive therapies, resistant types can proliferate unconstrained. This means that high doses of chemotherapy might actually increase the likelihood of a tumor becoming unresponsive to further therapy.

So, just as judicious use of pesticides can control invasive species, a therapeutic strategy designed to maintain a stable, tolerable tumor volume could improve a patient's prospects for survival by allowing sensitive cells to suppress the growth of resistant ones.

To test this idea, we treated a human ovarian cancer, grown in mice, with conventional high-dose chemotherapy. The cancer rapidly regressed but then recurred and killed the mice. Yet when we treated the mice with a drug dose continuously adjusted to maintain a stable tumor volume, the animals, though not cured, survived for a prolonged period of time.

Designing therapies to sustain a stable tumor mass rather than eradicate all cancer cells will require a strategy that looks beyond the immediate cytotoxic effects of any one treatment. Researchers will need to establish the mechanisms by which cancer cells achieve resistance and what it costs them. They will need to understand the evolutionary dynamics of resistant populations, and design strategies to suppress or exploit the adapted characteristics.

Of course, cancer researchers should not abandon their search for ever-more-effective cancer therapies, even for cures. But it may be time to temper our quest for magic bullets and recognize the cold reality of Darwin's evolutionary dynamics. Medicine's goal of a glorious victory over cancer may need to yield to our recognizing that an uneasy stalemate may be the best that can be achieved.

Copyright: Project Syndicate, 2009.


This article is brought to you by Project Syndicate that is a not for profit organization.

Project Syndicate brings original, engaging, and thought-provoking commentaries by esteemed leaders and thinkers from around the world to readers everywhere. By offering incisive perspectives on our changing world from those who are shaping its economics, politics, science, and culture, Project Syndicate has created an unrivalled venue for informed public debate. Please see:

Should you want to support Project Syndicate you can do it by using the PayPal icon below. Your donation is paid to Project Syndicate in full after PayPal has deducted its transaction fee. Facts & Arts neither receives information about your donation nor a commission.



Browse articles by author

More Current Affairs

Added 12.07.2018
The cabinet members who resigned this week apparently feared that politics is taking May toward a “soft Brexit,” their worst of all possible worlds........“soft Brexit,” maintains the status quo, more or less, letting Europeans freely circulate into British labor markets and allowing European firms to operate easily in the UK. The problem with “soft Brexit” is that it raises questions about why the UK is leaving at all, since it will still have the same obligations to Europe as before, it just won’t have a voice when the remaining 27 members of the European Union meet to make decisions.
Added 12.07.2018
One study on the 2010 World Cup found that there was a 37.5% rise in admission rates across 15 accident and emergency departments on England match days........Examining reports of domestic abuse in Lancashire (a county of approximately 1.5m people in Northern England), across the 2002, 2006 and 2010 World Cup tournaments, we discovered a 26% increase in reports of domestic abuse when England won or drew, and a 38% increase when England lost. Reports were also more frequent on weekends, and reached their peak when England exited the tournament.
Added 10.07.2018
If, back in the 1980s and 1990s, the US government, rather than arguing for Chinese economic opening, had prohibited any US company from investing there, China’s rise would have been significantly delayed, though not permanently prevented. Because that did not happen, China’s rise is now self-sustaining. A huge and increasingly affluent domestic market will make exports less vital to growth.
Added 10.07.2018
Comparing today’s demagogues with Adolf Hitler is almost always unwise. Such alarmism tends to trivialize the actual horrors of the Nazi regime, and distracts attention from our own political problems. But if alarmism is counterproductive, the question remains: At what point are democracies truly in danger? What was unimaginable only a few years ago – a US president insulting democratic allies and praising dictators, or calling the free press “enemies of the people,” or locking up refugees and taking away their children – has become almost normal now. When will it be too late to sound the alarm?
Added 09.07.2018
In view of such actions, expectations for Trump’s behavior at the upcoming summit have gone from prickly to dangerous. The sense of foreboding has been heightened by the announcement that, just four days after the summit ends, Trump will meet with Russian President Vladimir Putin, in Helsinki. The nightmare scenario is easy to imagine: Trump lays bare NATO’s fractures, including by questioning mutual defense, before selling his allies down the river by publicly embracing Putin. But this does not need to be the outcome.
Added 09.07.2018
After 2027 (or maybe even 2025, only 7 years from now), the number of EVs will rapidly accelerate, as virtually all new vehicles bought will be electric (an effect of rapidly falling battery and other component costs and of the fuel for electric cars being essentially free; you can power one off your rooftop solar array).
Added 03.07.2018
Most pundits interpret Trump’s outbursts as playing to his political base, or preening for the cameras, or blustering for the sake of striking future deals. We take a different view. In line with many of America’s renowned mental-health experts, we believe that Trump suffers from several psychological pathologies that render him a clear and present danger to the world.
Added 03.07.2018
In the United Kingdom, Brexit looms large, with everyone from government ministers to tabloid newspapers frothing daily about the deal that will be struck with the European Union and the effects that it will have. But the EU faces too many pressing challenges to be obsessing about Britain. The UK’s concern is understandable: evidence is mounting of the likely damage a departure from the single market and customs union will do to the UK economy. According to new research from the Centre for European Reform, the UK economy is already 2.1% smaller than it would have been had voters chosen to remain. The hit to public finances totals £440 million ($579 million) per week.
Added 26.06.2018
Nowadays, Britain’s words and actions on the world stage are so at odds with its values that one must wonder what has happened to the country. Since the June 2016 Brexit referendum, British foreign policy seems to have all but collapsed – and even to have disowned its past and its governing ideas. Worse, this has coincided with the emergence of US President Donald Trump’s erratic administration, which is pursuing goals that are completely detached from those of Britain – and of Europe generally. 
Added 26.06.2018
With each passing day, it becomes increasingly evident that US President Donald Trump’s administration cares less about economics and more about the aggressive exercise of political power. This is obviously a source of enormous frustration for those of us who practice the art and science of economics. But by now, the verdict is self-evident: Trump and his team continue to flaunt virtually every principle of conventional economics.
Added 26.06.2018
The sights and sounds of Central American children being ripped from their parents by US Border Patrol officers have, by now, spread across the globe. The experience has been traumatizing to its victims and deeply painful to watch. It has also done incalculable damage to the very idea of America. This is June when we are supposed to be celebrating "Immigrant Heritage Month". Each year, I have taken this opportunity to recall my family's immigrant story - the opportunity and freedom they sought, the hardships they endured, and the remarkable progress they made in just one generation. 
Added 24.06.2018
State terrorism comes in many forms, but one of its most cruel and revolting expressions is when it is aimed at children. Even though U.S. President Donald Trump backed down in the face of a scathing political and public outcry and ended his administration’s policy of separating migrant children from their parents, make no mistake: His actions were and remain a form of terrorism.
Added 22.06.2018
It is now clear that the twenty-first century is ushering in a new world order. As uncertainty and instability associated with that process spread around the globe, the West has responded with either timidity or nostalgia for older forms of nationalism that failed in the past and certainly will not work now. Even to the most inveterate optimist, the G7 summit in Quebec earlier this month was proof that the geopolitical West is breaking up and losing its global significance, and that the great destroyer of that American-created and American-led order is none other than the US president. To be sure, Donald Trump is more a symptom than a cause of the West’s disintegration. But he is accelerating the process dramatically.
Added 20.06.2018
Sessions quoted a line written by the apostle Paul to a small community of Christians living in Rome around 55AD to defend the Department of Justice’s approach. He said: "I would cite you to the Apostle Paul and his clear and wise command in Romans 13, to obey the laws of the government because God has ordained them for the purpose of order." Sessions used the Bible because one of the most vocal opponents of the crackdown on asylum cases has been the Catholic Church. It’s no surprise that Sessions appealed to Romans chapter 13 verse 1 in response: not only did he hope to undermine Catholic authority by using the Bible against them, he cited a statement so broad that one might use it to defend anything a government does, good or bad. Picture below St Paul writing his epistles, by Valentin de Boulogne, via Wikimedia Commons.
Added 19.06.2018

I find it exceptionally irritating when I hear liberals worry about whether Israel will be able to remain a "Jewish and Democratic State" if it retains control of occupied Palestinian lands.

Added 18.06.2018
Daniel Wagner: "My prediction Korean War will be formally ended, the peninsula will be denuclearised, and a lasting peace will be the result."
Added 14.06.2018
Extract: PiS [ the ruling Law and Justice party] has established the most significant addition to the Polish social safety net since 1989: the Family 500+ program. Launched in 2016, Family 500+ embodies the nationalism, traditional family values, and social consciousness that the PiS seeks to promote. The program pays families 500 złoty ($144) per month to provide care for a second or subsequent child...........The program has been enormously popular. Some 2.4 million families took advantage of it in the first two years. The benefit, equivalent to 40% of the minimum wage, has almost wiped out extreme poverty for children in Poland, reducing it by an estimated 70-80%........... Liberal pro-European politicians and policymakers are not convinced. They complain that such a generous family benefit will weaken work incentives and blow up the government budget. But initial evidence suggests that Family 500+ has actually increased economic activity. It has also reversed the post-communist decline in fertility, increased wages (particularly for women), and enabled families to buy school materials, take vacations, buy more clothes for their kids, and rely less on high-priced credit for basic household needs. And, thanks to rapid economic growth, the government deficit has steadily fallen, not grown.
Added 12.06.2018
The depths of hypocrisy of the Republican Party in supporting Trump’s meeting with the North Korean dictator in Singapore are hard to plumb. This is a party whose leading members adopted the Ostrich Foreign Policy Principle for decades. If you don’t like a country’s government or political and economic system, pretend it does not exist.
Added 12.06.2018
US Defense Secretary Jim Mattis has spoken out against China’s strategy of “intimidation and coercion” in the South China Sea, including the deployment of anti-ship missiles, surface-to-air missiles, and electronic jammers, and, more recently, the landing of nuclear-capable bomber aircraft at Woody Island. There are, Mattis warned, “consequences to China ignoring the international community.” But what consequences?
Added 12.06.2018
With a general election approaching in September, Swedish voters are being warned that now it’s their turn to be targeted by Russian interference in the democratic process. According to Sweden’s Civil Contingencies Agency (MSB), which is leading the country’s efforts to counter foreign-influence operations, such interference is very likely, and citizens should be on the lookout for disinformation and fake news.