Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas

Brandon G. Smaglo, Anteneh Tesfaye, Thorvardur R. Halfdanarson, Joshua E. Meyer, Jue Wang, Zoran Gatalica, Sandeep Reddy, David Arguello, Patrick M. Boland

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)43594-43604
Number of pages11
JournalOncotarget
Volume6
Issue number41
DOIs
StatePublished - 2015

Keywords

  • Anus Neoplasms/genetics
  • Biomarkers, Tumor/analysis
  • Carcinoma, Squamous Cell/genetics
  • DNA Mutational Analysis
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Polymerase Chain Reaction
  • Transcriptome

Fingerprint

Dive into the research topics of 'Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas'. Together they form a unique fingerprint.

Cite this