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Lung Cancer pp 331–393Cite as

Lung Cancer Resistance to Chemotherapy

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Part of the book series: Current Clinical Oncology ((CCO))

Abstract

Metastatic lung cancer remains incurable by chemotherapy. Several factors contribute to resistance to chemotherapy, including many factors that are adaptations of systems that evolved to protect normal cells from a hostile environment. Tumor cell characteristics, tumor cell interactions with extracellular matrix and stromal cells, and tumor physical characteristics all contribute to resistance. Resistance may arise from gene upregulation or downregulation as a downstream consequence of the oncogene mutations or tumor suppressor gene deletions that underlie tumorigenesis or may also arise due to tumor hypoxia or due to exposure to therapy. Host gene polymorphisms may alter resistance by determining the half-life or enzymatic activity of upregulated resistance factors. Resistance may arise from decreased drug delivery to tumor, impact of extracellular pH on drug uptake, altered drug uptake transporters or cell membrane characteristics, increased drug efflux or detoxification, decreased drug binding, altered drug targets, increased DNA repair, decreased proapoptotic factors, increased antiapoptotic factors, altered cell cycling or mitotic checkpoints, or altered transcription factors. This diversity of resistance mechanisms magnifies the challenges facing us in predicting patient prognosis and in overcoming resistance.

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  1. Department of Thoracic/Head & Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    David J. Stewart

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  1. M. D. Anderson Cancer Center, University of Texas, Holcombe Blvd. 1515, Houston, 77030, U.S.A.

    David J. Stewart

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Stewart, D.J. (2010). Lung Cancer Resistance to Chemotherapy. In: Stewart, D. (eds) Lung Cancer. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-524-8_15

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