DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Developing a Fingerprint for Renal Cell Carcinoma Progression

Posted March 8, 2016
Dr. Richard Drake, M.D., Medical University of South Carolina
Dr. Alexander Parker, M.D., Mayo Clinic and Foundation

Renal cell carcinoma (RCC) is the most common kidney cancer in adults. The incidence and mortality rate of RCC has steadily risen for more than 30 years with the most common form being the clear cell form of RCC (ccRCC). The primary treatment of ccRCC is surgical removal; however, a lack of detection for early stage cancers has left 25%-30% of surgical patients with a subsequent metastatic progression of ccRCC, despite no evidence of metastasis at the time of surgery. Therefore, it is necessary to develop early and accurate detection, staging, and follow-up of ccRCC for diagnosing and managing the disease.

In 2009, the CDMRP Peer Reviewed Medical Research Program awarded Drs. Richard Drake and Alexander Parker partnered Investigator-Initiated Research Awards to explore tissue and metabolic biomarkers of recurrent ccRCC. They proposed to identify tumor-associated proteins in patient specimens and to use an existing panel of biomarkers for ccRCC to develop a novel biomarker-based prognosis scoring system for identifying individuals at risk for recurrence. They used the cutting-edge technology of matrix-assisted laser desorption-ionizing (MALDI) mass spectrometry imaging in collaboration with Metabolon, Inc. for metabolic profiling. Not only did this study use the genomic information from patient samples, but they also explored the potential biomarkers at the protein, cell membrane, and metabolite level. They found that some biomarkers are carried forward from primary to metastatic ccRCC, but there is considerable variability between the primary and metastatic forms of ccRCC even within the same patient. This information will be of value in the development of future drug strategies based on multiple targets, rather than one specific target.

Furthermore, the methods used in this study are being applied to building bigger ccRCC tissue banks with emphasis on bisecting margin areas. This new approach of being able to assess tissue distribution of potential biomarker analytes provides new discovery tools for the clinic. Drs. Drake and Parker are currently working to validate a clinical-grade, noninvasive test that will give physicians a better understanding of cancer development so they can then tailor a treatment plan to fit a patient's individual needs. These efforts have strong potential to lead to better patient outcomes as well as lower health care costs.

Publications:

Powers TW, Jones EE, Betesh LR, Romano PR, Gao P, Copland JA, Mehta AS, and Drake RR. 2013. A MALDI imaging mass spectrometry workflow for spatial profiling analysis of N-linked glycan expression in tissues. Analytical Chemistry 85(20):9799-9806.

Jones EE, Powers TW, Neely BA, Cazares LH, Troyer DA, Parker AS, and Drake RR. 2014. MALDI imaging mass spectrometry profiling of proteins and lipids in clear cell renal cell carcinoma. Proteomics 14(7-8):924-935.

Links:

Abstracts for Dr. Drake
Public and Technical Abstracts: Tissue and Metabolomic Biomarkers of Recurrent Renal Cell Carcinoma

Abstracts for Dr. Parker
Public and Technical Abstracts: Tissue and Metabolomic Biomarkers of Recurrent Renal Cell Carcinoma

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Last updated Monday, March 7, 2016