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ASCO 2015: Biomarker Analysis Reveals Several Potential Treatment Targets in Subtype of Anal Cancer

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Key Points

  • Immunohistochemistry overexpression was found in several genes, including MRP1, EGFR, TOPO1, MGMT, and PTEN.
  • High mutation rates were seen in biomarkers associated with the PIK3CA/Akt pathway (PIK3CA, FBXW7, PTEN and Akt1).
  • PIK3CA exon 9 mutations were detected in 75% of all PIK3CA mutations.

Squamous cell anal carcinomas are rare, representing only about 2% of gastrointestinal cancer diagnoses. These cancers, which are associated with the human papillomavirus (HPV), sometimes prove very difficult to treat, recurring or developing metastases following standard treatment. Seeking to identify new targets and therapeutic options for this disease, a multi-institutional team led by Patrick Boland, MD, of Roswell Park Cancer Institute conducted a multiplatform biomarker analysis in conjunction with Caris Life Sciences that revealed several actionable targets. Their findings were presented June 1 at the 2015 ASCO Annual Meeting in Chicago (Abstract 3519).

The researchers analyzed 212 tumor samples using three types of genetic profiling: gene sequencing (Sanger or next-generation sequencing), protein expression (immunohistochemistry [IHC]), and gene amplification (CISH or FISH assays). For 80.2% of the samples, tissue from a metastatic site was also analyzed.

Analysis Findings

The team found evidence of significant IHC overexpression in several genes: MRP1, in 97.6% of the analyzed samples; EGFR, in 89.7%; TOPO1, in 68.3%; MGMT, in 67.2%; and PTEN, in 46.9%. EGFR and HER2 were amplified in 7.4% and 1.8% of the cases, respectively. Additionally, high mutation rates were seen 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—anti-EGFR agents or newer pan-HER inhibitors,” said Dr. Boland, an Assistant Professor of Oncology in the Department of Medicine at Roswell Park. “Additionally, our results suggest that this approach may be similarly effective in identifying targets in other tumors of viral origin.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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