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Defeating cancer could be mission impossible
By Robert A Gatenby |
August 28, 2009, Friday
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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.
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 make the problem worse.
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 1980s, 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 a threshold level, with the goal of producing a sustainable and satisfactory crop.
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 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. 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.
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.
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.
(The author is chairman of Radiology and Integrated Mathematical Oncology at the H. Lee Moffitt Cancer Center. Copyright: Project Syndicate, 2009. www.project-syndicate.org.)
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.
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 make the problem worse.
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 1980s, 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 a threshold level, with the goal of producing a sustainable and satisfactory crop.
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 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. 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.
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.
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.
(The author is chairman of Radiology and Integrated Mathematical Oncology at the H. Lee Moffitt Cancer Center. Copyright: Project Syndicate, 2009. www.project-syndicate.org.)
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