Dr. Akash Kaushik is a postdoctoral researcher at the Children’s Medical Center Research Institute at UT Southwestern where he studies cancer cell metabolism, which includes all the processes that help cells take up nutrients and convert them to energy and other materials for growth.
Dr. Kaushik received a 2019 Young Investigator Award for research that will take a closer look at the amino acid glutamine – a major source of energy and growth for some cancer cells – and its role in cellular activity. In particular, he will investigate how effective a glutaminase inhibitor is as part of renal cell carcinoma (RCC) tumor suppression pathways in vivo using mouse models. He will also study a key energy-generating cellular process called the tricarboxylic acid (TCA) cycle (also called the citric acid cycle or the Krebs cycle) and the effect of TCA inhibitors in cells with some mutated tumor suppressor genes.
We spoke to Dr. Kaushik about his work and what it means for patients.
For any cells to grow and proliferate, they need to make energy and spend it on cell growth. This pathway is very important for growth of normal cells in the body. In contrast, cancer cells rewire this pathway to generate energy and biomass required for sustained proliferation, and glutamine (an amino acid) supports the activity of this pathway. Here is the opportunity – if you can target this pathway you can target tumor cells and leave the normal cells. This metabolic liability can be used to develop novel drugs in combination with glutaminase inhibitor.
Previously, this phenomenon was studied in cells grown outside [a live model]. Now, we demonstrate that glutamine fuels the TCA cycle in kidney tumors grown in a mouse, which means it should eventually be true in patients also.
We identified that glutamine is a nutrient source that feeds into the TCA Cycle in RCC patient-derived xenograft models. It’s an opportunity for other investigators to ask what other tumor types can engage in glutamine metabolism. It also opens up a lot of important avenues for us to systematically study glutamine’s contribution as a major nutrient source in kidney tumors Especially if we can understand why certain tumors use glutamine as a fuel source for the TCA cycle, we can deploy glutaminase inhibitor in a more effective way.
This project brings a lot of bench work that has been done for decades to an in vivo model. I’m really excited because now we have a model to quickly test the efficacy of some of the clinical drugs and translate them to patients – bringing the findings from the benchside to the bedside.
For a long time, the field has evolved by studying cancer cells outside the body. We are now evaluating tumor metabolism in patient bodies by using mouse models – in vivo – so many findings are easily translated to a patient’s system. Once we can get a better understanding of the metabolic dependencies of kidney tumors on glutamine, we can identify novel therapeutic targets that may help develop new therapies.
I’m excited to find a tumor type that uses glutamine in a way that was previously thought to be non-existent. It’s an opportunity to study all the aspects of glutamine metabolism in vivo.
We’ve studied cancer metabolism for years now but sometimes failed to translate what we find in a tissue culture to an in vivo mouse model or a patient because many aspects can’t be translated. You can’t capture the tumor environment in vivo in a petri dish.
This exciting model shows a promising use of glutamine in the TCA cycle. We have identified some additional pathways that are active in kidney tumors, and targeting these pathways along with glutaminase inhibitor can be developed into new therapies.
The thought of really trying to understand what is happening drives me far. The support and guidance of my mentors, friends, family, and my wife help keep me passionate. When things unfurl, you really need the support of your loved ones and mentors to remind you that this is a hump in the road, everyone faces them, and once you cross it you will see that you’re contributing to the betterness of human kind by understanding the biology of cancer.
It’s a long road for research to make it from the benchside to the bedside. But the exciting results of this project makes me really feel like we are really and quickly improving and bring some info that would be useful for patients in the near future.
I’m thankful for the support from the KCA and my mentor, and I also want to thank the patient community because they’re really important. I also want to point out that we use a lot of animal models to conduct studies and we feel connected to them. We’re fortunate to have them and I thank my animals all the time for their contribution to the betterment of human life.