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Molecular Pathology and Diagnostics of Non-small Cell Lung Carcinoma

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Book cover Molecular Pathology and Diagnostics of Cancer

Part of the book series: Cancer Growth and Progression ((CAGP,volume 16))

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Abstract

Of all the molecular alterations that may have predictive value in non-small cell lung cancer (NSCLC), testing for EGFR mutations is usually the first step in determining course of adjuvant therapy. Activation of EGFR mutations, and perhaps amplification, predicts the response of NSCLC to tyrosine kinase inhibitors (TKIs). The presence of activating KRAS mutations predicts resistance to TKI therapy, but the value of this test is questionable in NSCLC given that the coexistence of both EGFR and KRAS mutations in the same patient is extremely rare and the presence of a KRAS mutation may not have much different significance than the absence of an EGFR mutation. In patients who are considered for gemcitabine therapy, measurement of ribonucleotide reductase subunit 1 (RRM1) expression levels may help predict which patients are less likely to respond, as higher levels of RRM1 have been shown to overcome the anti-metabolite of this drug. Similarly, in patients being considered for platinum-based therapy, determination of excision-repair cross complementing-1 protein (ERCC1) expression level may help predict which patients are less likely to respond, given that ERCC1 repairs platinum-induced DNA damage. The use of these predictive factors ideally will help target therapy to individual tumors to achieve the best chance for long-term survival and to avoid side effects from medications that are unlikely to have any effect. Further studies will continue to refine testing and treatment algorithms.

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Abbreviations

ALK:

Anaplastic lymphoma kinase

ARMS:

Amplification refractory mutation system analysis

dNTP:

Deoxyribonucleoside triphosphate

EGFR:

Epidermal growth factor receptor

ELM4:

Echinoderm microtubule-associated protein-like 4

ERCC1:

Excision-repair cross complementing-1 protein

ERK:

Extracellular signal-regulated kinase

FISH:

Fluorescence in-situ hybridization

IHC:

Immunohistochemistry

LOH 3p:

Loss of heterozygosity of 3p

MASI:

Mutant allele-specific imbalance

MEK:

MAPK/ERK kinase

MRP:

Multidrug resistance protein

NSCLC:

Non-small cell lung cancer

PI3K:

Phosphoinositide 3-kinase

PTEN:

Phosphatase and tensin homolog

RRM1:

Ribonucleotide reductase subunit 1

SNP:

Single-nucleotide polymorphisms

TKI:

Tyrosine kinase inhibitors

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Acknowledgements

We thank Dr. Jhanelle Gray, Assistant Member, Department of Thoracic Oncology and Experimental Therapeutics Program at Moffitt Cancer Center, for her help with the EGFR Summary.

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Authors and Affiliations

  1. Department of Pathology and Cell Biology, University of South Florida, Tampa, FL, USA

    Brian Quigley M.D., Steve Ducker M.D. & Farah Khalil M.D.

  2. Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Brian Quigley M.D., Steve Ducker M.D. & Farah Khalil M.D.

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  1. Brian Quigley M.D.
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  2. Steve Ducker M.D.
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  3. Farah Khalil M.D.
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Correspondence to Farah Khalil M.D. .

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  1. Anatomic Pathology, University of South Florida, Moffitt Cancer Center, Tampa, Florida, USA

    Domenico Coppola

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Quigley, B., Ducker, S., Khalil, F. (2014). Molecular Pathology and Diagnostics of Non-small Cell Lung Carcinoma. In: Coppola, D. (eds) Molecular Pathology and Diagnostics of Cancer. Cancer Growth and Progression, vol 16. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7192-5_4

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