Abstract
Abstract Background: The survival of patients with advanced metastatic osteosarcoma is poor with limited therapeutic options. Conventional therapies have reached a plateau. There is an urgent need for new rational targeted therapies based on identified biomarkers. Recently, theranostic molecular profiling services for advanced cancer patients by CLIA-certified commercial companies as well as in-house profiling in major academic medical centers has expanded exponentially. Using this technology, we evaluated molecular profiles of patients with advanced osteosarcoma. Patients and Methods: We conducted an observational chart review of patients with advanced metastatic osteosarcoma referred to Clinical Center for Targeted Therapy and/or Department of Pediatrics at MD Anderson Cancer Center (MDACC) whose tumor tissue had been analyzed by one of the following methods: 1. 182 gene next-generation exome sequencing (Foundation Medicine, Boston, MA), 2. Immunohistochemistry (IHC)/ PCR-based panel (CARIS Target Now, CARIS Life Sciences, Phoenix, AZ), 3. Single-gene PCR assays, PTEN IHC (MD Anderson Cancer Center CLIA pathology laboratory), 4. UT Houston Medical School IHC based morphoproteomics (Dr. Brown, Houston, TX). Results: 10/18 pts had profiling data (Foundation One, N=3, Caris N=2, UT MDACC CLIA, N=7, Morphoproteomics, N=2). Median age at presentation was 17.5(9-65). Most of the patients were heavily pretreated and had more than one profiling done (median no of prior therapies was > 5). M: F= 12:6. One patient had a history of retinoblastoma. Identified aberrations included PTEN loss (N=4), MYC amplification (N=1), P53 truncation or mutation (N=2), BCL2L2 amplification (N=1), NKX2-1 amplification (N=1), RB1 loss or mutation (N=2), PIK3CA mutation (N=1), EGFR amplification (n=1) and JUN amplification (N=1). IHC-based morphoproteomics showed increased expression of p-ERK1/2(Thr 202/Tyr204), p-mTOR (Ser 2448), and TRAIL(DR4) in 2 patients and p-IGF-1R(Tyr 1161) in 1 patient. Single-gene PCR-based assay for specific aberrations found no aberrations in 5/5 patients. Conclusions: Theranostic molecular profiling services are rapidly evolving. Advanced osteosarcoma molecular profiling revealed many aberrations in the PIK3CA/PTEN/mTOR pathway. Actionable aberrations exist and may be detected in subsets of advanced osteosarcomas. Further large-scale investigations are needed to evaluate the clinical benefit of matching patients with actionable aberrations identified using commercially available profiles. Citation Format: Rishi Agarwal, Daniela Elizabeth Egas Bejar, Fernando Francisco Corrales-Medina, Filip Janku, Michael Deavers, Razelle Kurzrock, Pete Anderson, Vivek Subbiah. Molecular profiling for actionable aberrations in advanced osteosarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4387. doi:10.1158/1538-7445.AM2013-4387
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