Abstract
The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.
Highlights
The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities
The discovery that the echinoderm microtubuleassociated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion protein was a potent oncogenic driver in NSCLC rapidly fueled the development of the multi-targeted TKI crizotinib, and accelerated its FDA approval for the treatment of patients with advanced ALK -positive NSCLC
Two studies have since shown an overall response rates (ORR) of 60% and a median progression free survival (PFS) of 8–9 months in ALK positive NSCLC patients receiving crizotinib [10]
Summary
The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. To EGFR mutations, the ALK -gene rearrangement defines a unique molecular subset in 3–7% of NSCLC patients [6]. The clinical characteristics of NSCLC patients that are positive for EML4-ALK variants are similar to those of who harbor activating mutations in the EGFR gene: both groups of patients tend to manifest an adenocarcinoma histological subtype and to be non or light smokers [9].
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