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Characteristics of the Metastatic Phenotype

The Melanoma Experience

  • Chapter
Cancer Drug Resistance

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 1610 Accesses

Abstract

Malignant progression and tumor metastasis is a complex process enabled by various molecular changes occurring in a subpopulation of tumor cells. The metastatic phenotype is associated with the cellular capacity for uncontrolled growth, resistance to apoptosis, high invasive potential, and effective neoangiogenesis. Whereas the contribution of genetic alterations to the metastatic dissemination is not yet clear, because both primary and metastatic tumors often have similar patterns of genetic mutations, the majority of the changes contributing to the metastatic phenotype are controlled epige-netically. In melanoma, the progression toward malignant disease and acquisition of the metastatic phenotype involves loss of activator protein 2 and gain in expression of activating transcription factor 1/cyclic adenosine monophosphate-responsive element-binding protein family transcription factors. Together with upregulation of activating transcription factor 2, Snail, nuclear factor-?B and other transcription factors, this results in deregulation of the expression of cellular adhesion molecules, matrix-degrading enzymes, as well as other factors that enable a complex interaction of tumor cells with extracellular milieu and other cells during malignant progression and metastatic dissemination. Furthermore, because of the need to survive mechanical and immunological challenges, and changing nutritional environment during the dissemination process, metastatic cells are permanently selected for the superior survival capacity. As a result, metastatic cells are commonly characterized by their increased resistance to the chemotherapeutic treatment when compared to primary tumors. Here, we discuss some of the potential mechanisms contributing to drug resistance in melanoma.

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  1. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX

    Vladislava O. Melnikova PhD

  2. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas

    Menashe Bar-Eli PhD

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  1. Vladislava O. Melnikova PhD
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  1. Genzyme Corporation, Framingham, MA

    Beverly A. Teicher PhD

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Melnikova, V.O., Bar-Eli, M. (2006). Characteristics of the Metastatic Phenotype. In: Teicher, B.A. (eds) Cancer Drug Resistance. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-035-5_10

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