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Dr. Elizabeth Ellis received a 2024 Kidney Cancer Association Chromophobe RCC Focus Award in partnership with the Chromophobe and Oncocytic Tumor Alliance for research on “Evaluating the Response of Chromophobe Renal Cell Carcinoma to Novel Targeted Metabolic Therapies”. Dr. Ellis is a Urologic Oncology Fellow at MD Anderson Cancer Center in Houston, Texas. We spoke with Dr. Ellis about her research and the impact it could have on people with kidney cancer.

What is our current understanding about chromophobe renal cell carcinoma (chRCC) and where can the field go from here?

Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of kidney cancer, and 5-10% of patients with chRCC develop metastatic disease. We do not have a way to identify which tumors are aggressive and which are not. We know the gene mutations common to chRCC and that many chRCC tumor cells have multiple chromosome duplications and/or deletions. We also know that chRCC has an abundant amount of mitochondria compared to other kidney cancer subtypes. Because of this, we think there are important differences in the way cells make energy between chRCC and other kidney cancer subtypes. Once we better understand this, we may be able to develop drugs that target these mitochondrial pathways. 

The more we understand about tumors, the more we realize that no one tumor is the same. I think the field is moving toward precision medicine and using biomarkers to help predict response to certain treatments is going to be more heavily utilized once they have been identified and more rigorously tested.

What is your project about and how did you develop the idea?

This research project seeks to address two unmet needs. First, we have not yet identified biomarkers that can predict whether chRCC will respond to certain drugs targeting cancer cell metabolism. To address this, we plan to validate protein biomarkers that may differ between localized and advanced chRCC. We will also examine the differences in metabolic biomarkers between chRCC and the most common type of kidney cancer, clear cell RCC.

Second, metastatic chRCC does not respond to existing kidney cancer treatments, and there have been no clinical trials dedicated to chRCC treatments. Our group has developed a patient derived xenograft animal model of chRCC, which we can be used to test specific drugs of interest. ChRCC differs from other kidney cancer subtypes in the metabolic mechanisms it utilizes to make energy to divide. We can use these animal models to better understand this metabolic signature and identify potential drug targets. Once we better understand the metabolism of chRCC, we can develop new drug combinations that target these pathways to improve survival of patients with metastatic chRCC.

When I was a resident at the University of Rochester Medical Center, Rochester, NY, I developed a project to identify tissue biomarkers that would help determine if patients with chRCC had a high risk of recurrence. In fellowship, my goal was to externally validate my findings and build upon this foundation. We know that the way chRCC makes and uses energy is very important. Working with my mentor team, we decided to utilize our chRCC PDX animal models to further evaluate metabolism of chRCC and test thoughtful drug combinations from our findings.

What is the potential in researching rare cancer types?

Researching rare cancer subtypes at a large cancer center like MD Anderson is much easier because even though the cancer is rare, many of the patients with rare cancers seek care at these institutions. Because they treat and study a high volume of cases, the physicians and scientists at large cancer centers better understand the disease. Studying rare cancer subtypes can also help us better understand more common cancers. For example, in our study we plan to compare the way chRCC tumors use energy to the way clear cell renal cell carcinoma (ccRCC) tumors use energy and this, in turn, may help us better understand the most common subtype of kidney cancer, ccRCC.  

What about your research could be most exciting for patients and families?

If we can better understand how chRCC is different from other kidney cancers, we can identify new drug targets that ultimately exploit its vulnerabilities and develop new treatments specific to chRCC.

What motivates you?

You can always be better. As a former aspiring ballerina, this mentality was ingrained in me from a young age. Seeing patients with a diagnosis for which we do not always know the best treatment, pushes me back to the research bench to ask more questions and search for better answers. We have come so far in advancing our field, but we must remember that we can always jump higher, and I want to help take us as a field to that next height.

Being a urologist is also very personally rewarding. Many urologic conditions can make patients feel vulnerable. The ability to approach these situations with the utmost compassion is important to building trust and rapport with patients and is the key to understanding their perspective and wishes so you can tailor a curative treatment plan to the individual. This patient-physician interaction is one of the most fulfilling parts of my job. 

What else do you want others to know about you or your research?

Here at MD Anderson Cancer Center, I have the best team of mentors to guide this project – Drs. Jose Karam, Niki Zacharias Millward, and Pavlos Msaouel. Working with them over the past few months has already provided me with a wealth of knowledge. I continue to be impressed every day with their contagious dedication and enthusiasm toward advancing our knowledge and therefore treatments for kidney cancer.

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