Newswise — ST. LOUIS — In research published inCancer Cell, Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University, has, for the first time, found a way to stop cancer cell growth by targeting the Warburg Effect, a trait of cancer cell metabolism that scientists have been eager to exploit. Unlike recent advances in personalized medicine that focus on specific genetic mutations associated with different types of cancer, this research targets a broad principle that applies to almost every kind of cancer: its energy source. The Saint Louis University study, which was conducted in animal models and in human tumor cells in the lab, showed that a drug developed by Burris and colleagues at Scripps Research Institute can stop cancer cells without causing damage to healthy cells or leading to other severe side effects. The Warburg EffectMetabolism – the ability to use energy – is a feature of all living things. Cancer cells aggressively ramp up this process, allowing mutated cells to grow unchecked at the expense of surrounding tissue. “Targeting cancer metabolism has become a hot area over the past few years, though the idea is not new,” Burris said. Since the early 1900s, scientists have known that cancer cells prefer to use glucose as fuel even if they have plenty of other resources available. In fact, this is how doctors use PET (positron emission tomography) scan images to spot tumors. PET scans highlight the glucose that cancer cells have accumulated. This preference for using glucose as fuel is called the Warburg effect, or glycolysis. In his paper, Burris reports that the Warburg effect is the metabolic foundation of oncogenic (cancer gene) growth, tumor progression and metastasis as well as tumor resistance to treatment. Cancer’s Goal: To Grow and DivideCancer cells have one goal: to grow and divide as quickly as possible. And, while there are a number of possible molecular pathways a cell could use to find food, cancer cells have a set of preferred pathways. “In fact, they are addicted to certain pathways,” Burris said. “They need tools to grow fast and that means they need to have all of the parts for new cells and they need new energy.” “Cancer cells look for metabolic pathways to find the parts to grow and divide. If they don’t have the parts, they just die,” said Burris. “The Warburg effect ramps up energy use in the form of glucose to make chemicals required for rapid growth and cancer cells also ramp up another process, lipogenesis, that lets them make their own fats that they need to rapidly grow.” If the Warburg effect and lipogenesis are key metabolic pathways that drive cancer progression, growth, survival, immune evasion, resistance to treatment and disease recurrence, then, Burris hypothesizes, targeting glycolysis and lipogenesis could offer a way to stop a broad range of cancers. Cutting off the Energy SupplyBurris and his colleagues created a class of compounds that affect a receptor that regulates fat synthesis. The new compound, SR9243, which started as an anti-cholesterol drug candidate, turns down fat synthesis so that cells can’t produce their own fat. This also impacts the Warburg pathway, turning cancer cells into more normal cells. SR9243 suppresses abnormal glucose consumption and cuts off cancer cells’ energy supply. When cancer cells don’t get the parts they need to reproduce through glucose or fat, they simply die. Because the Warburg effect is not a feature of normal cells and because most normal cells can acquire fat from outside, SR9243 only kills cancer cells and remains non-toxic to healthy cells. The drug also has a good safety profile; it is effective without causing weight loss, liver toxicity, or inflammation. Promising ResultsSo far, SR9243 has been tested in cultured cancer cells and in human tumor cells grown in animal models. Because the Warburg pathway is a feature of almost every kind of cancer, researchers are testing it on a number of different cancer models. “It works in a wide range of cancers both in culture and in human tumors developing in animal models,” Burris said. “Some are more sensitive to it than others. In several of these pathways, cells had been reprogramed by cancer to support cancer cell growth. This returns the metabolism to that of more normal cells.” In human tumors grown in animal models, Burris said, “It worked very well on lung, prostate, and colorectal cancers, and it worked to a lesser degree in ovarian and pancreatic cancers.” It also seems to work on glioblastoma, an extremely difficult to treat form of brain cancer, though it isn’t able to cross the brain/blood barrier very effectively. The challenge for researchers in this scenario will be to find a way to allow the drug to cross this barrier, the body’s natural protection for the brain, which can make it difficult for drug treatments to reach their target. And, in even more promising news, it appears that when SR9243 is used in combination with existing chemotherapy drugs, it increases their effectiveness, in a mechanism apart from SR9243’s own cancer fighting ability. Other researchers on the study include Colin A. Flaveny, Kristine Griffett, Bahaa El-Dien M. El-Gendy, Melissa Kazantzis, Monideepa Sengupta, Antonio L. Amelio, Arindam Chatterjee, John Walker, Laura A. Solt and Theodore M. Kamenecka. Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.
The no-diet approach to weight control By adopting sensible eating habits and practicing portion control, you can eat nutritious foods so that you take in as many calories as you need to maintain your health and well-being at your ideal weight. Often, weight loss occurs on its own simply when you start making better food choices, such as avoiding processed foods, sugar-laden foods, white bread and pasta (substitute whole-grain varieties instead), foods with a high percentage of calories from fat, alcoholic drinks. While nothing is absolutely forbidden, when you do succumb to temptation, keep the portion size small and add a bit more exercise to your daily workout. By replacing some unwise food choices with healthy ones, you'll be cutting back on calories. If you add some moderate physical activity, you have the perfect weight-loss plan without the need for special or inconvenient (and often expensive) diet plans. An example of a successful no-diet weight loss program A 45-year-old woman complains that she has gradually put on 12 pounds over the past year. In the last month, she's faced a stressful work deadline and added another 4 pounds to her frame. This individual's goal is to lose the 16 pounds she has gained. Since her weight has been gradually increasing, she knows that she is consuming more calories than she is burning, especially with her sedentary job. She decides that a weight loss of 1 pound per week (equal to a deficit of about 3,500 calories, or cutting 500 calories per day) would be acceptable and would allow her to reach her goal in about four months. She decides to make some changes that will allow her to cut back an average of 250 calories per day. Skipping a large glass of sweetened iced tea will save about 200 calories. Substituting mineral water for the cola she regularly drinks during meetings can save another 150 calories. Foregoing her morning muffin snack (or eating only half a muffin) can also save 250 calories or more. To reach her goal of a 500-calorie-per-day savings, she adds some exercise. Getting up early for a 20-minute walk before work and adding a 10-minute walk during her lunch break add up to a half hour of walking per day, which can burn about 200 calories. On weekends, she plans to walk for 60 minutes one day and spend one hour gardening the next day for even greater calorie burning. If walking for 60 minutes is too much, two 30-minute walks one day would burn the same number of calories. Twice per week she plans to stop at the gym on the way home from work, even if only for a half hour of stationary cycling or swimming (each burning up to 250 calories). By making just some of the dietary cutbacks mentioned and starting some moderate exercise, this individual can easily "save" the 3,500 calories per week needed for a 1-pound weight loss, leading to a healthy rate of weight loss without extreme denial or deprivation. Furthermore, her changes in diet and lifestyle are small and gradual, modifications that she can maintain over time. Superfoods Quiz: Test Your Diet IQTake our Superfoods Quiz! Get to know how unprocessed, raw, organic foods and healthy drinks are rich in nutrients and dietary...learn more » Childhood Obesity Quiz: Test Your Medical IQChildhood obesity has reached epidemic proportions. Take the Childhood Obesity Quiz to test your knowledge of the facts and...learn more » Belly (Abdominal) Fat Quiz: Test Your Belly Fat IQDid you know there is a medical term for belly fat? Find out what it is and learn why getting rid of belly fat may be the best...learn more » Fat and Fats Quiz: Test Your Diet IQTake this online Fat & Fats Quiz to learn if you really are what you eat!...learn more » Food Portion Distortion Quiz: Test Your Diet IQAre your portions deceiving you? Take the Food Portion Distortion Quiz to find out how and why gigantic portions trick you into...learn more » Healthy Eating at Restaurants Pictures Slideshow: Don't Abandon Your DietSee how to recognize the dangers and stay on your healthy diet when eating out. Watch this slideshow to learn about healthy...learn more »