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Epigenetic drugs and their molecular targets in testicular germ cell tumours.
Jostes, Sina; Nettersheim, Daniel; Schorle, Hubert.
Afiliación
  • Jostes S; Institute of Pathology, Department of Developmental Pathology, University of Bonn Medical School, Bonn, Germany.
  • Nettersheim D; Department of Urology, Urological Research Lab, Translational Urooncology, University Medical School Düsseldorf, Düsseldorf, Germany.
  • Schorle H; Institute of Pathology, Department of Developmental Pathology, University of Bonn Medical School, Bonn, Germany. Hubert.Schorle@ukbonn.de.
Nat Rev Urol ; 16(4): 245-259, 2019 04.
Article en En | MEDLINE | ID: mdl-30765888
Current treatment regimens for type II testicular germ cell tumours (TGCTs) achieve cure rates of ≥95%; however, 1-5% of TGCTs develop resistance to standard platinum-based chemotherapy. Patients with recurrent TGCT typically receive high-dose chemotherapy, but this treatment results in severe adverse effects and cytotoxicity. Thus, alternative treatment options should be considered to improve patient well-being and quality of life. Epigenetic drugs could be feasible options for TGCT treatment. Several compounds have already been tested in TGCT cell lines and xenograft models with promising results. These compounds include DNA demethylating agents (such as SGI-110), histone demethylase inhibitors (such as the lysine-specific histone demethylase 1A (LSD1) inhibitor CBB3001), histone deacetylase (HDAC) inhibitors (such as romidepsin) and bromodomain inhibitors (such as JQ1). Despite the diversity in their molecular effects, most epigenetic compounds show strong overlap in their genetic response. The use of epigenetic drugs in TGCTs triggers a cellular stress response, induction of differentiation and downregulation of genes associated with pluripotency, leading to growth arrest and apoptosis. Additive effects are seen using a combination of JQ1 and romidepsin. The availability of dual drugs (such as LSD1-HDAC1 hybrid inhibitors) could additionally take advantage of drug synergy effects. Thus, epigenetic drugs are novel tools that could be combined with standard therapy approaches to improve treatment of TGCTs.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Testiculares / Neoplasias de Células Germinales y Embrionarias / Epigénesis Genética / Antineoplásicos Aspecto: Patient_preference Límite: Humans / Male Idioma: En Revista: Nat Rev Urol Asunto de la revista: UROLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Testiculares / Neoplasias de Células Germinales y Embrionarias / Epigénesis Genética / Antineoplásicos Aspecto: Patient_preference Límite: Humans / Male Idioma: En Revista: Nat Rev Urol Asunto de la revista: UROLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido