Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas
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Brandon G. Smaglo1, Anteneh Tesfaye2, Thorvardur R. Halfdanarson3, Joshua E. Meyer4, Jue Wang5, Zoran Gatalica6, Sandeep Reddy6, David Arguello6 and Patrick M. Boland7
1 The Ruesch Center for the Cure of GI Cancers, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA
2 Departments of Hematology/Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA
3 Department of Medicine, Mayo Clinic, Rochester, MN, USA
4 Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
5 Division of Oncology, University of Arizona Cancer Center, Phoenix, AZ, USA
6 Department of Pathology, Caris Life Sciences, Phoenix, AZ, USA
7 Department of Medicine, GI Center, Roswell Park Cancer Institute, Buffalo, NY, USA
Brandon G. Smaglo, email:
Keywords: anal squamous cell carcinoma, biomarker analysis, tumor profile
Received: May 15, 2015 Accepted: October 09, 2015 Published: October 20, 2015
Anal squamous cell carcinoma (ASCC) is a rare, HPV-associated malignancy typically diagnosed in early stages and definitively treated with chemoradiation. In situations where patients exhibit metastatic or recurrent disease, treatment options are severely limited. In this study, molecular alterations were identified that could be used to aid in therapeutic decisions for patients with metastatic or recurrent anal squamous cell carcinoma. Specimens from patients with this cancer were tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing, protein expression by immunohistochemistry, and gene amplification with in situ hybridization. Utilizing these techniques, novel treatment strategies that could be explored were identified, including potential benefit with anti-EGFR therapies, immune checkpoint inhibitors, topoisomerase inhibitors, and taxanes. The frequency of overexpression of proteins that mark resistance to chemotherapeutic drugs, such as MRP1 (chemotherapy efflux pump), ERCC1 (resistance to platinum-based chemotherapy), and thymidylate synthase (resistance to fluoropyrimidines) were also identified, suggesting a lack of benefit. This multiplatform strategy could be explored for its potential to generate a personalized treatment selection for patients with advanced ASCC, provide a guide for future therapeutic development for this cancer, and be extended to other rare cancer types as well.
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