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How to win the war against cancer

The power of massive, integrated programs must be brought to bear

By | November 5, 2008

Editor's note: After a decades-long war against cancer, experts are calling for new ways to approach the disease. The following is an opinion article running in our December issue, which we are running early to stimulate discussion online. After tens of billions of US federal dollars (plus billions more from private sources) and nearly 40 years of aggressive research, the war on cancer is depressingly far from over. Cancer will soon become the leading cause of death in America, passing heart disease. At some point in their lives, 43% of the public will get some form of cancer. Progress has been made, however. Age-adjusted rates for those who develop cancer are down, and survival rates have increased. Knowledge of the molecular and genetic mechanisms has increased significantly. Strategies for targeting therapies selectively to tumors are becoming increasingly available. We also know more about how diet and other lifestyle choices, as well as family history, affect the chances that individuals will have cancer. But we have so much more to learn. For moral, emotional and economic reasons, fighting the war on cancer remains a top priority. But we've got to change our strategy. The federal cancer research strategy resembles the way in which major new weapons systems are built, with pieces farmed out to as many congressional districts as are needed to assemble the requisite support for them in Congress. Although cancer research funding is peer reviewed, it still is spread across numerous universities throughout the nation. Whether or not politics explicitly infects the grant-making process, the result is a highly fragmented research effort. We now know from many areas of science -- including cancer research -- that collaborative research by investigators with different but complementary areas of expertise are more likely to crack difficult problems than "lone rangers" who work in isolation. With more cooperation and less competition in cancer research, the war against cancer is much more likely to be won. This fundamental insight has been recognized by one leading cancer research advocacy group, Stand Up To Cancer (SU2C) which funds research that seeks to translate basic science results into therapies. SU2C hands out money for cancer research on the condition that grant recipients demonstrate collaboration. This cooperative approach is also the premise of MIT's new $100 million David H. Koch Institute for Integrative Cancer Research that is bringing together biologists, chemists, and nanotech engineers. It is now time for the federal government to apply a similar approach. We propose that the National Cancer Institute reorganize its research program to solicit competitive grant proposals from consortia of research centers. Funding would become much more highly concentrated than it is now. For example, about 75% of the $4.8 billion NCI budget for 2008 will be spent on 60 Comprehensive Cancer Centers, 50 Specialized Programs of Research Excellence (SPOREs) and numerous other research grants and programs. NCI could realign these into three or four comprehensive regional cancer efforts that take a comprehensive approach to converting knowledge about cancer into diagnostics and therapies, one that involves researchers from multiple disciplines inside and outside traditional medicine, and both academia and industry. We suggest the following criteria for making the awards: • The breadth of expertise represented by the consortia • Emphasis on translating basic scientific knowledge into potential diagnostics, therapies, or prevention strategies • Academic-industry collaborations • Preference for programs that integrate at least three of the following disciplines: Molecular biology, Chemistry, Engineering, Systems Biology, Clinical Pharmacology, Genomics and Information Technology • Matching funds from private or from other public sources (state and/or municipal/county governments) • Mechanisms for commercialization of products Only by concentrating cancer research efforts will it be possible to avoid delays in discovery and translation. Scaling also should facilitate standardization of methods, implementation of electronic and personal health care records and counseling of families, based on genetic information. Let's get on with this new strategy. Too many lives hang in the balance. Frank Douglas is a Partner at Puretech Ventures and a Senior Fellow at the Kauffman Foundation. Robert E. Litan is Vice President for Research and Policy at Kauffman and a Senior Fellow at the Brookings Institution. mail@the-scientist.com
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Comments

Avatar of: David Bird

David Bird

Posts: 4

November 6, 2008

I disagree the claim that the authors make that "big science" is better science. As well, there are two assumptions that the authors of this article seem to hold, without any justification as to why one should accept them:\n\n1. The "war" on cancer is not advancing as quickly as it could be. The progress of 50+ years and billions of dollars could be greatly improved.\n\nCancer is intrinsically connected with perhaps the most complicated biological processes - growth and development. It is arrogance (and perhaps somewhat of a slight to the researchers in the field) to suggest that the current rate of progress is retarded in someway compared to other approaches. \n\n2. Involving industry in direct partnership will accelerate the time-to-market of new discoveries. On the contrary, there are many examples in biotechnology where self-interest motivates control of intellectual property to the detriment of the greater good. \n\nWhile I do agree that interdisciplinary-disciplinary collaboration can lead to great advances, to dismiss the efforts of smaller groups or individuals as "...'lone rangers' who work in isolation..." demonstrates willful or naive ignorance of the historical record. How many of the greatest advances in molecular biology were achieved by a consortium of scientists pressed into a collaboration? Fewer than the discoveries made by the intense focus of a few individuals I would argue. Collaboration is essential; forced collaboration - making funding conditional based on fitting to a mold based on flawed assumptions - will not advance the "war" any faster.\n
Avatar of: anonymous poster

anonymous poster

Posts: 125

November 6, 2008

"Whether or not politics explicitly infects the grant-making process, the result is a highly fragmented research effort." \n\nI've been in the academia long enough as a doctoral student, alone, to see all too clearly that the so-called research professors, i.e., principal investigators, are motivated far more by their own personal financial gains, recognitions, and petty egos than by their desire or moral responsibility to advance the treatment or cure of cancer, despite their vehement denial. There are too much selfishness and distrust within the dysfunctional, cut-throat, competitive, medical research environment to encourage and foster collaborations or cooperations even within the individual research labs, much less across those. It really would take lots of threats or arm-twisting to force cooperations among all the stubbornly arrogant and egotistical researchers who are typically asocial people who care more about beating others to become the sole winners of Nobel Prize than to willingly compromise for the common goal of defeating cancer or other major diseases. And the rest of world wonders why the progress has been so slow in coming? It certainly wasn't only because the science is so hard!
Avatar of: Olga Beliak

Olga Beliak

Posts: 1

November 6, 2008

My research and experience tell me that chemo is a wrong direction for most if not all cancers. One day it will become history like blood letting and purgatives. Cancer is not a one step problem. Attempt just to kill cancer cells goes nowhere. Scientists need to employ multistep problem solving skills. \n\nOlga Beliak, Naturopath
Avatar of: David Clark

David Clark

Posts: 4

November 6, 2008

The war on cancer has been running longer than the war in Iraq and with about as much success. It is remarkably interesting how the vested interests of the cancer research industry resemble those of the military.
Avatar of: anonymous poster

anonymous poster

Posts: 125

November 6, 2008

change your attitude - and that would require a really hard effort, gentlemen! \n\n==============================================================================================================\nFor moral, emotional and economic reasons, fighting the war on cancer remains a top priority. But we've got to change our strategy.\n==============================================================================================================\n\n \n
Avatar of: ELLEN ZWARTHOFF

ELLEN ZWARTHOFF

Posts: 1

November 7, 2008

In my view the approach Dr. Douglas proposes will not work for the following reasons:\n1) forcing collaboration is not going to work because people need to trust each other to be able to work together and share the revenues. This is already difficult enough in normal life (look around in your family and circle of friends)and numerous examples of irreconsilable conflicts exist in cases where this was demanded at work. \n2) creating huge centers wich huge amounts of money will decrease competitiveness and hence quality will suffer.\nOne important thing where topdown money will help, is to facilitate the generation of biobanks with fresh and FFPE tissue and blood in combination with regularly updated databases with clinical data (patients stays anonymous)and a long follow-up. This is imperative for testing of biomarkers regarding prediction of prognosis as well as prediction of response to a certain treatment. \n\n
Avatar of: Rainer Zahlten

Rainer Zahlten

Posts: 3

November 7, 2008

This "new" strategy is bound to fail. Why? Because enforced cooperation for the sake of obtaining research grants is counterproductive to a physiologic matching of research interests, including a viable chemistry between participating scientists. The European grant programs for cooperative research, based on the same intentions as described by the authors, have not only turned out to be burocratic nightmares but also fostered wrong motivations for collaborations. There are already numerous cooperative cancer programs in the US, Europe and Asia which take advantage of the great diversity of expertise, focus and motivation without major governmental interference. I am convinced that in the end of the day the support of international cooperative research efforts, based on the parallel processing of best research brains, will synthesize new breakthrough ideas which will be quantum jumps for new progress in cancer research. Since governmental financial resources are tax payers money, participation of pharmaceutical industry in cost sharing and product realisation are obviously highly desirable. Although concentration of research efforts through government driven programs appear attractive, the inherent competitive spirit of scientists, fertilized by whatever motivation, remains a mandatory component of success. Shifting the balance towards overbearing concentration in research will cut the wings of creative ideas to fly. Grant support for infrastructure management of existing cooperative cancer research organizations would greatly facilitate operations and enhance research efficiency by generating creative research time for participating scientists who are overburdened already by burocratic tasks.
Avatar of: anonymous poster

anonymous poster

Posts: 15

November 7, 2008

The creative solutions needed for a "cure for cancer" requires out-of-box thinking and not just a more efficient mechanism for taking what we know to the bedside. This is best fostered by supporting the "lone ranger", not large armies of workers of different flavors "managed" by a few senior leaders whose ideas will bottle neck the thinking and worse still eat away the little resources needed for pioneers to truly make breakthroughs. The funding mechanisms that encourage creativity and risk taking such as the new Pioneer awards, EUREKAs,T-RO1s, CEBRAs etc need to be expanded and will bear fruit. Cooperation among these pioneers can then be encouraged by various forms of program grants that encourage cooperation among the lone rangers where ever they are in the country and only when it seems appropriate and comes naturally. It is counter productive to put all your eggs in a few baskets.
Avatar of: Tammy Koch

Tammy Koch

Posts: 1

November 7, 2008

How could nutrition and the biologic impact of commercial environmental chemicals be left out of the criteria for research dollars? Sometimes in the quest and wonderment of science....and much of the research to date is amazing, the big picture of how the human body heals is lost. It takes discipline and skill to take the scientific advances and apply them to practice that will advance cancer research. Also, interesting to note that one of the criteria is bound to commercialization...even with a disease as devastating as cancer a criteria such as this proves that health care and capitalism are a powerful handshake. Maybe that is why the US still ranks so low in world health care statistics?
Avatar of: Seybert James

Seybert James

Posts: 4

November 7, 2008

It's sad to note that the calls for an integrated approach over the past few decades have never been heeded. Given that the members of Congress often value tenure in office over the general welfare of the country, it will indeed take some creative thinking to develop centers of integration that will be eligible for major, centralized funding. Perhaps one or more of the national laboratories could fill this role, acting as centers where resident and visiting scientists can interact.\n\nUnfortunately, with many national labs being administered by universities or having strong univeristy links, the tendency to preserve information as confidential for patent purposes will continue. In addition, the research community will have to change its own way of thinking and become more open to sharing of research in progress instead of tenaciously protecting data so one person or team can have the "academic honor" of first publication.
Avatar of: anonymous poster

anonymous poster

Posts: 125

November 7, 2008

It's been some two decades, I think, since it was created with the goals stated by the authors in mind, but I rarely heard of any big breakthrough in cancer treatment coming out from there. It seems more like the Devil's Triangle where millions of public and private dollars disappeared, instead....
Avatar of: WILL BARGMANN

WILL BARGMANN

Posts: 1

November 7, 2008

Basic modeling in cancer research was greatly enhanced with the groundbreaking work by Varmus and Bishop\n"for their discovery of the cellular origin of retroviral oncogenes". I was privileged to meet both prior to their Nobel award when I was a technician working at UT Austin in the lab of Henry Bose. He predicted their Nobel prize 4 years prior to the award in 1989. Our small lab has received nearly 30 years of continuous NCI support that has allowed the training of both graduate and undergraduate students in molecular biology focused on the v-Rel oncogene's capacity to transform cells of avian origin. The authors of this proposal would gut the capacity of our academic program to be able to fund basic cancer research at this level. It has become increasingly difficult to land and maintain NCI support in the current funding environment. I cannot imagine how much damage would be done to basic research should the author's proposal be implemented. \n
Avatar of: anonymous poster

anonymous poster

Posts: 15

November 7, 2008

To win the war on cancer, we need to get away from the mantra of more translational science in giant Walmart-like operations espoused by these authors and other clinicians and clinical scientists and move the problem to our counterparts in the basic biological, physical and engineering science disciplines. \n\nAll we really need to do is to make highly sensitive sentinels of abnormal cell growth that can hone in on cancerous cells before they metastasize and combine that with laser or nano-technology based ablation strategies to obliterate these cells. The current potpurri of chemotherapy, radiation therapy, inhibitors of various cell surface growth factor receptors, DNA chips with expression signatures of tumors etc are all inelegant and sledge hammer solutions that are bound to fail, like they have for the past 50 years, because they are fundamentally reactive solutions, not preemptive ones. \n\nOpen up the competition for the best ideas from ANYBODY who can partner with their appropriate counter parts ANYWHERE to produce the imaging tools to detect cancerous cells very early and sensitively and find ways to precisely guide ablation techniques to selectively fry those cells! Wasting more money on pork barrel comprehensive cancer centers (existing or new)to win the war on cancer is not the way to go.
Avatar of: anonymous poster

anonymous poster

Posts: 5

November 10, 2008

I agree with some previous posters that forced collaborations are not going to work in academic environment just because all career decisions are made based on individual achievements of the researcher and not on their collaborative spirit. A bright postdoc will not want to participate in a project where he/she can at most count on being one of twenty coauthors in a paper, even if it were an NEJM paper. For them only first/last authorship counts as far as their further career goes. The same thing goes for PIs - their future grant support and advancement in the ranks of the University will depend much more on their individual performance than their collaborative efforts. It is the industry where collaboration is preferred over competition and where it works fine. The industry, however, as one of the previous posters noted, has its own set of rules, some of which go against the broad public good. Therefore big bucks should be spent by the NIH on big projects, but these projects should have a purely supportive role (core facilities, tissue banks, high-throughput assay systems, result databases) and the people involved should be paid enough to make up for decreased career opportunities, which working in such supportive roles would entail. Enticing people to collaborate just because there is money in collaborating is going to just result in a lot of people flocking around the trough and pretending they have some common goal, while in fact they will be doing disparate things under a makeshift common banner.

November 13, 2008

Cancer research needs a change of paradigm. The current one holds that cancer is a disease of one or few cells that accumulate genetic or epigenetic mutations, leading to loss of control of proliferation, cellular death and adhesion signaling pathways. This particular model has brought us an amazing understanding of some aspects of this disease. But it is not good enough to lead us to a cure.\nSeveral studies published since the beginning of modern cancer research do not fit into expected results according to the current paradigm. For example, a very recent article published in the New England Journal Of Medicine (N Engl J Med 359:1995, November 6, 2008)showed that "Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival". This is one of many examples indicating that more than "just" neoplastic cells are contributing to the morbidity and mortality of the disease. Cancer is a disease of the whole individual and not (exclusively) of a few initial cells. \nTumor immunology research also fails to provide the expected answers according to the current immunology paradigm. After decades of getting the "wrong" answers maybe it is time to change the model to accommodate these unexpected results...\nBrute force strategies like the ones suggested in Douglas and Litan's article will not help us find the cure if we keep looking at cancer the same way we have been doing. The field of cancer research is in a crisis, and only if we change the way we view the disease we will be able to envision new and better strategies to fight it. \n
Avatar of: Alka Chandna

Alka Chandna

Posts: 3

November 20, 2008

Assuming that the war on cancer was intended to fight cancer in humans and not cancer in mice, we would suggest that the battleground for this war be shifted from hapless animals in laboratories to modern non-animal technologies. \n\nThe notion that animals in laboratories have very little predictive power in determining how human beings might respond to an experimental therapy is a consistent theme in the scientific literature and in assessments made by individuals who have been immersed in the war against cancer: \n\n? "The history of cancer research has been the history of curing cancer in the mouse. We have cured mice of cancer for decades and it simply didn?t work in human beings." ? Dr. Richard Klausner, former director of the National Cancer Institute \n? "For thirty-five years U.S. scientists laboring in the National Cancer Institute's screening program have injected more than 400,000 chemicals into leukemic mice hoping to find chemotherapies that would help solve the riddles of cancer... We've been using the wrong system as the screening device." - Dr. David Korn, Chairman of the National Cancer Institute Advisory Board\n? "Screening of over half a million compounds as anti-cancer agents on laboratory animals between 1970-85, only 80 compounds moved into clinical trials on humans. Of these only 24 had any anti-cancer activity and only 12 appeared to have a "substantial clinical role". But these so-called "new" active agents were not so new: they are analogues of chemotherapeutic agents already known to work in humans." ? Dr. Ronald Allison, Chairman of Radiation Oncology, Brody School of Medicine at East Carolina University\n? Experiments on animals intended to understand disease mechanisms have failed to translate to humans. A 2006 study published in the Journal of the American Medical Association concluded that, "Only about a third of highly cited animal research translated at the level of human randomized trials."\n? An article published in the August 3, 2006, issue of the New England Journal of Medicine noted that of all drugs that test safe and effective in animal tests, 94 percent are found to be either unsafe or ineffective in humans. \n? In the October 2005, issue of the British Medical Journal, Knight et al write: "The protracted time frames of animal carcinogenicity studies, and their substantial drain on human, financial, and animal resources, present other important disadvantages. Standard rodent bioassays take at least three years to plan, execute, and interpret. They have cost hundreds of millions of dollars and have consumed millions of skilled personnel hours. They also account for many of the animals reported to be experiencing the highest levels of pain and distress in laboratories." \n\nModern alternatives exist, such as 3-D in vitro models in which scientists grow actual human tumors surrounded by actual human tissue, allowing for controlled laboratory testing in an exact replica of in vivo human cancer. QSAR (quantitative structure-activity relationship) systems predict biological activity based on structure. Comparative studies of human populations allow doctors and scientists to discover the root causes of human diseases and disorders so that preventive action can be taken. Epidemiological studies led to the discoveries of the relationship between smoking and cancer and to the identification of heart disease risk factors. Microdosing is another promising alternative: Human subjects are given a drug dose that is one-hundredth of what would be expected to have an actual effect on the body, but sensitive measuring equipment is able to monitor the metabolism of the drug and allow scientists to predict the dangers or benefits of a full dose.\n\nInvesting in modern, non-animal technologies moves the war on cancer from the battleground from animals? bodies to systems that will yield human-relevant data, and with that, we may have a shot at winning the war. \n\n\n
Avatar of: Peter Sim

Peter Sim

Posts: 1

December 3, 2008

"Unlike the prevention of many other diseases, the prevention of cancer requires no government help, and no extra money."\n\nThat was written by Dr Otto Warburg.\nHe happened to acquire a Nobel Peace Prize in Medicine back in 1931. He had demonstrated that cancer cells do not thrive in the absence of glucose.\n\nHealthy cells cope vey well on ketones and fat.\n\nGlucose deprivation is not a wealth generating avenue for most of the usual suspects in cancer research funding.\n\nGlucose deprivation will not cure cancer, but it could postpone it until you die of something else (boredom?).\n\nThe absolute dependency of cancerous cells on glucose for survival ought to have alerted researchers on to possible lines of enquiry. I am surprised to find no follow up to Warburg's work.
Avatar of: anonymous poster

anonymous poster

Posts: 2

December 9, 2008

One of the most important steps in waging the war on cancer is to have the appropriate "soldiers". Unfortunately, there are far to many "generals", many of whom haven't spent enough time doing the actual science. There is far to much bureacracy, directors of directors, ad nauseum. Talking about curing cancer will not make it happen. With all apologies to those engineers out there, engineers will not cure cancer. It will take drugs and drug scientists to make that happen. Ever look at the background of those in charge? Too many people who make too many basic mistakes, all because they do not have the appropriate foundation of knowledge. Intelligent, yes, but there needs to be a more well-rounded leadership.
Avatar of: anonymous poster

anonymous poster

Posts: 1

December 15, 2008

Big team efforts work well on engineering projects, where the tools are available and the goals are clear. They do not work well in science, which is the exploration of the unknown. Most scientific experiments don't work -- but when designed properly are still informative. Organizing big projects -- which inevitably means relying on the judgement of one or a few people -- simply amplifies the consequences of negative experiments. I have been around long enough to remember the Special Virus Program at NCI in the 1970's where "everyone" knew that viruses caused cancer...and huge resources went into chasing that chimera.\nThere are of course defined goals within the scientific enterprise that benefit from big projects, such as the human genome sequencing. But in general there is no substitute for individual genius and dedication.

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