Stopping the cancer signals

March 25, 2022

New cancer drugs are now available that target and stop the cell signaling pathways. Normal cells rely on chemical signals that tell them how to grow, divide, talk to each other, move around, and die.
Almost like a subway map, these are complicated, intertwined signals that cells use to communicate the instructions of life. When the instructions go wrong, chaos happens, and cancer cells take over in a very disorganized way.
 

Organized chaos in an NYC subway. Tumor signals look similar. Credit NYC subway map


Signals that train cells to change into a cancer

Signaling is a way of communication between cells, between cells and their central information hub, the nucleus, or between cells and their outside environment.
Cell signals can teach cells to grow, to divide, to start moving, or reproduce. Signals tell cells to stay organized and stick together in neat patterns. Cell signaling also tells the cell when to die (apoptosis). Cell signals can also cause damage. They can trigger inflammation, or tell cells to start moving to another location ( metastasize). Cell signals can also communicate with the immune system and make it attack invading cancer cells when they do show up in the body.
When cell signaling goes wrong, the cancers develop. Cancer begins from a baby cell or a stem cell. Cancer cell signals are uncontrolled, or erratic. The cancer cell loses the ability to die because the signals for death are destroyed.

Pro-cancer gene signals

Genes are characteristics that inherit from our parents. Pro-cancer genes ( also known as Oncogenes) are blueprints that eventually create a protein that is strong enough to transform normal baby cells (stem cells) into cancer stem cells. The RAS oncogene is one example of a pro-tumor gene.
The reverse gene is called a tumor suppressor gene. Both pro and anti-cancer genes can create signals that teach the cell to turn into cancer. Many new cancer drugs are available, and their purpose is to target a signaling pathway that hopefully, will cut the energy that fuels cancer.

Signals stop a tumor's blood supply (VEGF inhibitors)

Vascular ( blood vessel) - endothelial (blood vessel's inner wall)-growth factor- cancer cell signaling pathway. Anti-VEGF drugs are drugs that target signals that boost blood vessel growth. Anti VEGF drugs can cut the tumor's blood supply and indirectly make it stop growing. An example of new drugs that target the cancer blood vessels are anti-VEGF chemotherapy like Bevacizumab (brand name Avastin), which is a popular drug for advanced colon cancer. It attacks the VEGF pathway and cuts off the tumor blood supply, indirectly starving it.

Signals make cells grow, divide, move and die

We have a signal for everything that a cell does. A signal to make it wake up and divide, another signal to it to grow, meet other cells, and when the cell gets too old, there is a signal that makes it die. Cancer develops because the signaling pathways become defective, or overactive. The PI3K pathway meets up with another pathway, the AKT pathway, and another pathway, the mTOR pathway. Together they control how cells grow, move and die. PI3K, AKT mTOR are just shortcutted initials for a fancier, longer scientific name. Just remember they are all signaling pathways for cells, and they are intertwined. Drugs are being studied to possibly target these pathways.(Yang, Nie et al. 2019) Copanlisib and Duvelisib are examples of available anti PI3K / anti-cell signaling chemotherapies. 

How many cancer signals are there?

There is more than one. There are actually hundreds if not thousands of them, counting the ones we still don’t know about. It looks similar to the subway map. Tumor signaling pathways create changes in cancer proteins, in order to change their behavior to a less aggressive form. You will find it hard to convince me that a drug targeting a single signal, will cure your cancer. When the drug works, cancer will find a way to go around that roadblock. There is what we call "CROSSTALK" between cancer signals. It s easy to see why cancer will have no trouble finding a detour.

The cell membrane (on top) has receptors which process the signals and then transmits them through a complex maze, towards the center, where the cell will read the instructions and know what to do. Photo credit Qiagen

What triggers these pro-cancer signals?

There are many triggers. Metabolic stress, chemicals, radiation, carbohydrates, are all triggers for these cancer cell signaling pathways. Chemicals and radiation, heat, can cause cell damage from reactive oxygen species (ROS). Reactive oxygen species (ROS) are unstable molecules that contain oxygen and are highly reactive, causing damage to the center of our genes, the DNA, RNA and proteins. Our immune system can normally attack cancer cells and bacteria, when they do show up in our bodies. The immune system does this by releasing a vicious attack, and one of those defenders is the reactive oxygen species. However, if there is too much of this ROS, the stress builds up in the cell, and the cell becomes damaged. This is when OXIDATIVE stress occurs.

Our body defends itself against stress

Our body reacts by releasing enzymes that can melt away this stress from the reactive oxygen species. Some of these protective enzymes are called SOD (superoxide dismutase), and catalase. The words ends in "ase', usually means it is an enzyme. When our body is low on these enzymes, cell damage can happen. Pro cancer cell signaling is activated and cancers develop and grow. Food that are high in antioxidants can help blunt some of this damage.

Carbohydrates can trigger the PI3K/AKT cell signaling pathways

Veterinarians advice: Don't feed your dog human food, it will shorten their life! Photo by Christian Bowen on Unsplash


A study from Tehran found that high carbohydrate diets can help cancer cells survive by boosting the pro-tumor PI3K/AKT /mTOR cancer cell signaling pathway. Knowing that we now have drugs that target the PI3K and the mTOR pathways, it seems logical that a ketogenic diet might help multiply the anti-cancer effect of these targeted chemotherapies? Plant based food can tame overactive PI3K/AKT pathways, but adopting a ketogenic, low carbohydrate can be beneficial as well, since you can target not just one, but many cancer signals at once.
 
REFERENCES
https://www.clinicalnutritionjournal.com/article/S0261-5614(18)31888-0/fulltext
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968394/
Yang, J., J. Nie, X. Ma, Y. Wei, Y. Peng and X. Wei (2019). "Targeting PI3K in cancer: mechanisms and advances in clinical trials." Mol Cancer 18(1): 26.

Exploring the Link Between Cancer and Weight Loss:

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.

GINGER ALE DURING CHEMOTHERAPY

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

Welcome to all our new members

January 30, 2023
Welcome to all our new members

Getting Started On A Keto Diet

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!

New drug for relapsed Glioblastoma, a deadly form of brain cancer

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

Mistletoe plus chemotherapy in non small cell lung cancer

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. 

Brain cancer – Challenges with the ketogenic diet

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. =

Lonsurf, newly approved colon cancer drug

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. 

Getting into ketosis

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.

Update on clinical trials of the ketogenic diet in cancer

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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