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Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy

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Abstract

The discovery of rare tumor cells with stem cell features first in leukemia and later in solid tumors has emerged as an important area in cancer research. It has been determined that these stem-like tumor cells, termed cancer stem cells, are the primary cellular component within a tumor that drives disease progression and metastasis. In addition to their stem-like ability to self-renew and differentiate, cancer stem cells are also enriched in cells resistant to conventional radiation therapy and to chemotherapy. The immediate implications of this new tumor growth paradigm not only require a re-evaluation of how tumors are initiated, but also on how tumors should be monitored and treated. However, despite the relatively rapid pace of cancer stem cell research in solid tumors such as breast, brain, and colon cancers, similar progress in lung cancer remains hampered in part due to an incomplete understanding of lung epithelial stem cell hierarchy and the complex heterogeneity of the disease. In this review, we provide a critical summary of what is known about the role of normal and malignant lung stem cells in tumor development, the progress in characterizing lung cancer stem cells and the potential for therapeutically targeting pathways of lung cancer stem cell self-renewal.

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Acknowledgements

This publication was supported in part by Grant NNJ05HD36G and NNX09AU95G from the National Aeronautic and Space Administration (NASA). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NASA. We also acknowledge NCI Lung Cancer SPORE P50CA70907.

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Authors and Affiliations

  1. Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    James P. Sullivan & John D. Minna

  2. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    James P. Sullivan, John D. Minna & Jerry W. Shay

  3. Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    John D. Minna

  4. Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    John D. Minna

  5. Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA

    Jerry W. Shay

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  1. James P. Sullivan
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Correspondence to Jerry W. Shay.

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Sullivan, J.P., Minna, J.D. & Shay, J.W. Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy. Cancer Metastasis Rev 29, 61–72 (2010). https://doi.org/10.1007/s10555-010-9216-5

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