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

Glen J. Weiss mail,
Winnie S. Liang,
Michael J. Demeure,
Jeff A. Kiefer,
Galen Hostetter,
Tyler Izatt,
Shripad Sinari,
Alexis Christoforides,
Jessica Aldrich,
Ahmet Kurdoglu,
Lori Phillips,
Hollie Benson,
Rebecca Reiman,
[ ... ],
David W. Craig equal contributor
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Abstract

Purpose

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.

Experimental Design

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.

Results

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.

Conclusion

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.

Citation: Weiss GJ, Liang WS, Demeure MJ, Kiefer JA, Hostetter G, et al. (2013) A Pilot Study Using Next-Generation Sequencing in Advanced Cancers: Feasibility and Challenges. PLoS ONE 8(10): e76438. doi:10.1371/journal.pone.0076438
Editor: Patrick Tan, Duke-National University of Singapore Graduate Medical School, Singapore
Received: April 24, 2013; Accepted: August 23, 2013; Published: October 30, 2013
Copyright: © 2013 Weiss et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Funding was provided by the National Foundation of Cancer Research (www.nfcr.org) and the Lee T. Hanley Fund for Pancreatic Cancer Research (http://www.tgenfoundation.org/netcommunity/page.aspx?pid=1196). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.