In this study, we assessed whether the presence of polymorphisms in ERCC1, XPD, RRM1 and MDR1 genes can affect the efficacy and the tolerability of cisplatin and vinorelbine in NSCLC patients.
Down-regulation of ADAMTS1 was observed in 30% (3/10) of the NSCLC cell lines, and this down-regulation was found to be concordant with aberrant methylation of the gene.
Chromosomal translocations and single point mutations involving the Anaplastic Lymphoma Kinase (ALK) gene have been described in several human tumors, including anaplastic large cell lymphoma (ALCL), non-small cell lung cancer (NCSLC), inflammatory myofibroblastic tumor (IMT) and neuroblastoma.
At the moment, established personalized treatment approaches include treatment of patients with NSCLC and activating epidermal growth factor receptor (EGFR) mutations with the EGFR-directed tyrosine kinase inhibitors gefitinib or erlotinib, and treatment of NSCLC patients with genetic aberrations in the anaplastic lymphoma kinase (ALK) oncogene with the mesenchymal-epithelial transition factor (MET)/ALK inhibitor crizotinib.
Current data on the efficacy and toxicity of crizotinib are also examined, and future directions for the treatment of NSCLC positive for ALK rearrangement are addressed.
We selected NSCLC cell lines--A549 (KRAS G12S), NCI-H3255 (EGFR L858R), NCI-H3122 (EML4-ALK E13;A20), and HCC78 (SLC34A2-ROS1)-to evaluate the antiproliferative effects of submicromolar concentrations of the multitargeted TKIs imatinib, sorafenib, erlotinib, and crizotinib.
Rapid and dramatic radiographic and clinical response to an ALK inhibitor (crizotinib, PF02341066) in an ALK translocation-positive patient with non-small cell lung cancer.
Ongoing studies will define the true utility of this drug in ALK-rearranged non-small-cell lung cancer patients and in patients with other tumors that also have ALK activation.
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization-positive nonsmall cell lung cancer.
While understanding molecular mechanisms of resistance is critical to overcome therapeutic resistance, understanding physiologic mechanisms of resistance through analyzing anatomic patterns of failure may be equally crucial to improve long-term survival for patients with EML4-ALK translocation positive NSCLC.
The EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene.
In an ALK-enriched population, patients with metastatic non-small cell lung cancer were screened by ALK fluorescence in situ hybridization and for epidermal growth factor receptor (EGFR) and KRAS mutations.
We examined overall survival in patients with advanced, ALK-positive NSCLC who enrolled in the phase 1 clinical trial of crizotinib, focusing on the cohort of 82 patients who had enrolled through Feb 10, 2010.
For comparison, we evaluated 266 patients with advanced, ALK-negative, epidermal growth factor receptor (EGFR)-wild-type NSCLC, including 79 with KRAS mutations and 187 with wild-type KRAS (WT/WT/WT).
Crizotinib, an inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), achieves response rates of 57 % at eight weeks in patients with stage IV non-small cell lung cancer with ALK rearrangements.