Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy
Identifieur interne : 000620 ( Main/Exploration ); précédent : 000619; suivant : 000621Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy
Auteurs : Maria Mrakovcic [Allemagne] ; Leopold F. FröhlichSource :
- Cancers [ 2072-6694 ] ; 2019.
Abstract
Histone deacetylation inhibitors (HDACi) offer high potential for future cancer therapy as they can re-establish the expression of epigenetically silenced cell death programs. HDACi-induced autophagy offers the possibility to counteract the frequently present apoptosis-resistance as well as stress conditions of cancer cells. Opposed to the function of apoptosis and necrosis however, autophagy activated in cancer cells can engage in a tumor-suppressive or tumor-promoting manner depending on mostly unclarified factors. As a physiological adaption to apoptosis resistance in early phases of tumorigenesis, autophagy seems to resume a tumorsuppressive role that confines tumor necrosis and inflammation or even induces cell death in malignant cells. During later stages of tumor development, chemotherapeutic drug-induced autophagy seems to be reprogrammed by the cancer cell to prevent its elimination and support tumor progression. Consistently, HDACi-mediated activation of autophagy seems to exert a protective function that prevents the induction of apoptotic or necrotic cell death in cancer cells. Thus, resistance to HDACi-induced cell death is often encountered in various types of cancer as well. The current review highlights the different mechanisms of HDACi-elicited autophagy and corresponding possible molecular determinants of therapeutic resistance in cancer.
Url:
DOI: 10.3390/cancers12010109
PubMed: 31906235
PubMed Central: 7016854
Affiliations:
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Fröhlich</name><affiliation><nlm:aff id="af1-cancers-12-00109">Department of Cranio-Maxillofacial Surgery, University of Münster, 48149 Münster, Germany;<email>leopold.froehlich@ukmuenster.de</email></nlm:aff></affiliation></author></analytic><series><title level="j">Cancers</title><idno type="eISSN">2072-6694</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Histone deacetylation inhibitors (HDACi) offer high potential for future cancer therapy as they can re-establish the expression of epigenetically silenced cell death programs. HDACi-induced autophagy offers the possibility to counteract the frequently present apoptosis-resistance as well as stress conditions of cancer cells. Opposed to the function of apoptosis and necrosis however, autophagy activated in cancer cells can engage in a tumor-suppressive or tumor-promoting manner depending on mostly unclarified factors. As a physiological adaption to apoptosis resistance in early phases of tumorigenesis, autophagy seems to resume a tumorsuppressive role that confines tumor necrosis and inflammation or even induces cell death in malignant cells. During later stages of tumor development, chemotherapeutic drug-induced autophagy seems to be reprogrammed by the cancer cell to prevent its elimination and support tumor progression. Consistently, HDACi-mediated activation of autophagy seems to exert a protective function that prevents the induction of apoptotic or necrotic cell death in cancer cells. Thus, resistance to HDACi-induced cell death is often encountered in various types of cancer as well. 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Horwitz</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>District de Münster</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Münster</li></settlement></list><tree><noCountry><name sortKey="Frohlich, Leopold F" sort="Frohlich, Leopold F" uniqKey="Frohlich L" first="Leopold F." last="Fröhlich">Leopold F. Fröhlich</name></noCountry><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Mrakovcic, Maria" sort="Mrakovcic, Maria" uniqKey="Mrakovcic M" first="Maria" last="Mrakovcic">Maria Mrakovcic</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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