An Introduction to Cancers
We believe that high quality clinical data are the gold standard. We contrast such data with the misinformation and myths that are commonly found in the tabloids, the often misguided policies emanating from the ill informed bureaucrats of the Healthcare system that cause unnecessary anxieties, and the well meaning but simplistic rhetoric employed by the charitable fund raising organizations. Our speciality is in presenting the hard data and allowing the readers to draw their own conclusions. For example, |
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People need facts, not myths, on which to make their choices. What follows below are data that may help that choice to be a more informed one. The Cancer QuagmireCancer research is a double-edged sword. On one edge are the practical issues faced by dedicated physicians and surgeons striving to improve the survival of their patients. On the other edge are the researchers, the tabloids and the charitable organizations, reporting daily on the discovery of yet another mutation which is claimed to cause cancer and yet another wonder drug which is claimed to cure cancer. Given that the survival times for the four major metastatic killers of breast, prostate, lung and colorectal cancers have barely increased in three decades, despite staggering amounts of funding for research, it is clear that there is a major disconnect between the clinic, the bench, the charitable organizations and the bureaucracies of the Health Care systems. The underlying reasons for this lack of progress have been fearlessly articulated by a small number of individuals, among them; Clifton Leaf, Executive Editor of Fortune magazine in New York; Michael Baum of London, one of the United Kingdoms most distinguished breast cancer surgeons with a 40 year track record in the National Health Service, and Harvey Bialy, a founding scientific editor of Nature Biotechnology, the worlds most respected scientific biotechnology magazine. Leaf’s hard hitting Fortune magazine article, Why we are losing the War on Cancer, documents the hundreds of billions of dollars of public and private money being spent on therapies for cancers with almost no perceptible progress in the key area of metastasis (2004, Fortune, 149, 76). |
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Read the article (PDF file 78,848 bytes) Given the above, where are the roadblocks to meaningful progress and how can they be overcome without continuing to pour further billions of dollars into a social, political and Health Care black hole that has become a mixture of spin and daily breakthroughs? The breakthroughs are so devalued that they currently represent little more than an infomercial for funding support. What is badly needed is genuine clinical progress, not fund raising in an atmosphere of heightened anxiety. People need facts, not myths in order to make decisions that are free of the scare mongering of the media and the ill informed agents of public health policy, (2000, The Breast Journal, 6, 331). Curing Cancer?The National Cancer Act was signed into law by Richard Nixon on the 23rd of December 1971 and it heralded the beginning of what was to be later called the War on Cancer. Since that time approximately $200 billion has been expended on this enterprise with little therapeutic benefit for patients with solid tumors, which after all make up 90% of all cancers. The often quoted exception is Gleevec, a drug which in some patients partially keeps in check a relatively rare liquid cancer, chronic myelogenous leukemia. However resistance to Gleevec develops rapidly and hence its description as a wonder drug is grossly overrated. However, there have been no equivalent successes for solid tumors, nor for metastatic cancers. The net result of over 30 years of work is summarized below for the four major metastatic killers and for metastatic ovarian cancer; these data being from the latest 2004 release of the US National Cancer Institute itself.
As has also been highlighted at the 2005 American Society of Clinical Oncology’s annual meeting in Orlando, Florida, metastatic melanoma survival hasn’t budged in 30 years (HealthDay, May 16th, 2005). Thus the five year relative survival for these cancer patients has remained essentially unchanged since 1973. Given these miniscule changes, something is very seriously wrong with the current research agenda. What are it’s failings and how can they be overcome so that the next 30 years is not a carbon copy of the last? Clinical RealitiesThe lack of progress in preventing or ameliorating the metastatic condition contrasts with the obsessive pursuit of mutation-based gene research, now elevated to a new level by the proposed $12 billion Human Cancer Genome Megaproject, (2005, The New York Times, March 28th, A1, and 2005, Nature Biotechnology, 23, 535). As Clifton Leaf has pointed out, the dysfunctional cancer culture pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs. The Megaproject is a perfect example of the shortage of good ideas. It ensures that mind-numbing activity will continue in the same DNA sequencing space, together with the detection and manipulation of mutations in cell lines and in the mouse, which is a largely irrelevant model for human metastatic cancer. Is it not astonishing that after three decades of gene-based mutational data with almost no clinical impact on the well being of the metastatic cancer patients themselves, that there is almost no thinking outside the box? At most medical centers, a different familiar theme is endlessly repeated; physicians do their best with resection and segmentectomy of solid tumors, multimodal toxic chemotherapeutic treatments, endocrine therapies and external beam radiotherapies. Depending on the time of diagnosis, the patients usually have a variable period of remission until the cancer returns, even for some CML patients treated with Gleevec. Drug resistance is the norm, not the exception. In the case of prostate cancer which kills over 40,000 individuals per year in the USA, and where more than 200,000 new individuals are diagnosed each year, the facts are that cancer treatments for solid tumors have not moved much beyond the surgical, radiation, and chemotherapeutic avenues that were developed decades ago. These clinical realities of mainstream cancer research have been documented by some distinguished members of the international medical profession. Judah Folkman MD, (2004, Nature 427, 787), highlighted the well known fact that most people carry dormant tumors that never progress to the metastatic condition. Thus almost all autopsied individuals between 50 and 70 have in situ carcinomas of the thyroid gland, but only 1 in 1000 of the individuals in this age group are diagnosed with thyroid cancer in this age group. Only 1% of women in the 40-50 age group are diagnosed with breast cancer, yet in excess of 30% of women in this age group are found to have in situ tumors of the breast at autopsy. In women diagnosed with ductal carcinoma-in-situ of the breast, 80% never become invasive even if left untreated (2000, The Breast Journal, 6, 331). Similarly, prostate cancer is often manifest in many different foci, only one of which may be invasive, (2000, Nature, 404, 921). Christoph Klein MD, of the University of Regensburg, has highlighted the important differences between the alterations found in primary breast tumors and those cells that have metastasized to other locations, (2003, Advances in Cancer Research, 89, 35; 2006, Klein and Holzel, Cell Cycle, 5, 1788). Contrary to popular belief, dissemination may occur early and metastases may seldom be derived from the dominant clone of the primary tumor but may arise from rare subclones. Whether these are from a stem cell-like subpopulation is not yet clear. However, such data are a wake-up call, reminding us that the cherished conventional linear model of cancer development is highly suspect. While hundreds of millions of women world-wide have first hand experience of the Pap smear test for the detection of cervical cancer, detection of prostate cancer in tens of millions of men routinely involves the Prostate Serum Antigen (PSA) test. Given the results, radical prostatectomy, external beam radiotherapy, hormone therapy to lower testosterone and competitive androgen receptor antagonists are then used to treat localized prostate cancer. However, it is now clear that the serum PSA test can be misleading in the diagnosis of prostate cancer and it has little to offer as regards the likelihood of metastasis. In a recent landmark article, Thomas Stamey MD of the Stanford University School of Medicine, examined the data from untreated radical prostatectomies over a 20 year period, (2004, Journal of Urology, 172, 1297). He concluded that serum PSA is only related to benign prostatic hyperplasia. Thus, The PSA era is over in the United States… and our study raises a very serious question of whether a man should even use the PSA test for prostate cancer screening any more. This is indeed a high octane clinical conclusion, not to be summarily dismissed. Finally, the reality for prostate cancer patients is that the therapies eventually fail and an androgen-independent, or hormone refractory condition prevails, resulting in a uniformly lethal drug-resistant stage, (2004, Nature Medicine, 10, 33-39). Research HypeIn stark contrast to the realities of the bedside, the operating theatre and the radiation rooms, is the impoverished rhetoric that flows from the mutational research bench. Tabloid and Internet headlines are generic and are routinely of the following type; Potential breakthrough in screening for ovarian cancer; Key to deadly form of skin cancer; Gene doubles breast cancer risk; Faulty gene fuels bladder cancer; Genetic link to thyroid cancer found; Genes for leukemia drug resistance identified; Tumor-starving protein identified; Protein may be key to prostate cancer, and Personalized cancer vaccine promises remission. This bombardment of yet another gene which causes cancer, yet another key to cancer, yet another target for cancer and yet another gene pattern specific for cancer reveal an insularity of thinking that is deadly. The community has trapped itself inside a mutational box from which it appears incapable of extracting itself.
While some predict that with the advent of cancer stem cells we have finally come to see the true face of the enemy, and that Cancer biology and treatment …. will become a science with a conceptual structure and logical coherence that rivals that of chemistry and physics, (2000, Cell, 100, 57). the bottom line is quite different. It is delusory to continue with the same research paradigm. What then is the nub of the outdated research paradigm that has failed so badly for 30 years? Why are there no signs of it’s imminent abandonment despite it’s lack of benefit for the survival of patients? |
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The following is an introduction for those who wish to learn more about cancer so that in discussions with their medical professionals, clinicians or researchers, they are able to make better choices about Healthcare issues. For further information see the Healthcare Community at 
Baum’s incisive overview in Prospect magazine, A new strategy for cancer, documents the clinical realities of cancer treatment where hugely expensive treatments yield only minor increments in survival. He points out that the War on Cancer is bogged down by undeclared special interests, petty-mindedness, political quick fixes and slavish adherence to outdated paradigms (2002, Prospect, 71, February 20th).
Bialys book, Oncogenes, Aneuploidy and AIDS: a scientific life and times of Peter H Duesberg, pulls no punches. It is a blistering expose of the mainstream cancer position. He painstakingly documents the pitfalls of the conventional mutational approach as compared to the implications of aneuploidogenesis in the context of networks and systems. (2004, North Atlantic Books, Berkeley, California).
Finally, a recent article in Nature Biotechnology has highlighted the serious flaws of the Human Cancer Genome Megaproject which aims to spend $12 billion dollars of largely taxpayers money on the mutational spectra of primary tumors, thus completely missing the overriding key issue in cancer, that of the metastatic spread of cells that will ultimately kill the patient.