Inhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-Induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules
MetadataShow full item record
Resistance to chemotherapy represents a major obstacle for long-term remission, and effective strategies toovercome drug resistance would have significant clinical impact. We report that recurrent ovarian carcinomas after paclitaxel/carboplatin treatment have higher levels of spleen tyrosine kinase (SYK) and phospho-SYK. Invitro, paclitaxel-resistant cells expressed higher SYK, and the ratio of phospho-SYK/SYK positively associated with paclitaxel resistance in ovarian cancer cells. Inactivation of SYK by inhibitors or gene knockdown sensitized paclitaxel cytotoxicity invitro and invivo. Analysis of the phosphotyrosine proteome in paclitaxel-resistant tumor cells revealed that SYK phosphorylates tubulins and microtubule-associated proteins. Inhibition of SYK enhanced microtubule stability in paclitaxel-resistant tumor cells that were otherwise insensitive. Thus, targeting SYK pathway is a promising strategy to enhance paclitaxel response.
Showing items related by title, author, creator and subject.
Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/ HER2-negative breast cancer-the evaluating treatment with neoadjuvant abraxane (ETNA) trial a randomized phase 3 clinical trialGianni, L.; Mansutti, M.; Anton, A.; Calvo, L.; Bisagni, G.; Bermejo, B.; Semiglazov, V.; Thill, M.; Chacon, J.; Chan, Arlene; Morales, S.; Alvarez, I.; Plazaola, A.; Zambetti, M.; Redfern, A.; Dittrich, C.; Dent, R.; Magazzu, D.; De Fato, R.; Valagussa, P.; Tusquets, I. (2018)© 2018 American Medical Association. All rights reserved. IMPORTANCE Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) ...
A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4)Martín, M.; Chan, Arlene; Dirix, L.; O'Shaughnessy, J.; Hegg, R.; Manikhas, A.; Shtivelband, M.; Krivorotko, P.; Batista López, N.; Campone, M.; Ruiz Borrego, M.; Khan, Q.; Beck, J.; Ramos Vázquez, M.; Urban, P.; Goteti, S.; Di Tomaso, E.; Massacesi, C.; Delaloge, S. (2017)© The Author 2016.Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. ...
Synergistic Anticancer Effects Achieved by Co-Delivery of TRAIL and Paclitaxel Using Cationic Polymeric MicellesLee, A.; Wang, Y.; Pervaiz, Shazib; Fan, W.; Yang, Y. (2011)Cationic micellar nanoparticles self-assembled from a biodegradable amphiphilic copolymer have been used to deliver human TRAIL and paclitaxel simultaneously. Polyplexes formed between paclitaxel-loaded nanoparticles and ...