The potential for crizotinib in non-small cell lung cancer: a perspective review - PubMed (original) (raw)

The potential for crizotinib in non-small cell lung cancer: a perspective review

Yung-Jue Bang. Ther Adv Med Oncol. 2011 Nov.

Abstract

Tyrosine kinases have a crucial role as key regulators of signaling pathways that influence cell differentiation and growth. Dysregulation of tyrosine kinase-mediated signaling is understood to be an important oncogenic driver. Genetic rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) gene occur in non-small cell lung cancer (NSCLC), anaplastic large cell lymphomoas, inflammatory myofibroblastic tumors, and other cancers. Cells with abnormal ALK signaling are sensitive to ALK inhibitors such as crizotinib. This review will highlight the discovery of the fusion between echinoderm microtubule-associated protein-like 4 (EML4) and ALK as an oncogenic driver, recognition of other ALK gene rearrangements in NSCLC, and the confirmation that crizotinib is an effective treatment for patients with ALK-positive NSCLC. Work is underway to further define the role for crizotinib in the treatment of ALK-positive lung cancer and other cancers and to investigate the molecular mechanisms for resistance to ALK inhibition with crizotinib.

Keywords: anaplastic lymphoma kinase; carcinoma; crizotinib; non-small cell lung cancer; tyrosine kinase inhibitor.

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Figures

Figure 1.

Figure 1.

Crizotinib in the anaplastic lymphoma kinase ATP binding pocket [Camidge et al. 2010a].

Figure 2.

Figure 2.

Waterfall plot of best percentage change from baseline in target lesions by patient in patients with anaplastic lymphoma kinase (ALK)_-_positive non-small cell lung cancer who received crizotinib (excluding those with early death and indeterminate or unavailable response from the 105 evaluable patients; August 2010) [Camidge et al. 2010a]. CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.

Figure 3.

Figure 3.

Time to response with crizotinib for responding patients (n = 59 of 105 evaluable patients; August 2010) [Solomon et al. 2010].

Figure 4.

Figure 4.

Progression-free survival (PFS) following treatment with crizotinib (August 2010; N = 113) [Camidge et al. 2010a]. CI, confidence interval.

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