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Biomarker analysis identifies potential therapeutic targets for squamous cell anal carcinomas

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Squamous cell anal carcinomas are rare, but are very difficult to treat and often result in recurrence or metastases following standard treatment. A team of researchers from Roswell Park Cancer Institute (NY, USA), led by Patrick Boland (Roswell Park Cancer Institute), have conducted a multiplatform biomarker analysis in conjunction with Caris Life Sciences (TX, USA) in order to identify new therapeutic targets for the disease.

The team analyzed 212 tumor samples utilizing a combination of gene sequencing (Sanger or next-generation sequencing), protein expression (immunohistochemistry) and gene amplification (CISH or FISH assays). For 80.2% of the samples, tissue from a metastatic site was also analyzed.

The results of the study indicated significant immunohistochemistry overexpression in several genes: MRP1, in 97.6% of the analyzed samples; EGFR, 89.7%; TOPO1, 68.3%; MGMT, 67.2%; and PTEN, 46.9%. EGFR and HER2 were amplified in 7.4% and 1.8% of the cases, respectively. In addition, high mutation rates were observed in biomarkers associated with the PIK3CA/Akt pathway (PIK3CA, FBXW7, PTEN and Akt1), and PIK3CA exon 9 mutations were detected in 75% of all PIK3CA mutations.

“Our findings are exciting, as we were able to identify several potential biomarkers that can be targeted with existing therapies. Drugs that target the PI3 kinase pathway and ErbB-family receptors may prove to be particularly effective in these cancers, for instance anti-EGFR agents or newer pan-HER inhibitors,” commented Boland. “Additionally, our results suggest that this approach may also be similarly effective in identifying targets in other tumors of viral origin.”

The findings were presented recently at the ASCO Annual Meeting 2015 (29 May–2 June, IL, USA).

Source: Roswell Park Cancer Institute press release

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