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|Ref Type||Journal Article|
|Authors||Wang W, Zhou J, Zhao L, Chen S|
|Title||Combination of SL327 and Sunitinib Malate leads to an additive anti-cancer effect in doxorubicin resistant thyroid carcinoma cells.|
|Journal||Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie|
|Abstract Text||Receptor tyrosine kinases (RTKs) play crucial roles in numerous cancer cell processes including cell survival, proliferation, and migration. MEK1/2 MAPK kinases are very important for cancer survival and development. Anaplastic thyroid carcinoma (ATC) is a deadly type of thyroid cancer and there are no very effective systemic treatment strategies for ATC so far. Also, ATC can easily become resistant to therapy of traditional therapeutic drugs for ATC, such as doxorubicin. Drug combination treatment could be a promising therapeutic strategy for ATC, especially for drug resistant ATC.We explored the combination effect between a MEK1/2 inhibitor SL327 and a multi-targeted RTK inhibitor Sunitinib Malate in doxorubicin resistant ATC cells using cell viability assay, cell migration assay, nuclei morphology and caspase-3 activity analysis, as well as in vivo tumor growth assay.There is a significant additive effect between SL327 and Sunitinib Malate in reducing viability, increasing apoptosis, and suppressing migration of doxorubicin-resistant ATC cells. Importantly, combination of SL327 and Sunitinib Malate induced significant additive suppression of in vivo doxorubicin-resistant ATC tumor growth.Our results suggest that the combination of MEK1/2 inhibitor and RTK inhibitor is promising for treatment of ATC especially doxorubicin-resistant ATC. The combination might not only enhance the anti-cancer efficacy, but also reduce the side effects and overcome drug resistance developed in ATC treatment. All these might provide useful information for clinical therapeutics of ATC.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|SL327||SL-327||MEK inhibitor (Pan) 22 MEK1 Inhibitor 20 MEK2 Inhibitor 18||SL327 inhibits MEK1 and MEK2, potentially resulting in decreased viability and increased apoptosis of tumor cells (PMID: 10969080, PMID: 28178630).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||thyroid gland cancer||not applicable||SL327 + Sunitinib||Preclinical - Cell line xenograft||Actionable||In a preclinical study, the combination of SL327 and Sutent (sunitinib) worked additively to decrease viability, induce apoptosis, and decrease migration of Taxotere (docetaxel)-resistant anaplastic thyroid cancer cell lines in culture, and to inhibit tumor growth in xenograft models (PMID: 28178630)||28178630|