Feasibility of real time next generation sequencing of cancer genes linked to drug response: Results from a clinical trial

  title={Feasibility of real time next generation sequencing of cancer genes linked to drug response: Results from a clinical trial},
  author={Ben Tran and Andrew M. K. Brown and Philippe B{\'e}dard and Eric Winquist and Glenwood D Goss and Sebastien Hotte and Stephen A. Welch and Hal W. Hirte and Tong Zhang and Lincoln D. Stein and Vincent Ferretti and Stuart N. Watt and Wei Jiao and Karen Ng and Sangeet Ghai and Patricia A. Shaw and Teresa Petrocelli and Thomas J. Hudson and Benjamin G. Neel and Nicole Onetto and Lillian L. Siu and John D. McPherson and Suzanne Kamel‐Reid and Janet E. Dancey},
  journal={International Journal of Cancer},
The successes of targeted drugs with companion predictive biomarkers and the technological advances in gene sequencing have generated enthusiasm for evaluating personalized cancer medicine strategies using genomic profiling. We assessed the feasibility of incorporating real‐time analysis of somatic mutations within exons of 19 genes into patient management. Blood, tumor biopsy and archived tumor samples were collected from 50 patients recruited from four cancer centers. Samples were analyzed… 

Clinical tumor sequencing: opportunities and challenges for precision cancer medicine.

Although whole-genome sequencing offers the most complete strategy for tumor analysis, its present utility in clinical care is limited, and targeted gene capture panels are more commonly employed by academic institutions and commercial vendors for clinical grade cancer genomic testing to assess molecular eligibility for matching therapies.

Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers

Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets.

Towards a Next-Generation Sequencing Diagnostic Service for Tumour Genotyping: A Comparison of Panels and Platforms

The results indicate that the panels enable accurate variant detection despite sequencing from FFPE DNA, and allow mutation detection of core cancer genes including KRAS, BRAF, and EGFR.

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Targeted high-coverage NGS panels are a highly feasible single-centre technology well-suited to cross-platform validation, enrichment of trials with molecularly defined populations and hypothesis testing early in drug development.

Implementation of a Multicenter Biobanking Collaboration for Next-Generation Sequencing-Based Biomarker Discovery Based on Fresh Frozen Pretreatment Tumor Tissue Biopsies.

It is safe to perform image-guided biopsy procedures to obtain fresh frozen tumor samples and that it is feasible to use these biopsies for biomarker discovery purposes in a Dutch multicenter collaboration, and results indicate that the way is paved for consortia to prospectively collect freshrozen tumor tissue.

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer

The findings demonstrate that targeted NGS using cfDNA is a feasible approach for rapid and accurate identification of actionable mutations in patients with advanced NSCLC, and may provide a safe and robust alternative approach to tissue biopsy.

Testing personalized medicine: patient and physician expectations of next-generation genomic sequencing in late-stage cancer care

The need for information and decision tools to support physicians in communicating realistic prospects of benefit and for cautious approaches to the generation of incidental genetic information is suggested.

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In the samples analyzed, PCDx significantly outperformed F1 in TAT, and had statistically significant higher clinically relevant actionable targets categorized as CA.

Biology of Human Tumors Noninvasive Diagnosis of Actionable Mutations by Deep Sequencing of Circulating Free DNA in Lung Cancer from Never-Smokers : A Proof-of-Concept Study

Next-generation sequencing on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations demonstrate the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of arange of tumor biomarkers in patients with metastatic lung cancer.



Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

The implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting and demonstrates the clinical feasibility of high-throughput mutation profiling to query a large panel of “actionable” cancer gene mutations is reported.

Routine Multiplex Mutational Profiling of Melanomas Enables Enrollment in Genotype-Driven Therapeutic Trials

Development, validation, and implementation of an assay designed to simultaneously detect 43 common somatic point mutations in 6 genes potentially relevant to existing and emerging targeted therapies specifically in melanoma are reported on.

Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study

The mutations present in advanced cancers can be identified by integrative high-throughput sequencing to enable biomarker-driven clinical trials and, ultimately, treatment and the authors tested this approach by extensively characterizing cancers in several patients and then convening a Sequencing Tumor Board of experts to determine the appropriate treatment.

Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers.

It is possible to identify molecular targets in patients' tumors from nine different centers across the United States and in 27% of patients, the MP approach resulted in a longer PFS on an MP-suggested regimen than on the regimen on which the patient had just experienced progression.

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Cancer genomics: technology, discovery, and translation.

  • B. TranJ. Dancey L. Siu
  • Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2012
The technology underlying cancer genomics is highlighted and the early results of genome sequencing and the challenges met in the discovery of new genetic aberrations are examined.

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It is suggested that late switch in KRAS mutational status could occur more frequently than currently recognized and account for acquired resistance to anti-EGFR therapies.

PIK3CA mutations rarely demonstrate genotypic intratumoral heterogeneity and are selected for in breast cancer progression

This data is clinically important, particularly, for the design of therapies targeting the PI3K/AKT pathway, as it offers confidence that the detection of PIK3CA mutations in the invasive primary tumor will accurately reflect breast cancer biology.