Two researchers from the Department of Urology were both granted DOD Kidney Cancer Research Program Concept Awards. This particular grant supports innovative and potentially groundbreaking novel concepts in kidney cancer research.

Department instructor, Anirban Kundu, Ph.D., and staff scientist, Suman Karki, Ph.D., both received the award for their kidney cancer research initiatives and work alongside Sunil Sudarshan, M.D., department professor and head of the kidney cancer research lab.

Kidney cancer is the seventh most common type of cancer in the US with over 81,000 new cases and 14,000 deaths estimated in 2023. Kidney cancer is considered one of the top ten malignancies in both men and women in the United States alone. The disease is often diagnosed at an advanced stage after it has already progressed or metastasized to other organs which often leads to death within 2-3 years.

Anirban Kundu, Ph.D.

Dr. Kundu was awarded the DoD Concept Award for his proposed research on the relationship between semaphorins and immunotherapy resistance in kidney cancer calls.

Recently, immunotherapy has shown promising results in treating advanced-stage and metastatic kidney cancer cases.

Immunotherapy is a type of cancer treatment that helps promote the body’s natural defenses to fight cancer. Immune cells use “checkpoints” to avoid attacking normal cells in the body. Immunotherapies help to inhibit these checkpoints to allow the immune cells to kill cancer cells in the system. Sometimes, blocking checkpoints can lead to immune cells killing normal cells as well, which can lead to autoimmunity. Traditional immunotherapy treatments only help a small percentage of kidney cancer patients, which is why scientists are trying to develop highly specific and targeted immunotherapies for the disease.

Semaphorins are proteins found in multiple parts of the body that serve similar or different biological functions.

“As semaphorins act to feeble cell-to-cell communication, it’s logical to think that tumors bearing high amounts of semaphorins will have a loose connection with immune cells in the tumor microenvironment, resulting in a weak anti-tumor immunity,” says Kundu, “However, semaphorins as tumor intrinsic factors are less explored in the context of modulating anti-tumor immunity. In large clinical data sets, some semaphorins are found to be highly abundant in kidney cancer compared to any normal tissues.”

Dr. Kundu’s proposal is a proof-of-principle study to find out the roles of semaphorin(s) in immunomodulation and immunotherapy resistance in kidney cancer.

Suman Karki, Ph.D.

Dr. Karki was awarded the DOD Concept Award to investigate the specific role of abnormal serine metabolism in the proliferation and metastasis of clear cell renal cell carcinoma (ccRCC) to distant organs. Clear cell renal cell carcinoma (ccRCC) is the most common type of renal carcinoma and makes up 85% of all kidney cancer cases.

Cancer cells have specialized metabolic pathways that promote their proliferation, metastasis, and immune evasion. This is also known as metabolic reprogramming and ccRCC displays rewiring in the metabolism of amino acids that are believed to enable ccRCC to maintain its proliferation and adaptation to nutritional stress. Reprogramming of metabolic pathways for the biosynthesis of glycoproteins, proteoglycans, and glycolipids are essentially dependent on aberrant utilization of glucose and amino acids. Karki attests that nutrient availability affects the metabolic behavior of cancer cells, and therefore serine induced glycosylation could be a key factor.

“The successful completion of this study will provide insight for strategies that limit amino acid availability to block tumor progression,” says Karki.

Serine is the second most used amino acid by cancers, however, its role in promoting invasive phenotype and metastasis is not explored. Karki and his team aim to investigate how the altered metabolism of serine impacts glycosylation, and its effect on the proliferation and metastasis of ccRCC.