The sun rises and the sun sets. It seems like the sun rotates around the Earth. Cancer cells rise and are killed by surgery, radiation and chemotherapy. It seems like cancer is a disease. But the sun does not rotate around the Earth, and cancer is not a disease. The many forms kinds of cancer cells are the products of the disease neoplasia that can emerge in almost all of our bodies’ organs and tissues.
Strange as it may seem, much of the failure of the War on Cancer─and more importantly, much of the potential for finally winning it─has to do with the definition of cancer.
In a 2013, Time magazine article, Bill Saporito described cancer as “not just one disease; it’s hundreds, potentially thousands. And not all cancers are caused by just one agent—a virus or bacterium that can be flushed and crushed. Cancer is an intricate and potentially lethal collaboration of genes gone awry, of growth inhibitors gone missing, of hormones and epigenomes changing and rogue cells breaking free. It works as one great armed force, attacking by the equivalent of air and land and sea and stealth, and we think we’re going to take it out with what? A lab-coated sniper?” This image of cancer as a myriad of diseases makes cancer seem unconquerable.
In contrast, if we think of cancer as a complicated array of conditions arising from the same dysfunctional bodily process of neoplasia, it makes it easier to organize research and treatment around preventing and stopping that process. The journal Neoplasia does this by encompassing the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Cancer remains a daunting challenge, but at least we have conceptual clarity now to guide us rather than overwhelming confusion.
To simplify the matter, killing cancer cells is like using insulin to lower the blood sugar levels in diabetes. Both cancer cells and high blood sugar are products of underlying diseases: cancer cells of neoplasia and high blood sugar of deficient insulin production by the Isles of Langerhans cells of the pancreas in type 1 diabetes. Incidentally, scientists at the University of North Carolina School of Medicine and the City of Hope National Medical Center are opening the door to treating the cause of diabetes by showing that injections of certain antibodies reinvigorated the Isle of Langerhans cells and reversed the onset of Type I diabetes in mice genetically bred to develop the disease. Moreover, just two injections in the North Carolina study maintained disease remission indefinitely without harming the immune system.
Although proposed in 1957 and subsequent decades, only recently has the focus of cancer research been shifting to why there is a lapse in our bodies’ natural defenses in our immune systems that ordinarily detect and destroy abnormal cells. That lapse permits cancer cells to grow and spread.
The major focus of cancer treatment has been on “search for and destroy cancer cells.” It has been on destroying cancer cells…not on preventing or stopping their formation. Tumors are identified and surgery, radiation and/or chemotherapy are used to eliminate cancer cells. In the process, especially with radiation and chemotherapy, normal growing cells are destroyed as well, and the body’s natural defense system—the immune system—is compromised. This model relies upon the fallacy that medical interventions can cure a disease without the help of our bodies' natural defenses. Most importantly, it focuses on the products of a disease─cancer cells─rather than on the disease itself…neoplasia.
A more realistic and productive model is based on the fact that our normal body cells are continuously changing and, if in that process they do not die normally, can mutate through a process called neoplasia and become cancer cells.
Some 2,400 years ago the Greek physician Hippocrates described cancer as spreading out and grabbing on to another part of the body like "the arms of a crab," as he elegantly put it. Similarly, a popular view is that cancer begins when the cells of an expanding tumor push through the thin membrane that separates them from other tissues. It's a fancy way of saying that in order to become cancer, a cell has to go beyond its normal boundaries.
"Absolute nonsense!" said Michael Sporn, a professor of pharmacology and medicine at Dartmouth Medical School. He went on: "We've been stuck with this definition of what cancer is from 1890. It's what I was taught in medical school: 'It's not cancer until there's invasion.' That's like saying the barn isn't on fire until there are bright red flames coming out of the roof."
In fact, cancer begins much earlier than that. And therein lies the best strategy to contain it. Sporn advocates preventing cells from entering the deadly stage of becoming cancer cells in the first place. He has been struggling for many years to get fellow researchers to start thinking about cancer not as a thing but as a process, called carcinogenesis─neoplasia, a multistage process that goes through various cell transformations and that can progress slowly or rapidly.
So intervention must occur earlier in the process of neoplasia. To do this, the medical community has to break away from the notion that people in an early stage of neoplasia are "healthy" and therefore shouldn't be treated. People are not healthy if they're on a path toward cancer.
If this seems radical and far-fetched, consider this. We've prevented millions of heart attacks and strokes by using the very same strategy. Sporn likes to point out that heart disease doesn't start with the heart attack; it starts way earlier with dietary factors and insulin that cause arterial plaque (hardening of the arteries). So we treat those. In the same way, a stroke doesn't start with a blood clot in the brain. It often starts with hypertension. So we treat that with both lifestyle changes and drugs. "Cardiovascular disease, of course, is nowhere near as complex as cancer is," he admits, "but the principle is the same." Sporn adds: "All these people who are obsessed with cures for cancer are being selfish by ignoring what could be done in terms of prevention."
Actually, this principle is being applied to a limited extent right now. A perfect example is the Pap smear, which detects precancerous changes in the cells of the cervix. That simple procedure, followed by the surgical removal of any lesions, has dropped the incidence and death rates from cervical cancer by 78% and 79%, respectively since the practice began in the 1950s. Over 170 million tests have been given worldwide. In countries where Pap smears aren't done, cervical cancer is a leading killer of women.
The same goes for colon cancer. Not every polyp (a growth in the colon's lining) goes on to become malignant and invasive. But colon cancers have to go through this abnormal step on their way to becoming deadly. The list of other pre-cancerous conditions goes on from Barrett's esophagus (a precursor to cancer there) to hyperkeratosis (precursor of skin cancer). Doctors already are doing this kind of prevention with some other cancers, but they need to do it much more.
Biomarkers of Neoplasia
Some complain that the telltale biomarkers of neoplasia, while getting more predictive, still are far from definitive, and that we should wait until we know more. Researchers in heart disease, meanwhile, have taken the opposite tack and been far more successful. Neither obesity nor hypertension guarantee future cardiovascular disease, but they're treated anyway.
A few cancer researchers have made great strides in finding early warning signs by looking for protein and DNA breakdown products─"neoplastic signatures"─in blood, urine or even skin swabs that can identify precancerous conditions and very early cancers that are likely to progress. For instance, Lance Liotta, former chief of pathology at the National Cancer Institute, has demonstrated that ovarian cancer can be detected by a high-tech blood test—one that identifies a unique "cluster pattern" of some 70 different proteins in a woman's blood. "We've discovered a previously unknown ocean of markers," he said. “And it's potentially a mammoth lifesaver. With current drugs, early-stage ovarian cancer is more than 90% curable; late stage is 75% deadly. Early results on a protein test for pancreatic cancer are promising as well,” said Liotta.
One test is available now that could be useful with most cancers. Blood DNA levels have been found to be significantly elevated in patients with esophageal cancer and to return to normal levels following complete surgical removal of the cancer. Persistently elevated blood DNA levels after surgery or levels that rise on follow-up indicate residual or recurrent cancer. Since DNA damage is a characteristic of neoplasia, this test may have broad applications.
Yes, the strategy has costs. Some say wholesale testing of biomarkers and early lesions─many of which won't go on to become invasive cancers─would result in a huge burden for the healthcare system and lead to a wave of potentially dangerous surgeries to remove things that might never become lethal anyway. But the costs of not acting are much greater.
Models for Treatment Directed at Cancer Cells Themselves
Focusing on neoplasia alone is not sufficient for destroying cancer cells that already have gone through that process. For a patient to become “cancer free” anti-cancer agents must 1) eradicate the primary tumor, 2) eradicate any tumors at other body locations that have arisen via metastasis and 3) eradicate any circulating tumor cells that remain in the blood. One such agent that holds promise for doing all three is 3-bromopyruvate (3BP) discovered in Dr. Peter Pedersen’s laboratory at Johns Hopkins University by Dr. Young Ko near the turn of the century. Like a “Trojan horse” 3-BP enters the cells of animal cancer tumors, targets HK-2 and quickly dissipates their energy production factories (glycolysis and mitochondria) resulting in tumor destruction without harm to the animals. In addition, 3BP at a dosage that kills cancer cells has little or no effect on normal cells. Therefore, 3BP can be considered a member of a new class of anti-cancer agents that attack the metabolism of cancer cells forming through neoplasia.
Researchers at the Mayo Clinic in Florida have identified a number of agents—some already used in the clinic for different disorders—that may force shape-shifting in tumor cells to immobilize them and thus prevent metastasis.8 The researchers found that a protein called Syx is key to determining how tumor cells migrate. When researchers removed Syx from the cancer cells, they lost their polarity—their leading and trailing edges—and morphed into a “fried egg” shape.
Investigate All Significant Leads
There is good reason to question claims of successful cancer treatment that fall outside of the established professional fields. Quackery thrives when people are desperate to find effective treatment for all diseases. At the same time there are many reasonable leads that might prove productive, such as nutritional therapies, which are employed in Europe and in the United States, and scorpion venom therapy, which is used in Latin America.
Strikingly, nutritional therapy for cancer has not been subjected to clinical studies in the way that chemotherapies have. This is most unfortunate since patients have been deprived of nutritional adjustments that could be helpful to them or of solid advice regarding their lack of effectiveness.
An example of a specific agent that may be a harbinger of things to come in destroying cancer cells that have formed tumors is blue scorpion venom. This venom is widely used in Cuba and other South American countries to treat cancer. Cuba's state pharmaceutical company, Labiofam, produces a homeopathic version of scorpion venom called Vidatox, which may not be as effective as normal doses of the venom that have been used. A handful of countries have registered it for sale, but it has not been evaluated in peer-reviewed journals. According to authoritative reviews by U.S. physicians, the Cuban health system merits attention as an example of a nationally integrated approach resulting in improved health status. We should not need an elaborate clinical trial to give an indication of whether or not this venom works in the United States. One reputable oncologist could use it with ten patients as a preliminary trial.
Scorpion venom actually has been used in the United States for brain tumors in the form of a tumor paint that is a molecule derived from the venom consisting of two parts. One is a chlorotoxin, a protein that can attach itself to chloride channels on a cancer cell surface. The other is a dye that fluoresces when you shine a light on it. So if you inject the paint into a cancer patient's bloodstream, it will attach itself to the tumor. This means the tumor can be made to glow during surgery, making it easier for the surgeon to find and remove. It also makes less invasive surgery possible.
A Paradigm Shift Is Needed
A paradigm shift in the cancer field is needed based upon two fundamental principles of medical practice: 1) do no harm (chemotherapy destroys normal cells and suppresses the immune system with debilitating side effects) and 2) base research and treatment on diseases not on their symptoms or signs. Cancer cells are signs of an underlying disease: neoplasia. The variety of factors in cells and their microenvironments that induce and that fail to block neoplasia in organ systems and tissues should be the focus of research and treatment. Immunotherapy is devoted to addressing these factors.
The commonly accepted definition of cancer is responsible for much of the failure of the War on Cancer. We have been intervening after the horse has left the barn.
Words we use determine our perceptions and our actions. So simply fighting cancer by killing cancer cells is not enough and is gravely misleading. If the War on Cancer organized in the late 1930s had become a War on Neoplasia when the latter was clearly identified as the process that produces cancer cells in the 1970s and 1980s, we may well have had effective treatments for the many forms of cancer today.
Changing the Way We Think About Cancer
The evolution of new approaches to cancer is outlined. They are both reactivating
long known theories and treatments and trying out new ideas and methods.
Chapter 1 - Our Journey with Cancer
Chapter 2 - Conventional Cancer Treatment
Chapter 3 - Navigating the Cancer Care System
Chapter 4 - Background for Understanding Cancer
Chapter 5 - How Cancer Cells Form and Multiply
Chapter 6 - Cancer Research
Chapter 7 - Testing Treatments
Chapter 8 - Changing the Way We Think About Cancer
Chapter 9 - Immunotherapy: Drawing upon Your Body’s Resources
Chapter 10 -Nutritional Therapy: Drawing on Nature’s Resources
Chapter 11 - What You Can Do Now to Complement Your Cancer Treatment
Chapter 12 - Taking Charge of Being a Care Recipient or Caregiver
Chapter 13 - Where Are We Now?
Chapter 14 - Obstacles to Progress
Chapter 15 - Where Do We Go from Here?
Chapter 16 - How Can We Win the War on Cancer?