Journal Article

A Pilot Study Using Next-Generation Sequencing in Advanced Cancers: Feasibility and Challenges

Christoforides, Alexis, Reiman, Rebecca, Craig, David W., Baker, Angela, Benson, Hollie, Hostetter, Galen, Von Hoff, Daniel D., Aldrich, Jessica, Carpten, John D., Kiefer, Jeff A., Liang, Winnie S., Phillips, Lori, Marsh, Vickie, Demeure, Michael J., Kurdoglu, Ahmet, Izatt, Tyler, Weiss, Glen J., Sinari, Shripad

2013

Overview

New anticancer agents that target a single cell surface receptor, up-regulated or amplified gene product, or mutated gene, have met with some success in treating advanced cancers. However, patients' tumors still eventually progress on these therapies. If it were possible to identify a larger number of targetable vulnerabilities in an individual's tumor, multiple targets could be exploited with the use of specific therapeutic agents, thus possibly giving the patient viable therapeutic alternatives. In this exploratory study, we used next-generation sequencing technologies (NGS) including whole genome sequencing (WGS), and where feasible, whole transcriptome sequencing (WTS) to identify genomic events and associated expression changes in advanced cancer patients. WGS on paired tumor and normal samples from nine advanced cancer patients and WTS on six of these patients' tumors was completed. One patient's treatment was based on targets and pathways identified by NGS and the patient had a short-lived PET/CT response with a significant reduction in his tumor-related pain. To design treatment plans based on information garnered from NGS, several challenges were encountered: NGS reporting delays, communication of results to out-of-state participants and their treating oncologists, and chain of custody handling for fresh biopsy samples for Clinical Laboratory Improvement Amendments (CLIA) target validation. While the initial effort was a slower process than anticipated due to a variety of issues, we demonstrate the feasibility of using NGS in advanced cancer patients so that treatments for patients with progressing tumors may be improved.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Anticancer properties / Antitumor agents / Biopsy / Breast cancer / Cancer / Cancer therapies / Cell surface / Chemical compounds / Clinical trials / Deoxyribonucleic acid / DNA / DNA Copy Number Variations / Drug development / Experimental design / Feasibility studies / Female / Fluorodeoxyglucose F18 / Gene expression / Gene Expression Profiling / Gene sequencing / Genomes / Genomics / High-Throughput Nucleotide Sequencing / Humans / Male / Metastasis / Middle Aged / Neoplasm Metastasis / Neoplasm Staging / Neoplasms - diagnosis / Neoplasms - genetics / Neoplasms - pathology / Neoplasms - therapy / Pain / Patients / Pharmacology / Pilot Projects / Positron-Emission Tomography / Studies / Supply chains / Target recognition / Tomography, X-Ray Computed / Transcriptome / Tumors / Young Adult