TY - JOUR
T1 - Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas
AU - Smaglo, Brandon G.
AU - Tesfaye, Anteneh
AU - Halfdanarson, Thorvardur R.
AU - Meyer, Joshua E.
AU - Wang, Jue
AU - Gatalica, Zoran
AU - Reddy, Sandeep
AU - Arguello, David
AU - Boland, Patrick M.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Anus Neoplasms/genetics
KW - Biomarkers, Tumor/analysis
KW - Carcinoma, Squamous Cell/genetics
KW - DNA Mutational Analysis
KW - High-Throughput Nucleotide Sequencing
KW - Humans
KW - Immunohistochemistry
KW - In Situ Hybridization
KW - Polymerase Chain Reaction
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=84952948280&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6202
DO - 10.18632/oncotarget.6202
M3 - Article
C2 - 26498363
AN - SCOPUS:84952948280
SN - 1949-2553
VL - 6
SP - 43594
EP - 43604
JO - Oncotarget
JF - Oncotarget
IS - 41
ER -