Mark Rosenberg, MD: integrative cancer research and treatment.
Cancer (Care and treatment)
Cancer (Physiological aspects)
|Publication:||Name: Townsend Letter Publisher: The Townsend Letter Group Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 The Townsend Letter Group ISSN: 1940-5464|
|Issue:||Date: August-Sept, 2012 Source Issue: 349-350|
|Topic:||Event Code: 310 Science & research|
|Product:||Product Code: 8000220 Cancer & Cell R&D; 8000432 Cancer Therapy NAICS Code: 54171 Research and Development in the Physical, Engineering, and Life Sciences; 621 Ambulatory Health Care Services SIC Code: 8731 Commercial physical research; 8733 Noncommercial research organizations|
|Geographic:||Geographic Scope: United States Geographic Code: 1USA United States|
NEW DIRECTIONS IN CANCER RESEARCH
My current work focuses on research in cancer and aging. The cancer research is concentrated on metabolic approaches to treatment, applying therapies that interfere with the metabolism of cancer cells.
Cancer pH manipulation: lab studies. In 2007, I performed an initial study at Wake Forest University using a cocktail of drugs that was found to inhibit the ability of cancer cells to utilize glucose.
Two years ago, I performed a second study at the University of Miami on cancer glucose metabolism. In that research, I looked at two types of cancers, neuroblastoma and breast cancer, which both rely heavily on glucose. In fact, most types of cancer thrive on glucose and increase glucose uptake as they become more aggressive. The more aggressive the cancer cells, the faster the rate of glycolysis and the more lactic acid they produce. If the lactic acid is not expelled, the cells become so acidic they self-destruct. Seven different mechanisms have been identified through which cancer cells over-express the acid they produce.
For the first phase of this study, I selected two medications, drugs that are known to block two of the mechanisms responsible for pumping out lactic acid. I bathed the cancer cells in those drugs. Within 24 hours, 30% of the cancer cells died. That 30% cell death correlated with the accumulation of acid inside the malignant cells. I realized that if we blocked the efflux of acid from the cancer, the cells would succumb to their own acid production.
Taking this process a step further, I placed the remaining live cancer cells in a high-sugar medium, which included the two drugs blocking the efflux of acid. The hypothesis was that the more glucose the cancer cells consumed, the more acid they would produce. In 24 hours we saw 5O% cell death in those remaining cells, and once again, cell death correlated with an increasing accumulation of acid in the cancer cells.
Cancer pH manipulation: initial clinical results. Based on those findings, we began clinical trials overseas, working with cancer patients who had far-advanced stage IV cancers. Our goal was to determine to what degree this metabolic approach was effective in vivo, in the human body. From those trials, we confirmed that the therapy was nontoxic and gained invaluable information on dosage.
Once I had those results, I treated our first patient in the United States. M.N. had been diagnosed with metastatic endometrial carcinoma, stage IV. A debulking procedure had been performed to remove tumor tissue, but it was not possible to remove all of the tumor invading bowel and bladder. She was offered chemotherapy but declined. The oncologist indicated that she had perhaps a year to live and that she would probably become painfully symptomatic within six months. She decided to begin metabolic therapy. I developed a therapeutic cocktail that targeted four of the pumps that expel acid from cancer cells. After eight weeks, her tumor markers normalized, and she has been in complete remission from stage IV cancer for 21 months. That success generated a great deal of excitement, and I began treating other patients.
At that point, I was put in touch with a cancer researcher at Harvard, Dr. Vikas Sukhatme, MD, PhD, who told me that he had been lecturing on these same concepts for three years. He became a colleague with whom I began collaboration. In our research, we found that some patients had a tremendous response to this approach, but others did not respond. A third type of response was temporarily favorable and then the cancer would seem to find an escape path.
Cancers that thrive on amino acids. To carry this research further, I have been targeting protein scavenging cancers. It is well published in the literature that amino acids also feed cancer. Many cancers not only thrive on glucose from carbohydrates but become highly aggressive when excess glutamine, methionine, or phenylalanine are available. Glutamine, for example, can be used by cancer cells to directly create nucleosides that provide the basis for DNA.
This holds implications for clinicians. Many nutritionists and naturopaths replete cancer patients with glutamine to support immune function. However, it is important to bear in mind that numerous cancers are fueled by glutamine. Every cancer patient must be treated individually. The advanced-stage cancer patient's needs are highly specific, because completely different processes are in play.
A three-pronged approach to metabolic therapy. Our current strategy is to develop a comprehensive regimen in the metabolic treatment of cancer. In this approach, we block three of the metabolic pathways in the cancer cell: (1) the efflux of lactic acid, (2) glutamine use, and (3) the pentose phosphate pathway (an alternative to glycolysis).
Applying this protocol, we see patients on an ongoing basis and are collecting case reports in collaboration with Dr. Sukhatme from Harvard. The next step is a clinical trial. I believe that this cancer cocktail approach, like the HIV cocktail, is one of the most promising methods of cancer treatment today. I have developed a pharmaceutical company to design cancer cocktails that will be delivered by nanotechnology. The cocktail is placed in a nanoparticle and tagged so that it is only taken up by cancer cells. To date, we have completed the nanoparticle, costed out the particle, and demonstrated its financial viability. The next step is clinical trials in an animal model and then human clinical trials.
Normally, it can take up to seven years to obtain FDA approval for a drug. On the other hand, if a medication is approved as an "orphan drug" (one that treats rare conditions with fewer than 250,000 or 300,000 cases per year), the FDA will allow the drug to be fast-tracked within two to three years. The first condition we study will probably be pancreatic cancer or glioblastoma, because the prevalence of cases would qualify the medication as an "orphan drug."
CURRENT CLINICAL STRATEGIES
We look at cancer from a number of perspectives. The popular belief is that patients develop cancer because they are immune compromised. The reality is more complex. In aggressive forms of cancer, malignant cells send self-protective signals to the patient's white blood cells and bone marrow. This prompts white blood cells to secrete factors that support angiogenesis, enabling the cancer to create more blood vessels and continue to grow. In immunotherapy, our goal is to stimulate the immune system to destroy the cancer cells, through comprehensive treatment using a metabolic approach, immunology, and diet therapy.
Medications and supplements. The metabolic approach is our primary strategy, developed through the research described above. Current treatments include pharmaceutical medications used off-label and several supplements in high doses, such as vitamin D, curcumin, and resveratrol.
Hyperbaric oxygen. The role of oxygen, particularly hyperbaric oxygen, is underappreciated in cancer treatment. Historically, the work of Judah Folkman, MD, on angiogenesis implied that cancer could be destroyed by drugs which inhibit blood supply to cancer cells. We are now learning that decreasing blood supply actually makes cancers more aggressive.
As cancer cells become more hypoxic, a transcription factor described as hypoxia-inducible factor 1a is released, causing the cancer to become more glycolytic. The data show that the more hypoxic the tumor, the more aggressive.
Conversely, when we feed cancer cells oxygen, that reduces the aggressive nature of the cancer. In my experience, patients with cancer do better with therapies that increase the supply of oxygen to the tissues. Currently, a study is being conducted at Long Island Jewish Medical Center on the use of hyperbaric oxygen in cancer treatment.
Immunotherapy. Our approach to immunotherapy includes hyperthermia, medications, and botanicals:
* Hyperthermia--We employ whole-body hyperthermia. As the cancer cells become more acidic, they also become more susceptible to heat therapy.
* Naltrexone--We also utilize low-dose naltrexone, an opioid antagonist, to increase the body's production of endorphins and enkephalins. Met-enkephalin, or opioid growth factor, is particularly effective in inhibiting cancer growth.
* Mistletoe--In some cases, treatment includes injections of mistletoe, which we import from Germany. This provides a mild stimulant to the immune system and increases activation of natural killer cells and mature T-cells.
* Other botanical supplements--We frequently prescribe supplements such as astragalus to improve immune function.
Ketogenic diet. Frequently patients are told, "It doesn't matter what you eat if you have cancer. Just don't get too thin." In fact, the data shows that cancer thrives on glucose, so carbohydrates are not a good choice of nutrition.
In our practice, patients with glycolytic tumors are prescribed a ketogenic diet (not to be confused with an Atkins diet). To limit carbohydrates and glycolysis, the ketogenic diet consists of 10% to 15% carbohydrates and 5% to 10% protein. The patient consumes protein in such limited amounts that it cannot be converted to carbohydrates. Calories are provided by an intake of 75% to 80% healthy fats, typically medium chain triglycerides such as coconut oil and palm kernel oil. Normal cells are forced to metabolize these fatty acids into ketones. Although the brain and the body can utilize ketones, most cancers have difficulty metabolizing ketones. We combine this dietary approach with other techniques in an inclusive protocol.
No single therapy is currently effective against all forms of cancer. The most promising forms of treatment are metabolic therapies that manipulate the biochemistry of cancer cells to control the disease. In my experience, a comprehensive approach that includes metabolic treatment is usually the most successful.
MARK ROSENBERG, MD
Dr. Rosenberg received his medical degree from Georgetown University School of Medicine and serves as director of the Fellowship in Integrative Cancer Therapy with the American Academy of Antiaging Medicine, the first and only fellowship of its kind in the United States. His clinical practice in antiaging medicine is located in Boca Raton at the Institute for Healthy Aging. He is chief medical Officer for LifeLength, which provides lab testing on telomere health as a marker of aging; and chief science director of Research and Development for Vitalmax Vitamins.
Dr. Rosenberg has been involved in the research and development of pharmaceuticals since 1991. In 2001, he developed and patented a drug to aid in the management of obesity and diabetes, and he also has a patent pending for an oral appetite suppressant. He is currently researching novel compounds to treat cancer and has received approval status for a new investigational drug that works in conjunction with chemotherapy.
The Institute for Healthy Aging
The Institute for Healthy Aging
4800 North Federal Highway
Boca Raton, Florida 33431
American Academy of Anti-Aging Medicine
Topics covered in-depth in the 11 fellowship modules include the following: the molecular biology of cancer; genetic and viral predispositions; tumor profiling, individualized chemotherapy, antioxidant therapy, leading-edge radiation therapy, chemotherapy (old and new drugs), stem-cell transplantation, and off-label pharmaceuticals in cancer treatment; immunosuppression, immunodeficiency, immunotoxins, and interferon therapy; assessment and treatment of therapy-induced conditions; promising emerging treatment including avemar therapy, cancer pH manipulation therapy, Coley's toxins, Hoxsey therapy, hyperbaric oxygen therapy, hyperthermia, photodynamic treatment, protocell therapy, and sonodynamic therapy; dietary interventions; and herbal supplementation. Treatment and patient care are presented in the context of the management of an integrative cancer practice.
1801 N. Military Trail, Suite 200
Boca Raton, Florida 33431
Toll-free phone: 888-997-0112
International phone: 561-997-0112
an interview with Nancy Faass, MSW, MPH
Nancy Faass, MSW, MPH, is a writer and editor in San Francisco who has worked on more than 40 books for publishers that include Elsevier, Harper, McGraw-Hill, Mosby, New Harbinger, New World Library, North Atlantic, and others. Director of The Writers' Group, she also provides articles, white papers, and writing for the Web. For more information, see www.HealthWritersGroup.com.
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