Personalized Oncogenomics (POG) Program of British Columbia

Titre officiel

Personalized Oncogenomics (POG) Program of British Columbia: Utilization of Genomic Analysis to Better Understand Tumour Heterogeneity and Evolution

Sommaire:

L’hétérogénéité du génome des cancers oblige les chercheurs à évaluer chacun des cancers afin de leur attribuer le traitement ciblé biologiquement approprié. Les chercheurs auront recours au séquençage complet du génome pour tenter d’identifier les « moteurs » du cancer et les médicaments correspondants pouvant bloquer ces voies.

Description de l'essai

Primary Outcome:

  • Influence of genomic data on clinical decision-making
  • Cataloging of cancer genomes
Carcinogenesis is an immensely complex process such that even within a histologic cancer subtype
  • for example adenocarcinoma of the lung or breast
  • there is significant variability in cancer behaviour and response to therapy. Analyses of individual patients demonstrate unique molecular signatures for every cancer examined. Frequently, multiple different pathways are involved in disease growth and progression and the dominant process varies from person to person and perhaps even within different sites of disease within one person. As well these variations evolve in response to treatment. Recognizing genetic aberrations that promote disease facilitates targeted treatment; this has been demonstrated in several small subgroups of cancers in which specific genetic mutations or translocations have been successfully treated with targeted chemotherapy agents. With many recognized mutations and aberrations, personalized evaluation of the genetic signature encoded in DNA and RNA may provide important diagnostic information and potentially enable directed therapy to the appropriate oncologic pathway thereby providing information to help guide chemotherapy choices Our initial pilot project demonstrated the feasibility of this approach at our institution (with 100 patients). We now know it is possible to identify and consent patients, sequence the genome and transcriptome, analyze and report abnormalities, and identify potential actionable targets in a clinically relevant time frame. The overarching theme of this POG Program is to create a comprehensive cataloguing of somatic cancer mutations and cellular pathway abnormalities that could generate profound insights into genetic patterns that underlie particular cancer phenotypes, and provide valuable prognostic and predictive information. Eligible subjects will have several samples analyzed: a fresh tumour biopsy (typically 5 cores are required), a blood sample for normal comparison and archival tumours when available. Comprehensive DNA and RNA sequencing is performed followed by an in-depth bioinformatic analysis to identify somatic mutations, gene expression changes or other abnormalities that might be cancer "drivers" or provide actionable (diagnostic) or druggable targets. The POG team meets every week to discuss the detailed genomic reports for patients, consider additional validation tests when necessary, and debate research questions. The clinicians (typically 5
  • 10) come to a consensus on what systemic therapies might be appropriate based on these results. Whenever possible subjects are matched to clinical trials.

Voir cet essai sur ClinicalTrials.gov

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