Targeted chemotherapy overcomes drug resistance in melanoma.


Journal

Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660

Informations de publication

Date de publication:
01 05 2020
Historique:
received: 18 10 2019
accepted: 13 03 2020
pubmed: 4 4 2020
medline: 31 10 2020
entrez: 4 4 2020
Statut: ppublish

Résumé

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

Identifiants

pubmed: 32241802
pii: gad.333864.119
doi: 10.1101/gad.333864.119
pmc: PMC7197350
doi:

Substances chimiques

Antineoplastic Agents 0
Pyrazoles 0
Protein Phosphatase 2 EC 3.1.3.16
phenidone H0U5612P6K

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

637-649

Subventions

Organisme : NCI NIH HHS
ID : DP1 CA228041
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA240139
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM078455
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM105754
Pays : United States

Informations de copyright

© 2020 Yue et al.; Published by Cold Spring Harbor Laboratory Press.

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Auteurs

Jingyin Yue (J)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Roberto Vendramin (R)

Laboratory for Molecular Cancer Biology, Oncology Department, KULeuven, 3000 Leuven, Belgium.
Center for Cancer Biology, VIB, 3000 Leuven, Belgium.

Fan Liu (F)

Department of Biochemistry, University of Miami, Miami, Florida 33136, USA.

Omar Lopez (O)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Monica G Valencia (MG)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Helena Gomes Dos Santos (H)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Gabriel Gaidosh (G)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Felipe Beckedorff (F)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Ezra Blumenthal (E)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Lucia Speroni (L)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Stephen D Nimer (SD)

Department of Biochemistry, University of Miami, Miami, Florida 33136, USA.
Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Jean-Christophe Marine (JC)

Laboratory for Molecular Cancer Biology, Oncology Department, KULeuven, 3000 Leuven, Belgium.
Center for Cancer Biology, VIB, 3000 Leuven, Belgium.

Ramin Shiekhattar (R)

Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

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Classifications MeSH