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Review
. 2014 Nov 20:6:423-32.
doi: 10.2147/CLEP.S69718. eCollection 2014.

Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

Puey Ling Chia  1 , Paul Mitchell  1 , Alexander Dobrovic  2 , Thomas John  3
Affiliations
Review

Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

Puey Ling Chia et al. Clin Epidemiol. .

Abstract

Improved understanding of molecular drivers of carcinogenesis has led to significant progress in the management of lung cancer. Patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangements constitute about 4%-5% of all NSCLC patients. ALK+ NSCLC cells respond well to small molecule ALK inhibitors such as crizotinib; however, resistance invariably develops after several months of treatment. There are now several newer ALK inhibitors, with the next generation of agents targeting resistance mutations. In this review, we will discuss the prevalence and clinical characteristics of ALK+ lung cancer, current treatment options, and future directions in the management of this subset of NSCLC patients.

Keywords: anaplastic lymphoma kinase (ALK); gene rearrangements; kinase inhibitors; lung adenocarcinoma; lung cancer.

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Figures

Figure 1
Figure 1
Incidence and variety of oncogenic drivers in lung adenocarcinoma. Note: Data from Kris et al. Abbreviations: ALK, anaplastic lymphoma kinase; BRAF, V-raf murine sarcoma viral oncogene homolog B1; EGFR, epidermal growth factor receptor; EML, echinoderm microtubule-associated protein-like 4; HER2, human epidermal growth factor receptor 2; KRAS, Kirsten rat sarcoma viral oncogene; MET, mesenchyme to epithelial transition.
Figure 2
Figure 2
Illustration of EML4-ALK fusion oncogene in non-small-cell lung cancer and the detection by FISH. Notes: The red and green signals are usually next to each other on chromosome 2; however, when the ALK translocation is present, the red and green probes separate and are seen as the classic FISH break-apart signal. ALK FISH image courtesy of Dr Adrienne Morey, St Vincent’s Hospital, Sydney. Abbreviations: ALK, anaplastic lymphoma kinase; EML, echinoderm microtubule-associated protein-like 4; FISH, fluorescence in situ hybridization.
Figure 3
Figure 3
Potential mechanisms of resistance in ALK+ NSCLC. Abbreviations: NSCLC, non-small-cell lung cancer; ALK, anaplastic lymphoma kinase.
See this image and copyright information in PMC

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