Your browser doesn't support javascript.
loading
EHMT1/2 inhibition promotes regression of therapy-resistant ovarian cancer tumors in a CD8 T cell-dependent manner.
Nguyen, Lily L; Watson, Zachary L; Ortega, Raquel; Woodruff, Elizabeth R; Jordan, Kimberly R; Iwanaga, Ritsuko; Yamamoto, Tomomi M; Bailey, Courtney A; To, Francis; Lin, Shujian; Villagomez, Fabian R; Jeong, Abigail D; Guntupalli, Saketh R; Behbakht, Kian; Gibaja, Veronica; Arnoult, Nausica; Chuong, Edward B; Bitler, Benjamin G.
Afiliación
  • Nguyen LL; University of Colorado Denver, Aurora, CO, United States.
  • Watson ZL; University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Ortega R; University of Colorado Boulder, Boulder, United States.
  • Woodruff ER; University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Jordan KR; University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Iwanaga R; University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
  • Yamamoto TM; University of Colorado Denver, Aurora, CO, United States.
  • Bailey CA; University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
  • To F; University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Lin S; University of Colorado Denver, Aurora, CO, United States.
  • Villagomez FR; University of Colorado Anschutz Medical Campus, Aurora, United States.
  • Jeong AD; University of Colorado Boulder, Boulder, CO, United States.
  • Guntupalli SR; University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Behbakht K; University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Gibaja V; Redona Therapeutics, Watertown, MA, United States.
  • Arnoult N; University of Colorado Boulder, United States.
  • Chuong EB; The University of Colorado Boulder, United States.
  • Bitler BG; University of Colorado Denver, Aurora, CO, United States.
Mol Cancer Res ; 2024 Aug 13.
Article en En | MEDLINE | ID: mdl-39136655
ABSTRACT
Poly ADP-ribose polymerase inhibitors (PARPi) are first-line maintenance therapy for ovarian cancer and an alternative therapy for several other cancer types. However, PARPi-resistance is rising and there is currently an unmet need to combat PARPi-resistant tumors. Here, we created an immunocompetent, PARPi-resistant mouse model to test the efficacy of combinatory PARPi and euchromatic histone methyltransferase 1/2 inhibitor (EHMTi) in the treatment of PARPi-resistant ovarian cancer. We discovered that inhibition of EHMT1/2 resensitizes cells to PARPi. Markedly, we show that single EHMTi and combinatory EHMTi/PARPi significantly reduced PARPi-resistant tumor burden and that this reduction is partially dependent on CD8 T cells. Altogether, our results show a low-toxicity drug that effectively treats PARPi-resistant ovarian cancer in an immune-dependent manner, supporting its entry into clinical development and potential incorporation of immunotherapy. Implications Targeting the epigenome of therapy-resistant ovarian cancer induces an anti-tumor response mediated in part through an anti-tumor immune response.
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Cancer Res Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Cancer Res Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos