Starving cancer away | Sophia Lunt | TEDxMSU

I love candy does anyone else like candy a lot of you well so do cancer cells cancer cells love sugar as many of you know cancer remains the second leading cause of death in the United States which means we still need better therapeutics for our cancer patients today I'd like to tell you about an exciting new approach to cancer therapy based on sugar metabolism we've actually known for a long time that cancer cells love sugar almost a hundred years ago in 1924 a famous German scientist and Nobel laureate named Otto Warburg observed that cancer cells eat a lot more sugar than normal cells so this observation that cancer cells love sugar is known as the Warburg effect and the Warburg effect tells us that normal cells can stop after just one piece of candy but cancer cells can't stop eating candy and we do take advantage of the Warburg effect for diagnosis of cancer through PET imaging here's a PET scan of a patient with pancreatic cancer the patient was given radioactively-labeled glucose which lights up when it concentrates in an organ the pancreas normally doesn't light up because it normally doesn't like to eat so much sugar but in this case the patient has cancer cells in the pancreas it's eating up all the sugar concentrating it and causing it to light up in the PET scan and we're able to diagnose the patient so it's good that we're taking advantage of sugar metabolism and the Warburg effect for cancer diagnosis but I want to take it a step further and use it for therapy well in addition to eating a lot more sugar cancer cells also metabolize sugar differently there are two major ways to metabolize sugar one way is to use oxygen which we breathe in and convert it to carbon dioxide which we breathe out if we don't have enough access if we don't have access to enough oxygen we can also convert sugar to lactate also known as lactic acid and we've all experienced this during exercise when we're unable to deliver enough oxygen to our muscles we run out of breath and we start getting lactic acid buildup and we feel that muscle burn from an energy point of view it's much better to metabolize sugar using oxygen because you can generate up to 36 energy molecules called ATP's if you convert sugar to lactate you only generate up to - well normal cells take sugar use oxygen and convert sugar to carbon dioxide generating a lot of energy molecules but cancer cells eat a lot more sugar and they convert most of it to lactate even when they have plenty of oxygen available and they don't generate much energy so why would cancer cells use such an efficient metabolism well to answer this question we have to think about what a cancer cell needs a cancer cell needs to grow and divide and make more cancer cells and you can't make more cancer cells simply with energy just as you can't build a new house simply with electricity so yes we can make energy from sugar but we can make other things like DNA and RNA which serve as the genetic blueprints for the cell just as you will need a blueprint to build a house you can also generate carbohydrates proteins and fats just as you will need building blocks concrete insulation and other items to build a house and we think that the Warburg effect supports all these biosynthetic pathways that generate cellular building blocks and if we want to take advantage of the Warburg effect we have to understand it in more detail so our favorite form of sugar is called glucose and glucose is metabolized mainly through a pathway called glycolysis which has many steps that eventually generates a metabolite called pyruvate without oxygen you can generate lactate from pyruvate with oxygen you can generate carbon dioxide now the enzyme that generates pyruvate is called pyruvate kinase and it's altered in all cancer cells there are actually two major forms or isoforms of pyruvate kinase M 1 and M 2 and one is found in many normal adult cells meaning these cells are no longer growing M 2 is found in every cancer cell study to date but to make things more complicated it's also found in some normal growing cells so what I did in the laboratory was to delete pyruvate kinase M 2 from both normal and cancer growing cells and see what would happen and here's what I found normal cells grow well as you can see in the yellow line with pyruvate kinase M 2 and when I delete it they completely stop growing as you can see in the red line when I do this to cancer cells they're able to grow with or without em - so how are they doing this is their metabolism changed are they rewiring their metabolism in order to do this we have to be able to look at their metabolites and we can't just put them under a microscope and look at metabolites it's too small so we need very expensive and sensitive experiments I've been told that this looks like a Slurpee machine but this is actually a very expensive instrument called a mass spectrometer and it can detect thousands of metabolites based on a molecules mass these are instruments that otto warburg did not have but we have access to them and we can study cancer metabolism in great detail and I want to show you my data using this instrument but before I do I don't want you to look at the words I want you to look at the colors is it black or do you see a lot of colors if it's black that means no metabolites are changing if you see a lot of colors the metabolites are changing so let's take a look as you can see these cancer cells are completely changing their metabolism they're increasing their metabolites in yellow and decreasing their metabolites in blue so that they can still grow without em - so it's like this if cancer cells are invading what this Wharton Center at Michigan State University and we figure out that they're coming in through Wilson Road so what do we do well we block Wilson Road we delete that road so they can't get in and what do they do they find a new way in they rewire their route even though it has more traffic and it's more indirect they still find the way in so without em - normal cells stop growing and cancer cells continues to grow by rewiring their metabolism so what I'm doing now in the laboratory is blocking multiple roads at once multiple genes so that cancer cells stop growing while normal cells continue to grow so we just talked about glycolysis and pyruvate kinase but metabolism is much more complicated than this and I want to give you an idea of that so I'm going to shrink glycolysis and move it to the upper left corner of your screen and now I'm going to fill in the rest of metabolism so take a deep breath and let it out as you can see metabolism is very complicated and this is still just a simplified map of metabolism and remember normal cells came from cancer cells so some pathways are shared and some pathways are different which means we have to understand normal complicated metabolism as well as cancer complicated metabolism but this is a very exciting Avenue for therapy because here are just some of the enzymes that are mutated deleted or somehow altered in cancer cells so these are all potential targets for therapy so here's our research strategy first I want to identify all the key metabolic pathways that help cancer then I want to do deeper mechanistic studies that tell us exactly how each pathway is helping cancer cells does it help their survival their growth or their invasion or something else then I want to take all of this information and use it to design personalized therapy because as you know all individuals are different with their own genetics diets and environments so we have just begun to understand different metabolism and cancer and taking advantage of it for therapy there are many different types of cancers with all kinds of mutations but they all have one thing in common they all have to eat cancer cells have altered sugar metabolism and I want to starve cancer you you

Channel: TEDx Talks

Views: 1,377,560

Rating: 4.7909789 out of 5

Keywords: TEDxTalks, English, United States, Science (hard), Biology, Biotech, Cancer

Id: f6rSuJ2YheQ

Length: 10min 30sec (630 seconds)

Published: Fri Apr 15 2016

Reddit Comments

[u/YOUREABOT]

Sophia have you looked into the effects of intermittent fasting and cancers ability to alter its metabolism to consuming ketones only?