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Introduction to Ex Vivo Cancer Models

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Ex Vivo Engineering of the Tumor Microenvironment

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

Abstract

Cancer arises from acquired (and sometimes inherited) genetic changes in cells giving rise to a clonal population of neoplastic cells. However, continued growth of a tumor relies on recruitment and subversion of normal stromal elements [2]. In the cell autonomous view of cancer, a tumor is viewed primarily as a genetic disorder whereby a mutation (or series of mutations or other molecular changes) is sufficient to give rise to the malignant state. Thereafter, signaling transduction pathways become deranged, often in ‘oncogene addicted’ states that promote cell growth. In such states, transcriptional programs are co-opted to promote immortalization, resistance to cell senescence and apoptosis, escape of cell cycle checkpoints, promotion of growth of feeding blood vessels (angiogenesis), and ultimately adoption of an invasive and metastatic phenotype. This ‘reductionist’ view of cancer is in keeping with the original six hallmarks of cancer as detailed by Hanahan and Weinberg in 2000 [1]. This viewpoint is a useful construct and effectively synthesizes decades of groundbreaking research to characterize the impact of oncogenic drivers and tumor suppressor genes in cancer cell biology.

The field of cancer research has largely been guided by a reductionist focus on cancer cells and the genes within them—a focus that has produced an extraordinary body of knowledge. Looking forward in time, we believe that important new inroads will come from regarding tumors as complex tissues in which mutant cancer cells have conscripted and subverted normal cell types to serve as active collaborators in their neoplastic agenda. The interactions between the genetically altered malignant cells and these supporting coconspirators will prove critical to understanding cancer pathogenesis and to the development of novel, effective therapies.—Hanahan and Weinberg, Cell 2000 [1]

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  1. Department of Medical Oncology, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Russell W. Jenkins

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  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Amir R. Aref

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    David Barbie

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Jenkins, R.W. (2017). Introduction to Ex Vivo Cancer Models. In: Aref, A., Barbie, D. (eds) Ex Vivo Engineering of the Tumor Microenvironment. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-45397-2_1

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