Chromosomal Changes Predict Clinical Response to Sunitinib in RCC

Clinical response can be challenging to predict in some cancers, but new research has shown the ability to predict response to sunitinib (Sutent) in patients with advanced renal cell carcinoma (RCC).

Chung-Han Lee, MD, and colleagues were interested in learning more about RCC and why 20% to 30% of patients' tumors become resistant to sunitinib, the first-line therapy for clear cell RCC.

Dr. Lee presented their findings in a poster session (abstract 4552) at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29-June 2, 2015 in Chicago. The findings can also be found in the May 2015 online issue of the Journal of Clinical Oncology.¹

Their study sought to identify the chromosomal copy number changes that are associated with sunitinib clinical response. Copy number variations are deletions or duplications of a segment of DNA. These variations can involve gains or losses of genomic DNA that are either microscopic or submicroscopic, and may not be visible by standard G-banding karyotyping.²  Karyotyping is a test to examine chromosomes in a sample of cells, which can help identify genetic problems as the cause of disease.

Whole genome comparative genomic hybridization (aCGH) was performed on pretreatment tumor derived DNA from 76 patients who had been given sunitinib. This process identified differential copy number alterations. Using databases comprising of patients who had not yet been given sunitinib (TCGA-436 and University of Tokyo-240), these alterations were not correlated with overall survival, suggesting that these alterations reflect sunitinib response, and not sunitinib-independent tumor biology.

The researchers concluded that an aCGH analysis of sunitinib-treated clear cell RCC patients revealed multiple novel copy number alterations associated with clinical response. Further study will provide more insight into how exactly sunitinib resistance occurs and how the mechanisms work, but these appear to be positive findings.

References:

• American Society of Clinical Oncology Annual Meeting. (2015). Novel chromosome copy number changes to predict clinical response to sunitinib in patients with advanced renal cell carcinoma.
• Shlien A, Malkin D . (2009). Copy number variations and cancer. Genome Medicine, 1(6): 62.