Salk Cancer Center

Daniel Hollern:
I got involved in cancer research after my grandfather was diagnosed with cancer. I remember the feeling that I had when I learned that there were no treatment options that could help my grandpa. It just devastated me, and it felt so unfair that I knew that science was going to be the only thing that would be able to help people like my grandfather. And so that was what drove me to cancer research with this idea that we have to develop therapies that provide options to people that have none.

Reuben Shaw:
For centuries, doctors and scientists have been trying to defeat cancer. And in spite of intensive effort, cancer has remained one of the most difficult diseases to treat. One of the few things in common across the hundreds of different types of cancer is the fact that regardless of what tissue it started in or which specific genes are altered in it, all cancers start to grow and divide more rapidly than the normal cells around them.

And in order to divide and grow so much faster, they have different dietary needs. They have different metabolic needs. They have to take up more sugars, more glucose, more amino acids, and more lipids from our diet or from the neighboring cells. And so scientists now understand that one way or another, tumor cells will rewire the biochemical pathways that make up their metabolism. That's why here at the Salk Cancer Center, we have a collaborative team of experts with different strengths that are attacking cancer from different angles. We are targeting cancer metabolism as a way to attack all cancers, including the hardest-to-treat cancers.

Christian Metallo:
Every cell in the body has to eat in the same way that we eat food. But a cancer cell starts to become deranged in what it eats, and how it grows, and how it uses that food. And the goal is to try to cut off that supply line. What we hope to do is just push them over the edge, so that they really can't survive.

Susan Kaech:
My lab is trying to understand how tumors can metabolically hijack the immune cells in the environment. For instance, by consuming extra nutrients that the immune cells and the T cells might use, but also by providing ones that they don't need. And so we're trying to figure out how we can reprogram or rewire those immune cells, those T cells, to function better in that environment. The Salk Institute is a hotbed for metabolism research. And coming together with cancer biologists, and immunologists, and trying to find this intersection of how these cell types are metabolically regulated.

Daniel Hollern:
Changes in metabolism can alter how well a cancer patient will respond to therapy. And my lab has discovered that specific type of immune cell, called a B-cell, delivers the most effective antitumor immune responses to therapy. And what makes B cells so special is that they can overcome the many challenges that tumors present, including harsh metabolic microenvironments.

Gerald Shadel:
We can't really talk about the role of metabolism in cancer without talking about mitochondria. Mitochondria are structures in your cells called organelles, which were basically take the food that you read and convert that into a source of chemical energy called ATP that your cells, tissues, and organs utilize to do basically everything they need it to do. Mitochondria are also sort of an armory of metabolites that the cell needs to proliferate to survive and to withstand stress. For this reason, cancer cells actually take advantage of this. They co-op mitochondrial metabolism to allow them to obtain their high growth potential, and to survive, really, the harsh environment of the tumor.

Christina Towers:
A key part of cellular metabolism is the ability of the cells to recycle some of the nutrients that they've already used up. And this allows them to conserve energy. And just like we think of recycling in our houses, it's a way for the cells to continue to grow with less input and still be able to continuously divide. And you can imagine in a tumor, which lacks a lot of nutrients, it's hard to get oxygen, hard to get blood supply in. Being able to recycle its own nutrients is a huge advantage for the cancer cells. And so being able to target this core metabolic process really may be a insight into how we can kill these cancer cells.

Alan Saghatelian:
My lab develops new technologies for studying metabolism. While a lot of my colleagues are experts in biology and have key questions, we actually develop new tools mostly using a technique called mass spectrometry. And what it does is it really allows us to detect and quantify thousands of metabolites from complex mixtures. 20, 30 years ago, these experiments were really not feasible because we didn't have the technology there. Now, I can take a diseased cancer cell versus a normal cell, and I can look really broadly across all of the metabolites and tell you which ones are changing, or we can study a specific pathway in greater detail and understand how quickly that pathway is turned on in a cancer cell versus a normal cell.

Satchin Panda:
Having circadian rhythm makes sure that our metabolism, immune system, and cell division are tightly controlled. Not too much. Not too little. And my lab has made the discovery that we can be master of our circadian rhythm by eating within a consistent window of eight to 10 hours every single day. And when we do this, our metabolism remains [inaudible 00:06:20], our cancer cells cannot grow too fast, and that ensures that having good circadian rhythm prevents many types of cancer.

Ronald Evans:
For nearly 40 years, my lab has identified and defined genes called nuclear receptors. They control how specific tissues in our body respond to diet, hormones, and exercise. In labs here, while small, the nature of the interactions expands their capacity to do novel work. And the nature of the research is so captivating that people here from all around the world just want to work all the time. And that's what makes a difference. It's passion. It's thoughtful approaches. It's instinct. And by putting all those together, you get something really new.