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Molecular Pathology and Diagnostics of Non-small Cell Lung Carcinoma

  • Brian Quigley
  • Steve Ducker
  • Farah KhalilEmail author
Chapter
Part of the Cancer Growth and Progression book series (CAGP, volume 16)

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.

Keywords

Cancer Lung Carcinoma Non-small cell Molecular Smoker Squamous cell carcinoma Adenocarcinoma EGFR KRAS ALK FISH ERCC1 RRM1 

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

Notes

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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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Pathology and Cell BiologyUniversity of South FloridaTampaUSA
  2. 2.Moffitt Cancer Center and Research InstituteTampaUSA

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