ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance

ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance

The CDK inhibitor SNS-032 had previously exerted promising anti-neuroblastoma activity via CDK7 and 9 inhibition. ABCB1 expression was identified as major determinant of SNS-032 resistance. Here, we investigated the role of ABCB1 in acquired SNS-032 resistance. In contrast to ABCB1-expressing UKF-NB-3 sub-lines resistant to other ABCB1 substrates, SNS-032-adapted UKF-NB-3 (UKF-NB-3rSNS- 032300n...

Increased DNA Repair as a Mechanism of Acquired Resistance

A human ovarian cancer cell line, A2780, derived from an untreated ovarian cancer patient and relatively sensitive to cisplatin was treated by stepwise incubation with cisplatin to produce a cisplatin-resistant variant, 27X0"'. The relative abilities of these cell lines to repair cisplatin-induced damage to cellular DNA then was examined by measure of |3H|thymidine incorporation into normal den...

IGF1R depletion facilitates MET-amplification as mechanism of acquired resistance to erlotinib in HCC827 NSCLC cells

EGFR-mutated non-small cell lung cancer patients experience relapse within 1-2 years of treatment with EGFR-inhibitors, such as erlotinib. Multiple resistance mechanisms have been identified including secondary EGFR-mutations, MET-amplification, and epithelial-mesenchymal transition (EMT). Previous studies have indicated a role of Insulin-like growth factor 1 receptor (IGF1R) in acquired resist...

Mechanism of Action of SNS-032, a Novel Cyclin Dependent Kinase Inhibitor, in Chronic Lymphocytic Leukemia Short title: Transcriptional Inhibition by SNS-032 in CLL

Defective transport as a mechanism of acquired resistance to methotrexate in patients with acute lymphocytic leukemia.

Although the mechanisms of resistance to methotrexate (MTX) are known in experimental tumors made resistant to this drug, little information is available regarding acquired resistance to MTX in patients. A competitive displacement assay using the fluorescent lysine analogue of MTX, N-(4-amino-4-deoxy-N10-methylpteroyl)-N epsilon-(4'-fluorescein-thiocarbamyl)-L-lysine (PT430), was developed as a...