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

Roswell Park research on rare HPV-associated malignancy to be presented at ASCO 2015
Friday, May 29, 2015

BUFFALO, N.Y. — While squamous cell anal carcinomas are rare, representing only about 2% of digestive-system 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 (RPCI) conducted a multiplatform biomarker analysis in conjunction with Caris Life Sciences that revealed several actionable targets.

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

The team found evidence of significant IHC 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. 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, for instance anti-EGFR agents or newer pan-HER inhibitors,” says Dr. Boland, an Assistant Professor of Oncology in the Department of Medicine at Roswell Park and the study’s first and presenting author. “Additionally, our results suggest that this approach may also be similarly effective in identifying targets in other tumors of viral origin.”

The study, “Comprehensive multiplatform biomarker analysis of 212 anal squamous cell carcinomas,” is abstract 3519 and will be presented on board no. 11 during the Gastrointestinal (Colorectal) Cancer poster session Monday, June 1, from 8 a.m. to 11:30 a.m. CDT in McCormick Place, S Hall A, and will also be featured in a poster discussion session later that day, from 1:15 p.m. to 2:30 p.m. CDT in McCormick Place, E Hall D1.

Founded in 1964, ASCO is the world’s leading professional organization representing physicians who care for people with cancer. ASCO 2015 will be held in McCormick Place, Chicago, Ill., from May 29 to June 2, bringing together some 30,000 oncology professionals from around the world.

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The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org. Follow Roswell Park on Facebook and Twitter.

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