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Review
. 2016:35:e585-93.
doi: 10.1200/EDBK_158808.

Tumor Heterogeneity and Therapeutic Resistance

Christine M Lovly  1 , April K S Salama  1 , Ravi Salgia  1
Affiliations
Review

Tumor Heterogeneity and Therapeutic Resistance

Christine M Lovly et al. Am Soc Clin Oncol Educ Book. 2016.

Abstract

The rapidly changing landscape of oncology has brought new light, and with it, new challenges to optimizing therapeutic strategies for patients. Although the concept of patient heterogeneity is well known to any practicing clinician, a more detailed understanding of the biologic changes that underscore the clinical picture is beginning to emerge. Thus, tumor heterogeneity has come to encompass more than just the clinical picture and can represent both intratumor and intertumor differences. Within the fields of thoracic oncology and melanoma, the discovery of key molecular drivers has resulted in landmark breakthroughs in therapy. However, the complexities of tumor genetics and the interaction within the environment continue to drive the search for better therapies. Ongoing challenges include the accurate and timely assessment of genetic changes as well as the development of resistance and the resultant compensatory mechanisms. Novel technologies, including commercially available next-generation sequencing, have allowed for a greater breadth and depth of information to be gained from a single pathologic specimen, and it is now being incorporated into routine clinical practice. Translational advances have subsequently provided valuable insight into mechanisms of resistance, with the development of novel treatment strategies. Future work will focus on novel diagnostic techniques and adaptive mechanisms that can ultimately drive the development of the next generation of cancer therapy.

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Conflict of interest statement

Disclosures of potential conflicts of interest provided by the authors are available with the online article at asco.org/edbook.

Figures

FIGURE 1.
FIGURE 1.. Intertumor and Intratumor Heterogeneity
Intertumor heterogeneity results from variability across different tumors from different individuals, even with the same histopathologic diagnosis. Intratumor heterogeneity results from variability within an individual tumor. Subpopulations exist within a given tumor, as represented by the different colored cells (red, blue, and gray) shown within the tumor. These subpopulations, often referred to as tumor clones, may differ in cell morphology, genetic makeup, metabolism, proliferation rate, and, ultimately, response to therapy.
FIGURE 2.
FIGURE 2.. Overview of the Timeline From Diagnosis to the Development of Metastatic Disease for a Patient With Lung Cancer Harboring an ALK Translocation
FIGURE 3.
FIGURE 3.. Overview of the Timeline From Diagnosis to the Development of Metastatic Disease for a Patient With Lung Cancer With a Number of Genetic Alterations
FIGURE 4.
FIGURE 4.. Overview of the Timeline From Diagnosis to the Development of Metastatic Disease for a Patient With Metastatic Melanoma Harboring a MEKK57N Mutation
See this image and copyright information in PMC

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References

    1. Osler W On the educational value of the medical society. Yale Medical Journal. 1903;9:325.
    1. Hölzel M, Bovier A, Tüting T. Plasticity of tumour and immune cells: a source of heterogeneity and a cause for therapy resistance? Nat Rev Cancer. 2013;13:365–376. - PubMed
    1. Michor F, Polyak K. The origins and implications of intratumor heterogeneity. Cancer Prev Res (Phila). 2010;3:1361–1364. - PMC - PubMed
    1. Welch DR. Tumor heterogeneity-A ‘contemporary concept’ founded on historical insights and predictions. Cancer Res. 2016;76:4–6. - PMC - PubMed
    1. Zellmer VR, Zhang S. Evolving concepts of tumor heterogeneity. Cell Biosci. 2014;4:69. - PMC - PubMed

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