domingo, 18 de junio de 2017

Precision Oncology Based on Omics Data: The NCT Heidelberg Experience. - PubMed - NCBI

Precision Oncology Based on Omics Data: The NCT Heidelberg Experience. - PubMed - NCBI

 2017 Jun 9. doi: 10.1002/ijc.30828. [Epub ahead of print]

Precision Oncology Based on Omics Data: The NCT Heidelberg Experience.

Horak P1,2Klink B3,4,5,6Heining C1,2Gröschel S1,2,7,8,9Hutter B10Fröhlich M10Uhrig S10Hübschmann D11,12,13Schlesner M11Eils R11,12Richter D1Pfütze K1,14Geörg C1,14Meißburger B1,14Wolf S15Schulz A15Penzel R16Herpel E16Kirchner M16Lier A16Endris V16Singer S16Schirmacher P9,16Weichert W17,18Stenzinger A9,16Schlenk RF19Schröck E3,4,5,6Brors B9,10von Kalle C1,2,9,14Glimm H1,2,9Fröhling S1,2,9.


Precision oncology implies the ability to predict which patients will likely respond to specific cancer therapies based on increasingly accurate, high-resolution molecular diagnostics as well as the functional and mechanistic understanding of individual tumors. While molecular stratification of patients can be achieved through different means, a promising approach is next-generation sequencing of tumor DNA and RNA, which can reveal genomic alterations that have immediate clinical implications. Furthermore, certain genetic alterations are shared across multiple histologic entities, raising the fundamental question of whether tumors should be treated by molecular profile and not tissue of origin. We here describe MASTER (Molecularly Aided Stratification for Tumor Eradication Research), a clinically applicable platform for prospective, biology-driven stratification of younger adults with advanced-stage cancer across all histologies and patients with rare tumors. We illustrate how a standardized workflow for selection and consenting of patients, sample processing, whole-exome/genome and RNA sequencing, bioinformatic analysis, rigorous validation of potentially actionable findings, and data evaluation by a dedicated molecular tumor board enables categorization of patients into different intervention baskets and formulation of evidence-based recommendations for clinical management. Critical next steps will be to increase the number of patients that can be offered comprehensive molecular analysis through collaborations and partnering, to explore ways in which additional technologies can aid in patient stratification and individualization of treatment, to stimulate clinically guided exploratory research projects, and to gradually move away from assessing the therapeutic activity of targeted interventions on a case-by-case basis towards controlled clinical trials of genomics-guided treatments. This article is protected by copyright. All rights reserved.


Clinical Trial Design; Next-Generation Sequencing; Personalized Medicine; Precision Oncology; Whole-exome Sequencing


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