Cancer: Past, Present, and Future. Sheldon Cohen M.D. FACP

for early disease detection and prevention. The “Big Data” was in the process of analysis.

      The USPSTF’s decisions impacted not only patients, but physicians, insurance companies, and laboratories, resulting in usually prompt angry protests from these disparate groups especially as financial considerations enter the picture and as cost-effectiveness rears its ugly but crucial head. Examples:

      1.In 2009 it made a recommendation to abandon the yearly mammogram requirement for most women between the ages of 40 to 50, but rather start at age 50. This was based upon the unfavorable benefit to risk ratio of doing this test in the 40 to 50 age group: the large number of false positive mammography’s and the negative consequences of doing unnecessary procedures based upon false positive results.

      2.It also recommended eliminating the yearly PSA test for prostate cancer for men ages 40 to 54. This too emanated from the fact that false positive PSA’s and the necessary biopsies resulting from same in this age group were causing significant morbidity. Men from 55 to 69 years of age may have the test done if the doctor and patient agree. Men over age 70 or any man with less than a 10 to 15 year life expectancy could forgo the PSA test.

      3.Screening tests for colon cancer, including stool blood tests, sigmoidoscopy or colonoscopy are recommended all at intervals agreed upon by the physician and patient based upon clinical facts.

      4.There are no decisions currently about any definite effective lung cancer screening tests.

      5.There is no definite determination whether whole body skin examinations for melanoma are beneficial or harmful.

      This is all part of the big-data revolution taking place in healthcare today: data from clinical trials, years of research from pharmaceutical companies, insurance data on patients with various diseases, information from payers, hospital data, laboratory data, physician practice data, all congregated and studied with the goal in mind to streamline healthcare from the medical standpoint as to what is best for patients, and from the financial standpoint as the cost of healthcare, which if left unattended, may well break the bank. And this latter pressure is the main factor driving this demand for medical and fiscal responsibility.

      Now if all patients would just play a role in their own health by not smoking, not drinking alcohol, exercising regularly, follow preventive measures, and eat with optimal health in mind, our medical and financial healthcare crisis would be moderated to the point where much of our worries and financial and medical pressures would minimize. And what a boon that would be!

      CHAPTER 4

      Cancer without disease

      Medicine, to produce health, has to examine disease; and music, to create harmony,

      must investigate discord

      Plutarch

      A.D. 46-120

      We all get cancers on a daily basis, and we get them often. They arise in all parts of our bodies, grow to approximately one to two cubic millimeters, consist of thousands to millions of cells and remain dormant; they do not metastasize (spread to other parts of our bodies), they stay in place, growth inhibited, are harmless in this stage, and are known as in situ cancer, or cancer without disease. Why don’t they grow and spread like cancers are supposed to do? The cells of these “cancers” only grow and divide to a certain level and when they reach a point where their tumor mass exceeds their blood and oxygen supply, growth and cell division ceases. To understand the reason for this growth inhibition requires an understanding of angiogenesis (angio…blood vessels; genesis…growth).

      Angiogenesis is a vigorous process during fetal growth in utero. A developing fetus cannot develop without blood vessels, so growth of these blood vessels is vigorous and extensive. Not so after full fetal development when the only time there is blood vessel growth is during pregnancy (growth of placenta), during active repair of injuries, and the process of menstruation when the uterine lining grows new blood vessels every month.

      But all cells, including cancer cells, want to grow and develop and they do what they can to activate the process of angiogenesis; the production of new blood vessels to feed the dormant tumor of the necessary blood and oxygen to grow and expand beyond the one to two cubic mm growth limit nature has set on the cluster of dormant cancer cells. How do they do this? Researchers discovered that these dormant cancer cells release proteins capable of activating the process of angiogenesis. At least a dozen different protein molecules have been identified as being angiogenic (can trigger new vessel growth). The two main ones are: vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF). In addition, to these stimulating vascular growth factors, cancer cells also liberate vascular inhibiting growth factors setting up a battle between vascular growth and vascular inhibition, mostly creating a neutral stalemate where the early cancers do not grow and spread, remaining at their one to two cubic millimeter stable, non-growing level.

      The pioneer in this work was Judah Folkman who developed this thesis in 1971.

      As long as the proangiogenic factors and antiangiogenic factors balance, there will be no growth, but if proangiogenic factors are able to predominate, cancer growth (and even benign tumor growth) will be able to “take off.”

      It took until the late 1980’s for the scientific community to embrace Folkman’s concepts that cancer growth and spread depended upon angiogenesis. To this point, treatment of cancer focused on killing or eliminating cancer cells. And it still does: eliminating them by surgical approaches; killing them by radiation or chemotherapy. Angiogenesis slowly evolved into an approach not focusing on the cancer cell itself, but rather focusing on a factor that “fed” the cancer, in essence starving it to death. By 2004, the Food and drug Administration approved 10 drugs that inhibit angiogenesis, used not only against cancer, but also against some benign diseases such as age-related macular degeneration where angiogenesis also takes place. Progress is slow and ongoing, but the magic bullet hoped for in the angiogenic inhibiting therapeutic approach is not the hoped for cure.