Expanded Circulating Tumor Cells from a Patient with ALK-Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable Drug Sensitivity Testing: A Case Study.
Increasing knowledge of molecular aberrations in lung cancer, specifically the discovery of two driver genes in pharmacologically targetable tyrosine kinases involved in growth factor receptor signalling, epidermal growth factor receptor and anaplastic lymphoma kinase, has been of major therapeutic and prognostic importance.
Data from previous studies on the histomorphology of ALK-rearranged lung cancer are inconsistent, and the specific histologic parameters that characterize this subset and how accurately such parameters predict underlying ALK abnormality remain uncertain.
Anaplastic lymphoma kinase 5A4 immunohistochemistry as a diagnostic assay in lung cancer: A Canadian reference testing center's results in population-based reflex testing.
Similar levels of drug sensitivity were displayed by the three most common ALK fusion proteins in lung cancer (EML4-ALK variants E13;A20, E20;A20, and E6b;A20) as well as a KIF5B-ALK fusion protein.
Thus, our test is an easily implementable diagnostic tool for the rapid, efficacious and cost-effective screening of ALK status in patients with lung cancer.
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors have dramatically changed the strategy of medical treatment of lung cancer.
In fact, the ALK (D5F3) CDx immunohistochemistry assay was approved by the US Food and Drug Administration as a standalone test for <i>ALK</i> rearrangements in lung cancer in 2015.
A definitive study randomizing patients with ALK-mutant lung cancer to crizotinib (also known as PF-02341066 or 1066) versus standard therapy has recently completed enrollment.Taken together, these data describe a trajectory of research progress from basic discovery science to real-world implementation that should serve as a model for future integration of preclinical and clinical therapeutic research.
Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370).
Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively.
The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients.
In this review, we will discuss the discovery of ALK rearrangements, the clinical epidemiology of lung cancer driven by ALK, the clinical data for ALK-targeted therapy in NSCLC, and ongoing ALK inhibitor-based clinical trials.