AACR-Kure It Cancer Research Partnership Makes Impact on Kidney Cancer
Kidney cancer is among the most common cancers in the United States. To help make a difference in the lives of kidney cancer patients, the AACR has partnered with Kure It Cancer Research since 2012 to support innovative translational kidney cancer research. Kure It is a nonprofit organization dedicated to fund research for kidney cancer and other underfunded cancers. Researchers supported by the AACR-Kure It partnership have made progress against kidney cancer on multiple fronts. Here are some of the highlights:
Molecular analyses of kidney cancers for targeted treatment
- 2012 AACR-Kure It grant recipient William Y. Kim, MD used technology called multiplex-inhibitor bead/mass spectrometry to analyze the activation state of proteins in kidney tumor samples. He developed a method to classify tumors based on the status of 17 proteins. Moving forward from the AACR-Kure It grant, Dr. Kim is continuing his efforts to molecularly characterize renal cancers with the end goal of identifying precision therapeutic strategies. He is the interim Director for Precision Oncology at the University of North Carolina Lineberger Comprehensive Cancer Center.
- Another 2012 AACR-Kure It grant recipient, James W. Mier, MD, determined that response to sunitinib was influenced by the activation of the tumor suppressor protein p53. This finding was supported by data from others that found mutations in p53 in a subset of sunitinib nonresponders.
Dr. Meir also used his grant to characterize the mechanisms behind the synergy of a drug that blocks a protein called MDM2 with drugs that block the angiogenic protein VEGF. He found that the synergy was due in part to depletion of a protein that contributes to kidney cancer development called HIF2 alpha.
Dr. Meir continues to identify novel treatment strategies for kidney cancer as a Phase I Oncology specialist at the Beth Israel Deaconess Medical Center.
Leveraging immunotherapy to treat renal cell cancer
- Immune checkpoint inhibitors (ICIs) are now approved for renal cell cancer treatment. However, it is still unclear how to identify which patients are more likely to respond to these therapies. 2015 AACR-Kure It grant recipient Eliezer M. Van Allen, MD analyzed hundreds of kidney cancer samples and found that the loss of a gene called PBRM1 is associated with response to ICIs. He published these findings in a high impact article in Science. This finding is especially important given that the PBRM1 gene is commonly mutated in clear cell renal cell carcinoma, and the importance of PBRM1 mutations in renal cell cancers remains evident as demonstrated in more recent work published by Dr. Van Allen and his colleague Nature Medicine, another high impact publication.
- 2018 AACR-Kure It grant recipient Kimryn Rathmell, MD, PhD is exploring how the tumor microenvironment influences the response of kidney cancer patients to immunotherapies. Her laboratory had previously observed that immune cells that infiltrate kidney cancers have defects in their metabolism. Potentially, the tumor-killing activity of these immune cells can be improved by addressing these metabolic deficiencies. In a recent publication, her group showed that stimulating these tumor-infiltrating immune cells with an antibody targeted against a protein called CD28 improved the metabolic characteristics of these immune cells, making them more effective against cancer cells.
The eight-year partnership between AACR and Kure It has helped support research that may improve treatment of kidney cancer patients.