Current Controversies

by Ira L. Goodman, MD, FACS, ABIHM, FAARM

Early Cancer Detection: Good, Bad, or Irrelevant?

The subject of early cancer detection is one of great interest. Most people think that if cancer is diagnosed early enough, it is curable or at least more easily controlled. This is based on the prevailing narrative that cancer starts in one cell and then multiplies according to its own “doubling time” schedule. The narrative also claims that the nuclear DNA is what causes this wild growth. Both of these premises are being challenged by research in several centers. The fact that nuclear mutations are so variable even within the same tumor and the abysmal failure of drugs that target DNA mutations both encourage a reevaluation of the prevailing paradigm. As Ayn Rand famously said over and over: “Question your premises.” Clearly we are on the wrong path in the War on Cancer, given the dismal statistics for the overwhelming majority of solid tumors, which are no better than 50 years ago.

There are several new and promising lab tests that claim to detect cancer many years before it is evident on traditional scans. In this column I will attempt to describe and then comment on some of these new tests, as well as the clinical relevance that they may or may not have.

The first test I will describe is the ONCOblot test discovered by the Morrés from Indiana. This expensive test ($850) claims to isolate the ENOX2 protein from serum at a very early stage (a few cells) and even further claims to be able to determine the tissue of origin. They have also developed a unique compound (green tea extract plus capsaicin ) which, if taken every 4 hours around the clock for about 6 months, can reverse the abnormal ENOX2 marker. Is this the holy grail? Too early to tell, since only about 1000 of these tests have been done to date; but if it does what they claim it does, then cancer will be a disease of the past, assuming that you can convince millions of people to take this test and the treatment decades before they are symptomatic and repeatedly monitor themselves throughout life. This has little chance of happening in a widespread manner but still it is enticing. If there is a clinically evident cancer already diagnosed by conventional means, then this test may be of some benefit in measuring progression. However, I believe that its main appeal is as a screening test, if it works. What does a patient do if the test comes back positive but there are no signs of cancer – undergo extensive diagnostic testing which will probably yield nothing? Worry? Take the compound which reverses the positive test result and wonder if it really is reversing an incipient cancer or just reversing the lab marker? Many real questions have yet to be resolved. Right now, I think that this test is confirmatory only and not ready for prime time. That may change, however.

Treating a lab test is never as important as treating the disease itself, and the premise behind this test is that the ENOX2 protein means that a clinically significant cancer is developing and will manifest itself. This has yet to be proved.

Another early detection marker getting a lot of press is the CTC and sensitivity testing done by the RGCC (Research Genetic Cancer Centre) lab in Greece. This test (which can cost thousands of dollars depending on which version you order) claims to isolate circulating tumor cells from peripheral blood and then expands these cells to determine chemosensitivity to a variety of pharmaceutical and nutraceutical agents. If a patient already has a known cancer, this may point you in the right direction. If no cancer is diagnosed, however, using it as a screening method is dicey. Again, what do you do if it’s positive? Probably the same thing that anyone should do without the test – optimize diet, lifestyle, supplements, immune competence. In an undiagnosed patient, it serves as motivation to do these things more than anything else, as long as the patient does not get too stressed out about a positive result, which of course can encourage cancer growth. None of this has anything to do with prevention. Early detection is just that – early detection. It is not prevention. There are some cancer patients who could benefit by early detection; but in others, it can be harmful by leading to damaging treatments. On balance, the latter scenario is more common.

Other screening tests such as the Cologuard stool DNA test for colon cancer; the HCG test in its various forms; the PHI (phosphohexose isomerase enzyme, which goes up with anaerobic metabolism that is common in cancers); the TK1 (thymidine kinase test, which becomes elevated in some cancers); the nagalase test (which can be treated with GcMAF); the Biofocus test from Germany, which claims to do the same thing as the RGCC test; CRP and other inflammatory markers; the liquid biopsy test from Pathway Genomics (claims to measure tumor DNA of some cancers circulating in the blood); as well as other tests that claim to diagnose cancer decades before clinical presentation.

We have all heard the current mantra of cancer progression staring with one cell, doubling at a variable rate, and progressing over years or even decades until it reaches the stage where it is clinically evident. The doubling time varies with the degree of cell differentiation, as well as the immune competence of the individual. The obvious conclusion from this theory is that the elimination of the first aberrant cell (or the first few) will eliminate all the downstream problems with cancer and that any test that can detect a small number of cells is a major advance. Most of the research dollars and certainly the overwhelming majority of conventional oncologists believe in this theory as well as the corollary that the nuclear DNA is responsible for these abnormal divisions. Hence the frantic multibillion-dollar search for targeted drugs against DNA mutations. However, the results have been an abysmal failure, as can be seen from the statistics on both cancer deaths and incidence rates over the last 50 to 60 years. With rare exceptions (Gleevec), this approach does not work. Could the paradigm be wrong? I say yes. There are researchers who agree and propose a multifocal origin of most cancers primarily resulting from mitochondrial dysfunction based on a low-oxygen environment. In other words, cancer is a metabolic disease of widespread nature which manifests in a variable fashion. Otto Warburg first proposed this common pathway but Seyfried, D’Agustino, Pedersen, Ko, and others are doing active research along these lines, which is compelling. Their nuclear transfer experiments seem to prove their point, as does the variability in nuclear DNA mutation types within an individual tumor, between the primary tumor and their metastatic lesions, and between different patients with the same kind of cancer. Something more basic is going on, and it appears to me that it’s the mitochondrial dysfunction as well as it consequent preference for anaerobic metabolism that causes downstream variable mutations in the nuclear DNA. That is, the DNA mutations are a secondary result of the primary process of mitochondrial dysfunction rather than the primary cause of cancer, as is widely believed. Unless this primary cause is addressed, all the early diagnosis in the world will not prevent future malignant transformations in the patient. That combined with early spontaneous malignant cell regression in many cancer patients makes the entire idea of early detection tests of doubtful significance. Gilbert Welsh has written a great deal on this subject, and his books are worth reading. There are many cancers which are overtreated and overdiagnosed (prostate cancer and breast cancer are good examples for this industry), but there are others. Obviously, there are cancers that need to be treated, some of them aggressively. The various methods of treatment, both conventional and otherwise, are beyond the scope of this column. Early diagnosis is great for the tumors destined to grow rapidly, but unfortunately we do not know which ones these are in most cases, and the unrelenting search for all cancers (dangerous or not) has led to much morbidity, fear, and death. Sometimes if you feel all right, you really are all right. Most of the time, you should not go looking for trouble, since you will eventually find it. Let it find you and focus on a healthful lifestyle instead. Just my opinion.