Bcl-2 family member (BIM) expression and germline variants of BIM and phosphoinositide 3 kinase R1 (PIK3R1) might be candidate biomarkers for vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) in metastatic renal cell carcinoma (mRCC), findings presented at the American Association for Cancer Research (AACR) Annual Meeting 2016 have shown.1
Targeted therapy, particularly VEGFR TKIs including sorafenib, sunitinib, and pazopanib, has been the most efficacious therapeutic strategy for mRCC; however, approximately 35% of patients do not benefit from these agents due to resistance and/or treatment-related toxicity.
Previous research has demonstrated that TKIs induce BIM upregulation followed by acceleration of tumor cell apoptosis, and BIM germline deletion polymorphism has been identified as 1 of the primary mechanisms of resistance to various TKIs in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer and chronic myeloid leukemia. Further, the PIK3/protein kinase B(AKT) pathway has been found to be an important mechanism in various cancer cell growth, proliferation, and survival.
Therefore, researchers sought to evaluate BIM and germline variant PIK3R1 as potential biomarkers for VEGFR TKIs in mRCC. For the study, researchers analyzed tumor tissues and peripheral blood mononucleated cells from 124 patients with mRCC.
Results showed that 17.8% of samples had germline BIM deletion, and researchers found that BIM wild type demonstrated a trend toward poor prognosis with sunitinib or sorafenib treatment for clear cell mRCC. In addition, patients with high expression of BIM (> 50%) had a lower median overall survival than those with low or intermediate expression (P = .005).
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The study further revealed that 26% of 71 patients had the germline variant PIK3R1. Patients with PIK3R1 tended to have a poor prognosis following first-line VEGFR TKI therapy compared with those with wild type (P = .342).Progression-free survival following frontline sunitinib treatment was significantly worse for patients with the PIK3R1 variant vs wild type (P = .004).
- Kim JH, Kwon WS, Lee WS, et al. Novel biomarkers for VEGFR inhibitors in metastatic renal cell carcinoma: BIM expression, and germline polymorphisms of BIM and PIK3R1. Poster presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.