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Molecular Diagnostics and Genomic Profiling in Individualized Therapies of Gastrointestinal Cancers

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Textbook of Gastrointestinal Oncology

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Abstract

The human genome project, completed in 2003, provided the first reference map for the whole human genome and stimulated enormous advances in DNA sequencing technology. These technologies allowed for an increasingly detailed description of the molecular landscape of cancer, including gastrointestinal (GI) cancers. Widespread availability of next-generation sequencing (NGS) has led to extensive use of this method in the clinic and at the individual patient level. In-depth molecular knowledge can offer unique opportunities for exploring cancer pathogenesis, germline mutation inheritance, and early cancer detection. NGS has the capability to identify unique features of an individual’s cancer, hence the potential for personalizing diagnostic and therapeutic strategies. Despite the potential benefits, integration of cancer genomics care delivery, especially in the area of solid cancer treatments, including gastrointestinal (GI) malignancies, has been challenging. In rare cases, cancers are dependent in their survival on one prominent driver mutation or genetic aberration, and pharmacological targeting of these driver mutation/aberrations can effectively control that cancer type. However, in most solid tumors, multiple mutations/genetic alterations are present and are undergoing dynamic clonal evolution, making it difficult to identify key mutations and prioritize treatment based on them. Temporal and spatial heterogeneity of the tumor, lack of availability of adequate tissue, limited access to clinical trials, and off-label treatments are all among challenges faced while utilizing clinical genomics in clinical practice. Nevertheless, recent progress in targeting molecular features, such as mismatch repair deficiency, or strong oncogenic genomic events, such as NTRK fusions, demonstrate the promising potential of this approach.

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Authors and Affiliations

  1. Department of Hematology Oncology, Karmanos Cancer Institute, Detroit, MI, USA

    Mandana Kamgar

  2. Caris Life Sciences, Phoenix, AZ, USA

    W. Michael Korn

  3. Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA, USA

    W. Michael Korn

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  1. Mandana Kamgar
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  1. Department of Medical Oncology, Hacettepe University Institute of Cancer, Sihhiye, Ankara, Turkey

    Suayib Yalcin

  2. Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Philip A. Philip

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Kamgar, M., Korn, W.M. (2019). Molecular Diagnostics and Genomic Profiling in Individualized Therapies of Gastrointestinal Cancers. In: Yalcin, S., Philip, P. (eds) Textbook of Gastrointestinal Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-18890-0_34

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