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A pilot study using next-generation sequencing in advanced cancers: feasibility and challenges
Glen J Weiss1, Winnie S Liang, Michael J Demeure
1Virginia 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.
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.
Insights
Next-generation sequencing (NGS) can identify multiple tumor vulnerabilities in advanced cancer patients. This approach shows feasibility for improving treatments, despite initial logistical challenges.
Area of Science:
- Genomics and Oncology
- Translational Cancer Research
Background:
- Targeted therapies for advanced cancers show limited success, with eventual tumor progression.
- Identifying multiple tumor vulnerabilities could offer alternative therapeutic strategies.
Purpose of the Study:
- To explore the feasibility of using next-generation sequencing (NGS) to identify genomic alterations and expression changes in advanced cancer.
- To assess the potential of NGS-guided treatment for patients with progressing tumors.
Main Methods:
- Employed whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) on tumor and normal samples from advanced cancer patients.
- Investigated genomic events and associated gene expression changes.
Main Results:
- Completed WGS on nine patients and WTS on six patients.
- One patient receiving NGS-guided treatment showed a temporary PET/CT response and pain reduction.
- Identified challenges including reporting delays, communication issues, and sample handling for Clinical Laboratory Improvement Amendments (CLIA) validation.
Conclusions:
- Demonstrated the feasibility of utilizing NGS in advanced cancer patients.
- Despite initial delays and logistical hurdles, NGS offers a pathway to potentially improve treatments for progressing cancers.
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