> Detailanzeige

Böhm, Michael J.; Marienfeld, Ralf; Jäger, Daniela; Mellert, Kevin; von Witzleben, Adrian; Brüderlein, Silke; Wittau, Mathias; von Baer, Alexandra; Schultheiss, Markus; Mayer-Steinacker, Regine; Rücker, Frank G.; Möller, Peter; Bullinger, Lars; Barth, Thomas F. E.

Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib
  • Beteiligte: Böhm, Michael J.; Marienfeld, Ralf; Jäger, Daniela; Mellert, Kevin; von Witzleben, Adrian; Brüderlein, Silke; Wittau, Mathias; von Baer, Alexandra; Schultheiss, Markus; Mayer-Steinacker, Regine; Rücker, Frank G.; Möller, Peter; Bullinger, Lars; Barth, Thomas F. E.
  • Erschienen: Hindawi Limited, 2019
  • Erschienen in: Sarcoma
  • Sprache: Englisch
  • DOI: 10.1155/2019/3914232
  • ISSN: 1357-714X; 1369-1643
  • Schlagwörter: Radiology, Nuclear Medicine and imaging ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.8%). It has been previously shown that the LMS cell line SK-LMS-1 has a defect in the p16 pathway and that this cell line can be inhibited by the CDK4 and CDK6 inhibitor palbociclib. For SK-LMS-1 we confirm and for SK-UT-1 we show that both LMS cell lines express CDK4 and that, in addition, strong CDK6 expression is seen in SK-LMS-1, whereas Rb was expressed in SK-LMS-1 but not in SK-UT-1. We confirm that inhibition of SK-LMS-1 with palbociclib led to a strong decrease in protein levels of Phospho-Rb (Ser780), a decreased cell proliferation, and G<jats:sub>0</jats:sub>/G<jats:sub>1</jats:sub>-phase arrest with decreased S/G<jats:sub>2</jats:sub>fractions. SK-UT-1 did not respond to palbociclib inhibition. To compare these<jats:italic>in vitro</jats:italic>findings with patient tissue samples, a p16, CDK4, CDK6, and p-Rb immunohistochemical staining assay of a large LMS cohort (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>99</mml:mn></mml:mrow></mml:math>patients with 159 samples) was performed assigning a potential responder phenotype to each patient, which we identified in 29 out of 99 (29.3%) patients. Taken together, these data show that CDK4/6 inhibitors may offer a new option for targeted therapy in a subset of LMS patients.</jats:p>
  • Zugangsstatus: Freier Zugang