The RAS cancer switch – Can we turn it off?

March 25, 2022

Is there such a thing as a cancer switch? Faced with a new diagnosis of cancer, one often wonders how it developed , and if there was indeed such a thing as a cancer switch, how to turn that switch off?

 

 RAS ONCOGENE 

Yes Virginia, there is such a thing as a cancer switch, and the RAS protein is one of them. RAS stands for "Rat Associated Sarcoma virus protein" a very tiny cancer causing protein that was discovered in the rat sarcoma virus. In the normal cell, it is inactive but when this protein develops a defect or "mutation", it no longer controls regular cell division and now makes cancers very aggressive. ("Oncogene" means Onco-"Cancer" + gene. )

This is only one of the reasons why some cancers are so difficult to treat. And also why many cancers respond to regular chemotherapy for only awhile, only to relapse just a few months later.

 

CONTROLLING THE ENTRY OF SIGNALS

The RAS protein attaches to the inside of the cell membrane, and waits for signals coming to the cell surface from outside the cell.

Like a doorman sitting inside the entrance of the doors of a department store, the RAS protein waits by the door and decides whether to allow the signals coming through the door, into the rest of the store. Once they approve the visitor, they lead the signals into the inside of the store through a long pathway, until they reach the inner storeroom ( nucleus or brain of the cell ). There the nucleus makes more proteins, which eventually produce more new cells.

A BROKEN CANCER SWITCH

A CANCER IS BORN

When there are too many cells, the RAS protein decides to turn away new signals, in order to prevent overcrowding inside the store. It does this by deactivating itself by binding to a G protein called GDP which is a small portion of your DNA. When there is a defect in the RAS protein, it binds instead to GTP and it loses the ability to deactivate itself and as a result the doors to the cell remain perpetually open. In other words, it stays active. Signals keep coming, and the cell keeps sending these signals endlessly through the pathways into the the inner cell, and tumors are born. Cells cannot stop dividing.

This RAS protein is the cancer switch that now failed to switch off!

 

RAS cancer switch When attached to GTP, it turns on, causing cancer to grow, Attached to GDP, becomes inactive, and cancers stop growing.

 

Nowadays, every other flip of a magazine page brings me to an advertisement of the latest fashionable cancer drug boldy emblazoned in glossy print. Theses ads somehow are promising us that a cancer cure is finally on the horizon.

New biologic agents promise to target the tumor signaling pathways that encourage tumors to grow, divide and invade. Sounds like a winner eh? Chemotherapy to kill the cells and biologic agents to block the receptors and signals? But wait, there is one problem that needs to be addressed and that is the tumor "Switch". Even if you block one of the pathways, or even if you block one of the doors ( we call these doors tumor receptors) , cancer treatment can continue to be ineffective due to the presence of other doors and pathways.

There are also so many pathways, and if you happen to block the correct pathway, good. But if another pathway takes over, then the tumor will probably resurface.

 

FINDING A CURE

Is there a way to cover all the pathways? How about a drug to deactivate the cancer switch - RAS protein? A RAS blocking drug would be nice. Something to turn the cancer switch off.

Scientists are working overtime, trying to find out the correct combination of biologic drugs. Does it make sense to combine these new biologics with conventional chemotherapy in order to find a better cure?

Could a ketogenic diet (that helps tone down some of these tumor signaling pathways) be added to a RAS inhibitor drug? And could this plus chemotherapy (to kill tumor cells directly) be a winning anti cancer combination? The future is still bright and exciting things are in the horizon.

March 14, 2024
Breaking Down the Fear  Ketogenic diets often result in weight loss. Cancer patients frequently lose weight. Does this mean that keto diets are harmful to use in cancer patients? Cancer and weight loss are two topics that often come hand in hand, yet the relationship between them can be complex and sometimes frightening. Weight loss, particularly unexplained or rapid, can evoke fear in many individuals, often signaling underlying severe health concerns. However, when it comes to cancer, weight loss can sometimes be one of the earliest signs of the disease. In today's blog, we delve into the connection between cancer and weight loss, unraveling why the latter often instills fear and how understanding this relationship can lead to better health outcomes. Understanding Cancer and Weight Loss: Cancer involves uncontrolled cell growth and abnormal spread of cells throughout the body. These invading cells affect various organs and systems and disrupt their normal function. Weight loss can be very subtle or profound depending on the type of organ invaded. As cancer takes root and establishes itself, it also spews out cytokines (unique inflammatory proteins) that also serve as signal messengers, signaling muscles to lose volume, resulting in a weight loss phenomenon known as cachexia. Cachexia is a complex syndrome. Inflammation is often at the root of this problem, of profound muscle wasting, generalized fatigue, and poor appetite, Why Are We Afraid of Weight Loss? Weight loss, in general, is often perceived negatively in society. There's a prevailing notion that thinness equates to health, beauty, and success, while weight loss may imply illness or a lack of control. However, when weight loss occurs without intentional dieting or exercise, it can be a red flag for underlying health issues, including cancer. In cancer, especially, the presence of weight loss is disturbing because we traditionally associate it with illness. Association with Illness: Unexplained weight loss is commonly associated with illness, particularly severe conditions like cancer. The fear of the unknown and the potential implications of such weight loss can be daunting for individuals. To be of "normal" weight is equated with health. Loss of Control: Weight loss, especially rapid or involuntary, can make individuals feel like they've lost control over their bodies. This loss of power can be unsettling and exacerbate feelings of anxiety or fear. Uncertainty: Weight loss without a clear cause can be perplexing and raise questions about what might happen within the body. The uncertainty surrounding the underlying cause can contribute to fear and anxiety. During chemotherapy, however, weight loss is inevitable because we are in a catabolic state. The active cancer is making us lose weight. The key is to control or snuff out the underlying cancer. Once you weaken the tumor, less cytokine release and less inflammation will follow. As this occurs, the "source" of the cytokine release will die, and weight gain should naturally recover. Therefore, loading up on carbohydrates to make us appear to be of "normal weight" is incorrect. Loading up on sugary treats will only strengthen the cancer and will only be counterproductive! Conclusion: The fear of weight loss, particularly in the context of cancer, is understandable, given the potential implications for health and well-being. However, by understanding the complex relationship between cancer and weight loss and challenging societal stigmas, we can accept some form of healthy weight loss during chemotherapy. We can learn to recognize unhealthy weight loss (loss of muscle mass) and differentiate it from healthy weight loss during a ketogenic diet (most of which is weight loss from fat and excess water). As long as one feels energetic, with normal blood parameters and no indication of significant liver or kidney failure, anemia, or marrow failure, then some healthy weight loss during chemotherapy or implementation of a ketogenic diet CAN be acceptable.
March 4, 2024
Are you still drinking "ginger ale" during your chemotherapy sessions? You know, those gleaming, chilled cans of sparkly soda that your cheerful chemotherapy nurse hands out along with your anti nausea pills?  The scent and the taste of ginger help nausea stay away. But did you know that your "ginger ale" contains no ginger? Worse, the HFCS high fructose corn syrup, a highly processed sugar, can do you more harm than good. And making your cancer cells really happy. Next time you go for your chemo session, ask for water instead. Or better yet, bring your own ginger-infused drink from home. Here is some background about ginger. For centuries, ginger has been used as a remedy for nausea and digestive issues, and some scientific evidence supports its effectiveness. Here are some examples. Morning Sickness: Pregnant women often experience morning sickness, and ginger has been traditionally used to alleviate these symptoms. Several studies have shown that ginger can reduce nausea and vomiting during pregnancy. For example, a meta-analysis published in the Journal of Obstetrics and Gynaecology Research in 2014 concluded that ginger supplementation significantly reduced the severity of nausea and vomiting in pregnant women without any significant side effects. Motion Sickness: Ginger is effective in reducing motion sickness. A study published in Aviation, Space, and Environmental Medicine 1986 found that ginger was more effective than a placebo in reducing symptoms of motion sickness. Subsequent studies have supported these findings, suggesting ginger can alleviate symptoms like nausea, vomiting, and cold sweating associated with motion sickness. Chemotherapy-Induced Nausea: Cancer patients undergoing chemotherapy experience nausea and vomiting. The Journal of Alternative and Complementary Medicine 2009 published a review that analyzed several randomized controlled trials and found that ginger supplementation could reduce the severity of chemotherapy-induced nausea. Postoperative Nausea: Nausea and vomiting are common after surgery. A meta-analysis published in the journal Integrative Cancer Therapies in 2012 found that ginger effectively reduced postoperative nausea and vomiting compared to a placebo. However, we need more research to fully understand its mechanisms and best dosage. Everyone responds differently, but ginger, in its natural form, is usually safe to take during chemotherapy. Just make sure its the real thing! Photo credit Dan Sorum @ unsplash
January 30, 2023
Welcome to all our new members
May 17, 2022
Getting started on the keto diet usually sounds like someone is trying to lose weight? When you add cancer to that recipe, it becomes a whole new ball game. Do any of these thoughts sound familiar? “ I want to fight my cancer , and I heard that this diet can help me heal “ “ I’m confused because the keto diet will make me lose weight” “I’m afraid to lose more weight.” “I can’t afford to lose weight! “ “When is weight loss just right, and when is it too much? “ Is there real hope for me? Over the past two decades, I’ve seen my share of cancer patients. Yup, the whole package - diagnosis, anxiety, chemo, radiation, hair loss, weight loss, and, failures. But, I also saw many patients who achieve clean CT scans, remission, happy news, hair growth, and of course, the coveted weight gain. I have my own collection of patients with stage four cancers, a few have actually reached their ten to twelve year anniversary with me. Most of them have made it past five years and some are in complete remission. Yes, stage four to stage zero! How did they do it? You may have come to this website, searching for answers. I wish that I could tell you all that I know, in one sentence, but I can’t. It usually takes me several office visits to educate my patients. For now, you can stick around, and try to absorb the knowledge from current posts. Take time to read through my past blogs. Signup for a keto conference. There is one coming up very soon. The MHS 2022 in Santa Barbara California. May 5 to 8. Read books, and more books. You might be surprised. Not all books are the same. Some are full of dense material, while some are mostly fluff. But eventually, you will find the right book for you. Join me in one of my subgroups. But you need to fit the profile and be past the beginners stage when you join. Or you might get bored! I do show up there from time to time, to break the ice. And by the way, when you are stuck and can’t find the answers you are looking for...you need to make your voice heard and post your questions. What if my cancer doctor doesn’t approve? If your cancer doctor doesn’t know much about the keto lifestyle, or about metabolic approaches to cancer, don’t lose hope. Try to educate them, Share your knowledge. Even if they are at first resistant, with time, some will marvel at your progress and will notice that you are doing better than their average patients. Finally... the number one question that shows up on my blog.... What diet is best for me? I’m so CONFUSED! “ Dr. XXX on YouTube said that a keto diet and weight loss is good for cancer, but another doctor YYY said the opposite, that I should eat, healthy carbs, more plants, fruit , avoid fat and protein, try to gain weight. “ Dr. WWW advocates a vegan diet, but Dr ZZZ said do a carnivore diet.... , help!!!! Let me know your thoughts in the comments below!
March 30, 2022
There is exciting news on the horizon for glioblastoma, which is a deadly form of brain cancer. Have you heard of activated T cell therapy? It is similar to the car-T cell therapies that you often hear about for blood cancers. Well, this form of therapy is now available for patients with brain cancers. The catch is, you must enroll in a clinical trial. It is not yet available to the public. To qualify, one must have glioblastoma, a form of brain cancer , and cancer must have relapsed after the first diagnosis. Patients who are interested are now able to ask for information about enrolment at the Cedars Sinai Medical Centre in Los Angeles. This trial will be classified under a Phase one type of clinical trial. The drug company, Kairos pharma is the sponsor. This exciting new therapy, otherwise known as KROS 201, is a form of activated T cell therapy. The patient’s white blood cells are first harvested. Blood is removed by a simple intravenous blood draw, and then sent off to the lab to be processed in a cell culture. In the lab, the white blood cells are primed by exposing them to small protein substances called cytokines. This process will in turn activate the white blood cells, specifically the killer T cells. Once activated, these cells can now fight cancer by inactivating cancer stem cells. The T cells are returned to the patient’s body by intravenous infusion. The link for enrolment is not yet available but do keep checking on www.clinicaltrials.gov
March 25, 2022
Iscador, a type of mistletoe preparation was tested by a medical team in Israel alongside conventional chemotherapy in the treatment of patients with advanced non small cell lung cancer. Although no improvement in survival or quality of life was noted,non hematological side effects from the chemotherapy and hospitalizations were less in the group which received the mistle toe preparation. Possible yet unproven mechanisms of action include improvement of immune function via increasing the number of NK natural killer cells as well as improve the function of Tumor Necrosis Factor Alpha. Fever which is also a noted side effect of this preparation has been described prior to spontaneous regression of certain cancers such as melanoma implying a possible role of immunotherapy in the fight against cancer. No randomized trials on cancer patients have yet been published. 
March 25, 2022
We made little progress in the way of survival in the treatment of malignant brain tumors, specifically the deadly glioblastoma multiform. Despite aggressive surgery followed by radiation therapy and precautionary chemotherapy, they relapse early and survival is measured in months. Patients rarely survive beyond a year. Alternative therapies abound with few successes. Some patients attempt to enroll in clinical trials in search of new drugs that might make a difference in their survival.  There is a biologic treatment available. It is the monoclonal antibody called Bevacizumab. It supposedly controls the growth of blood vessels that supply nutrition to the brain tumor. Shrinking the blood supply supposedly starves the tumor. Very exciting, but nonetheless isn't a cure. Long term survivors still remain a rarity. There is mounting interest in metabolic basis of cancer development. In this respect, I do feel that ketogenic diets have potential benefit in brain cancer patients. The role of sugar and carbohydrates in the progression of brain tumors is interesting. Since most patients also are on steroids to improve brain swelling. It is also bad for them because this also increases their blood glucose. I wonder, if we are indeed adding fuel to the fire. A few case reports of brain tumor patients who were offered the ketogenic diet showed that some tumors stopped growing while others improved their survival. Notably, upon discontinuation of the diet, the tumor was noted to again progress, only to regain control upon reinitiation. Currently there are 4 clinical trials ongoing in the United States involving the ketogenic diet in the treatment of various forms of cancer. Another is ongoing in Germany. More clinical trial participation is desperately needed if we are going to move ahead and forge any progress with this deadly cancer. =
March 25, 2022
Three weeks ago I got word that another new chemotherapy drug has been approved for the treatment of colorectal cancer. Ideal candidates for this drug are patients who failed previous chemotherapy involving one of the following drugs: 5-Fluorouracil, Oxaliplatin, Irinotecan, Cetuximab (also known as Erbitux) and Avastin ( also known as Bevacizumab).This new drug has two active components, trifluridine and tipiracil. Trifluridine is a new nucleoside analog. In other words, a nucleoside is a nitrogen containing biologic compound linked to a sugar, which when phosphorylated, turns into a nucleotide, which is a vital part of the DNA backbone. Trifluridine therefore is a nucleoside analog, meaning it isn't but acts like a nucleoside. It incorporates itself into the DNA structure and interferes with cell growth and proliferation. Tipiracil inhibits the enzyme thymidine phosphorylase, which catalyzes the degradation of Trifluridine, thus allowing it to last longer. Thymidine phosphorylase by itself has pro-angiogenic properties, meaning it promotes blood vessel formation and encourages better blood supply of tumors, so Tipiracil directly stops this advantage. Furthermore, Tipiracil by stopping thymidine phosphorylase, prevents the formation of thymine and 2-deoxy-alpha-D-ribose 1-phosphate. 2DARP is a strong reducing sugar product of thymidine catabolism and causes increased oxidative stress within tumors, promotes release of more tumor blood vessel promoting factors ( angiogenic growth factors) such as interleukin-8, vascular endothelial growth factors VEGF, and matrix metalloproteinase-1 an enzyme which breaks down collagen and extracelular matrix, which is key in promoting tumor metastases. This three mode action of tipiracil ( inhibits thymine production, thymidine phosphorylase VEGF activity, stops ROS and MMP-1 , VEGF and cytokine production)- makes it more attractive since it can potentiate the action of the common colorectal chemotherapy drug 5- fluorouracil whose main action is to inhibit formation of thymine. The RECOURSE trial, a —international, randomized, double-blind, placebo-controlled study conducted in patients with previously treated metastatic colorectal cancer apparently resulted in statistically significant improvement in overall survival and progression free survival . The drug is given orally, twice a day, for two straight weeks, minus weekends, followed by a two week break. Side effects are listed as anemia, neutropenia, asthenia/fatigue, nausea, —thrombocytopenia, decreased appetite, diarrhea,vomiting, abdominal pain,—pyrexia. Since it is barely a month since FDA approval ( Sept. 24, 2015) it still has not hit our pharmacy shelves. I am however eager to try this. Will update you again in a few months. 
March 25, 2022
How long does it take to get into a state of clinical ketosis? By ketosis, I mean the levels of beta-hydroxybutyric acid reaching to above normal levels yet not high enough to bring you into a medical emergency such as ketoacidosis. As little as a day is all it takes. You an achieve this in different ways. The most common and sure fire method is to simply stop eating. If you fast and only limit your intake to water or sugarless herbal , which technically has ZERO calories, you will achieve a state of ketosis in no time. Another way is to try fasting for 15 hours a day, or roughly, just eat one full meal daily. this should bring you into ketosis too, though not all 24 hours are involved. If you try a ketogenic diet, that means, you will be limiting your carbohydrate intake to approximately 20% of your total daily intake, and take the rest in the form of fats ( 70-75%) and proteins (5 to 10%).  Monitoring your progress will be helpful. A simple glucometer will suffice. Individual serum Ketone sticks, readily available from Amazon.com or special order through your pharmacy can be used to check your ketone levels throughout the week.
March 25, 2022
Several clinical trials are ongoing throughout the United States at the moment.  The University of Iowa Department of Radiation Oncology is running a couple of Phase I trials on the use of the ketogenic diet plus radiation and chemotherapy in head and neck cancers, and they also have another which studies the ketogenic diet plus chemoradiation in non-small cell lung cancers and pancreatic cancer. Michigan State University has one which recruited brain cancers, also known as glioblastomas, a very deadly type of brain cancer. Duke University recently began a randomized trial studying the ketogenic diet plus androgen deprivation therapy in prostate cancer , using the ketogenic diet versus a control standard diet. Unfortunately per recent info posted on the clinicaltrials.gov website, the trial was terminated as of December 2015, due to lack of funding, and due to the principal investigator leaving . Closer to home, the Veterans Affairs Medical Center in Pittsburgh has their own trial which recently concluded in 2015. This trial recruited patients with advanced solid tumors across broad tumor types and patients dieted up to 16 weeks or until tolerated. The results have not yet been publicly released as it is currently under manuscript review.
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