One of ACKC’s principal objectives is to raise funds for kidney cancer research in order to find a cure for this disease. To that end, we raise funds privately, awarding grants to promising, innovative researchers, and, we advocate every year, during our Campaign for Federal Research Funding, requesting a Congressional appropriation targeted for kidney cancer research.
From the Federal Fiscal Year 2006 through FY2014, ACKC has been successful in having kidney cancer included as a disease eligible to receive grants from the Department of Defense’s cancer research program. Due to our efforts, the DoD has so far awarded $9.1 million in grants through FY2014 (FY2015 has not yet been awarded, but kidney cancer is again disease eligible) — see list of all recipients for a brief description of their work below.
Kidney Cancer Research Projects
Enhancing Immune Checkpoint Inhibitor Therapy in Kidney Cancer
FY2014 — $486,000
John Hopkins University, Baltimore MD
Project: Immune checkpoint inhibitors are showing promise in the treatment of metastatic kidney cancer, especially in some cases providing long-term of even complete response. However, the overall response rate hovers only around 20%. Dr. Hammers will alternately apply stereotactic radiation, cryoablation, or a toll-like receptor called imiquimod to metastatic kidney cancer cells to hopefully generate an immune response (called the abscopal effect) that will allow the body’s immune system to recognize the tumor antigen and thus significantly improve the response rate to subsequent treatment with the checkpoint inhibitor nivolumab (Opdivo).
Role of of Lisomal Transporters in Promoting the Growth of Clear Cell Kidney Cancer and Other Tumors
FY2014 — $585,000
David M. Sabatini
Whitehead Institute for Biomedical Research, Cambridge MA
Project: MTORC1 Is a protein complex that controls protein synthesis. MTORC1, when activated, is also a key growth signaling pathway in clear cell carcinoma (ccRCC). MTORC1 activation occurs at the lysosome, a structure in the cell that contains enzymes and which is responsible for intra-cellular digestion. MTORC1 is activated by nutrients and proteins in the lysosome, but it is not known which and by what mechanism nutrients are “sensed” by the MTORC1 pathway. MTORC1 has been targeted by two ccRCC cancer drugs, Afinitor and Torisel, but not very effectively. Dr. Sabatini will study the mechanism by which the nutrient levels in the lysosome activate MTORC1 in order to more effectively target this complex in ccRCC.
Validation of ZHX2 as a Novel VHL E3 Ligase Substrate and its Role in Kidney Cancer
FY2014 — $537,921
North Carolina University of Chapel Hill
Project: Disabling the VHL gene can lead to the development of clear cell renal cell carcinoma (ccRCC), and this relation is found in over 80% of ccRCC cases. It is known that VHL moderates the oncogenic transcription factor HIF-2α, whose presence promotes VEGF and other angiogenic factors that promote the growth and proliferation of ccRCC tumors. Dr. Zhang screened 17,000 proteins and found one called ZHX2, a transcription factor, similar to HIF-2α, that is also regulated by VHL, and which, based on preliminary research, may be linked to ccRCC tumor progression. His grant will answer the question if ZHX2 promotes the growth and spread of ccRCC, and, if so, will identify protein targets of kidney cancer therapy similar to anti-VEGF therapies.
Effects of Tobacco Smoke on Kidney Cancer
FY2013 — $474,560
University of Cincinnati
Project: There is very little information about the molecular mechanisms by which cigarette smoking promotes kidney cancer. This project will will perform a global analysis of gene sequences and activity in kidney tumors from male veterans who are heavy smokers (at least one pack of cigarettes a day for 20 years or longer), non-smokers (less than 100 cigarettes per lifetime), and data available for the general population of patients with kidney cancer, and compare the data from the three groups.
Investigating Drug Resistance and Rebound Effect When Treatment Ceases
Roswell Park Cancer Institute
Project: Use mouse kidney tumor models that mimic metastatic disease progression relevant for RCC patients. Specifically, identify molecular pathways that promote rebound regrowth (when treatment ceases) and drug resistance and metastasis, and to assess the benefit of VEGF pathway inhibition in the neoadjuvant treatment.
Enhancing mTOR Responsiveness FY
2012 — $364,000
University of North Carolina
Project: Although nTOR inhibitors extend life of metastatic kidney cancer patients, they do not shrink tumors significantly, generating mostly stable disease. Project will identify those kinases (proteins) that are up-regulated under m-TOR treatment and target them, in a pre-clinical setting, with known kinase inhibitors that can be combined with mTOR to kill the tumors cells thus increasing overall response.
Kidney Cancer Immunologically Enhanced Vaccine
FY2012 — $381,000
Roswell Park Cancer Institute
Project: Vaccines have the promise of inducing a long-lasting immune response in metastatic kidney cancer, however, they are modulated by regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs), all of which inhibit an anti-tumor response. This project, in a pre-clinical setting, will incorporate, with the vaccine, Foxp3 to deplete Tregs and tasquinimod to target MDSCs and TAMs in order to generate an enhanced anti-tumor response with the goal of transferring this combination into a clinical trial.
Role of Grainyhead in Kidney Cancer
FY2011 — $296,000
West Virginia University
Project: Epithelial-mesenchymal transition (EMT), where cells change their behavior, is an important determinant of tumor progression. Inhibition of EMT may decrease tumor invasion and metastasis, and an increase in EMT may accelerate tumor progression. The “grainyhead” gene suppresses EMT. In this project, the grainyhead gene’sexpression will be enhanced, and if it acts as a tumor suppressor, a therapy will be developed to help prevent recurrence of kidney cancer after initial diagnosis/treatment.
Using MRI to Diagnose Tumor Aggressiveness
FY2011 — $240,000
University of California, San Francisco
Project: Test the hypothesis that the aggressiveness of a kidney tumor can be measured by the metabolism of the cancer cells, which the researcher will measure by the use of a non-invasive MRI to calibrate the production of lactate, a byproduct of metabolism. This would allow one to differentiate the tumors as being benign, low-grade, or metastatic. If successful, one could clinically determine whether nephrectomy is required for a kidney tumor without having to do an invasive biopsy of the tumor.
Nanotechnology to Develop Urine Test for Kidney Cancer
FY2010 — $454,900
Project: Based on previous research, two specific proteins are found at much higher concentrations in the urine of people with clear cell and papillary kidney cancer than in healthy people. However, testing for these proteins is expensive and cumbersome. Project will develop an efficient and inexpensive test using nanotechnology to identify whether these proteins exist in the urine and thus to diagnose kidney cancer via a simple urine test.
Development of Kidney Cancer Blood Test
FY2010 — $1,004,018
Fred Hutchinson Cancer Research Center
FY2010 — $202,197
Project: Clear cell kidney cancer tumors generate specific minute particles that are released into the blood. This project will determine if the presence and density of these particles can be used to generate a simple blood test that would diagnose kidney cancer at an early stage. Eventually, want to develop a similar test to determine aggressiveness of the cancer.
Note: Dr. Maneesh Tewari from the Fred Hutchinson Cancer Research Center indicated to us that he would not have been able to pursue his idea to develop a blood test to diagnose kidney cancer if ACKC had not succeeded in having kidney cancer included as an eligible disease in the Department of Defense’s cancer research budget. He added that the DoD has a unique mechanism whereby a researcher can propose a project that can really break new ground. Their grant review process leads to cutting edge, innovative research being funded.
Use of MRSI to Investigate Tumors
FY2010 — $115,875
Zhen Jane Wang
University of California, San Francisco
Project: A new non-invasive imaging technique called magnetic resonance spectroscopic imaging (MRSI) can be used to determine the metabolic consistency of tumors. This project will investigate whether MRSI can determine kidney cancer tumor aggressiveness. If possible, MRSI could be used to diagnose small, indolent (slow growing) tumors that may not need invasive surgery. This technique has been successful in brain and prostate cancers.
Tissue and Metabolic Markers for Recurrent Kidney Cancer
FY2009 — $602,700
Mayo Clinic, Jacksonville
Eastern Virginia Medical College
Project: Identification of kidney cancer markers that could predict for aggressive or recurrent disease, which could then inform therapeutic options. The implication of this is that those patients at high risk of recurrence can be advised to have adjuvant therapy and those at low risk can be advised to further spread out their follow-up radiological exams, thus reducing their radiation exposure.
Targeted Nanoparticles for Kidney Cancer Therapy
FY2009 — $599,933
Wake Forest University
Project: Develop nanoparticles (1/1000 size of human hair) that will target and bind to kidney cancer tumors and metastases, which then will be illuminated and destroyed by infrared radiation that is directed only to the cancer cells thus preserving normal cells and reducing toxicity.
The Role of RASSF1A Tumor Suppressor in Kidney Cancer
FY2008 — $721,800
University of Louisville
Project: Create kidney cancer in a mouse (rather than implanting human cancer in a mouse) to develop an exceptionally useful tool for cancer researchers. Also will determine the role of RASSF1A, a cancer suppressor gene, which is silenced in clear cell kidney cancer.
Identification of Genes in Kidney Cancer Oncogenesis
FY2006 — $932,900
Maria F. Czyzyk-Krzeska
University of Cincinnati
Project: Identification of genes involved in the causation of clear cell kidney cancer, which could then be targeted by therapy.