Q&A: Dr. Abraham Hakimi, 2014 KCA Grant Recipient

In honor of our 30th anniversary, we’re catching up with former grant recipients to hear how their work has impacted kidney cancer care and research.

Dr. Abraham Hakimi is a urologist and researcher at Memorial Sloan Kettering Cancer Center in New York where he co-leads the Translational Kidney Cancer Program with Dr. Robert Motzer. Dr. Hakimi received the 2014 Andrew C. Novick & P.H.M de Mulder/ AUA Urology Care Foundation Research Scholar Award, supported by the KCA. We spoke to him about his research project – Interrogation of the Sorbitol Pathway in VHL-Independent HIF driven Renal Cell Carcinomas – and what he’s been working on recently.

What was the inspiration for the research you were granted funds for? How did the project come together?

I studied kidney cancer as a surgeon in both early and advanced diseases. I had done a study where we looked at how metabolism is altered in tumors and in normal kidney cells. While focused on clear cell renal cell carcinoma, we saw two tumors that were outliers. Instead of being clear cell carcinoma, they turned out to be clear cell papillary tumors. We found this to be a strong signal as it formed the basis for the project’s rational. The metabolic phenotype of these tumors was about the fourth most common form and we ended up finding a cool and unique pathway in these tumors. We proceeded to do more characterization and this grant was really instrumental in continuing to lay the groundwork of this research.

What was the outcome of the research project? Have there been further outcomes or developments following the award period?

We ended up determining that this tumor type is driven by unusual metabolic pathways involving sugars, fructose and sorbitol and are very high only in this tumor type. This was confirmed when we tested a larger cohort of these tumors, then published papers describing how these tumors are different. We also looked at clinical factors in these tumors and the entire MSKCC experience with clear cell papillary kidney cancer and found that they never developed metastasis during our study. This was very important to research.

How would you say your research project contributed to the field? 

It helps to define the metabolic phenotypes for clear cell, which is the most aggressive and common kidney cancer type, and for rare variants, which make up 30 to 40 percent of kidney cancer types. It’s important to understand natural history and biology of tumors as they can be used to approach treatment a surveillance plans for patients.

What did you find most exciting or significant about your research? How would you explain this to a person with kidney cancer?

 I find it interesting that clear cell papillary tumors have some of the classic hallmarks of clear cell– the activation HIF pathway (the calling card for clear cell) despite having none of the mutations of clear cell, like the VHL gene. There must be a non-genetic way for clear cell papillary tumor to activate HIF. This is very important to recognize that different ways can activate the same pathway.

Did this research project impact your approach to patient care?

When we see patients with this now, we can be increasingly confident that this tumor isn’t going to come back and threaten their life. From a patient’s perspective, it is good to know that clear cell papillary kidney cancer is essentially benign or at worse very indolent. This is a gratifying conversation to have.

What is your research focus now? 

I continue to have a strong interest in non-clear cell kidney cancer and focus more on advance kidney cancers in general. A lot of the metabolism and immune microenvironment in rare kidney cancers are different from clear cell which may help explain which patients do and do not respond to immunotherapy. There are emerging ways to target the metabolic pathways in these and this can improve the way to treat patients.

Is there anything else you’d like patients and families about the impacts of your work?

The most important thing is that patients should stay engaged with their disease and push their clinicians, scientists, and surgeons to continue to study rare kidney cancers. We have made a lot of headway in treatments in the last decade.