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

ABSTRACT:

In this study, we used NGS to identify somatic events in advanced stage cancer patients to demonstrate the feasibility for using this approach to improve patient treatment.

PROVIDER: phs000657.v1.p1 | EGA |

REPOSITORIES: EGA

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A pilot study using next generation sequencing in advanced cancers: feasibility and challenges

Project description:A pilot study using next generation sequencing in advanced cancers: feasibility and challenges

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A pilot study using next-generation sequencing in advanced cancers: feasibility and challenges.

Project description: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.

| S-EPMC3813699 | biostudies-literature

NGS in Advanced Cancers

Project description:<p>In this study, we used NGS to identify somatic events in advanced stage cancer patients to demonstrate the feasibility for using this approach to improve patient treatment.</p>

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Detect Microsatellite Instability Status in Blood Sample of Advanced Colorectal Cancer Patients by Next-Generation Sequencing

Project description:The method to analyze the microsatellite instability (MSI) status by next-generation sequencing (NGS) has been established to assess the deficiency of DNA mismatch repair (MMR) system. The aim of our study is to evaluate the feasibility and reliability of this NGS method by testing the circulating tumor DNA (ctDNA) in blood sample of advanced colorectal cancer patients. If the result is positive, the MSI status could be easily learned without the acquisition of tissue samples.

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Project description:This is a prospective, single-center, clinical study.This study is to evaluate the feasibility of genetic susceptibility screening based on the detection of tumor tissue mutations by a NGS panel.

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Next generation sequencing of advanced non-castrate prostate cancer treated with docetaxel chemotherapy

Project description:Early chemotherapy for advanced/metastatic non-castration resistant prostate cancer (PCa) may improve overall patient survival. We studied the safety, tolerability and early efficacy of up-front docetaxel chemotherapy and androgen deprivation therapy (ADT) versus ADT alone for patients with newly-diagnosed advanced/metastatic PCa. As proof of concept, we undertook in vivo gene expression profiling by next generation RNA sequencing (RNA-Seq). Tumour biposies from 6 patients were taken before and after treatment with combined ADT and docetaxcel for 6 weeks

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Next-generation sequencing of immunoglobulin gene rearrangements for clonality assessment: a technical feasibility study by EuroClonality-NGS

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Technical and implementation issues in using next-generation sequencing of cancers in clinical practice.

Project description:Next-generation sequencing (NGS) of cancer genomes promises to revolutionise oncology, with the ability to design and use targeted drugs, to predict outcome and response, and to classify tumours. It is continually becoming cheaper, faster and more reliable, with the capability to identify rare yet clinically important somatic mutations. Technical challenges include sequencing samples of low quality and/or quantity, reliable identification of structural and copy number variation, and assessment of intratumour heterogeneity. Once these problems are overcome, the use of the data to guide clinical decision making is not straightforward, and there is a risk of premature use of molecular changes to guide patient management in the absence of supporting evidence. Paradoxically, NGS may simply move the bottleneck of personalised medicine from data acquisition to the identification of reliable biomarkers. Standardised cancer NGS data collection on an international scale would be a significant step towards optimising patient care.

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Project description: Not available

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Next-generation immunotherapies for brain metastatic cancers.

Project description:Patients with extracranial tumors, like lung, breast, and skin cancers, often develop brain metastases (BM) during the course of their diseases and BM commonly represent the terminal stage of cancer progression. Recent insights in the immune biology of BM and the increasing focus of immunotherapy as a therapeutic option for cancer has prompted testing of promising biological immunotherapies, including immune cell-targeting, virotherapy, vaccines, and different cell-based therapies. Here, we review the pathobiology of BM progression and evaluate the potential of next-generation immunotherapies for BM tumors. We also provide future perspectives on the development and implementation of such therapies for brain metastatic cancer patients.

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