Article ; Online: Targeted chemotherapy overcomes drug resistance in melanoma.
2020 Volume 34, Issue 9-10, Page(s) 637–649
Abstract: The emergence of drug resistance is a major obstacle for the success of targeted therapy in melanoma. Additionally, conventional chemotherapy has not been effective as drug-resistant cells escape lethal DNA damage effects by inducing growth arrest ... ...
| Abstract | The emergence of drug resistance is a major obstacle for the success of targeted therapy in melanoma. Additionally, conventional chemotherapy has not been effective as drug-resistant cells escape lethal DNA damage effects by inducing growth arrest commonly referred to as cellular dormancy. We present a therapeutic strategy termed "targeted chemotherapy" by depleting protein phosphatase 2A (PP2A) or its inhibition using a small molecule inhibitor (1,10-phenanthroline-5,6-dione [phendione]) in drug-resistant melanoma. Targeted chemotherapy induces the DNA damage response without causing DNA breaks or allowing cellular dormancy. Phendione treatment reduces tumor growth of BRAF |
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| MeSH term(s) | Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects ; DNA Damage/drug effects ; Drug Resistance, Neoplasm/drug effects ; Humans ; Melanoma/drug therapy ; Melanoma/enzymology ; Melanoma/physiopathology ; Protein Phosphatase 2/antagonists & inhibitors ; Pyrazoles/pharmacology | ||||||||||
| Chemical Substances | Antineoplastic Agents ; Pyrazoles ; Protein Phosphatase 2 (EC 3.1.3.16) ; phenidone (H0U5612P6K) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2020-04-02 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 806684-x | ||||||||||
| ISSN | 1549-5477 ; 0890-9369 | ||||||||||
| ISSN (online) | 1549-5477 | ||||||||||
| ISSN | 0890-9369 | ||||||||||
| DOI | 10.1101/gad.333864.119 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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