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PurposeNew 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 designIn 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.ResultsWGS 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.ConclusionWhile 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.

Original publication

DOI

10.1371/journal.pone.0076438

Type

Journal article

Journal

PloS one

Publication Date

01/2013

Volume

8

Addresses

Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare (VGPCC), Scottsdale, Arizona, United States of America ; The Translational Genomics Research Institute, Phoenix, Arizona, United States of America.

Keywords

Humans, Neoplasms, Neoplasm Metastasis, Fluorodeoxyglucose F18, Positron-Emission Tomography, Tomography, X-Ray Computed, Neoplasm Staging, Pilot Projects, Gene Expression Profiling, Adult, Aged, Middle Aged, Female, Male, Young Adult, DNA Copy Number Variations, High-Throughput Nucleotide Sequencing, Transcriptome