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Multiomics analysis of serial PARP inhibitor treated metastatic TNBC inform on rational combination therapies.
Labrie, Marilyne; Li, Allen; Creason, Allison; Betts, Courtney; Keck, Jamie; Johnson, Brett; Sivagnanam, Shamilene; Boniface, Christopher; Ma, Hongli; Blucher, Aurora; Chang, Young Hwan; Chin, Koei; Vuky, Jacqueline; Guimaraes, Alexander R; Downey, Molly; Lim, Jeong Youn; Gao, Lina; Siex, Kiara; Parmar, Swapnil; Kolodzie, Annette; Spellman, Paul T; Goecks, Jeremy; Coussens, Lisa M; Corless, Christopher L; Bergan, Raymond; Gray, Joe W; Mills, Gordon B; Mitri, Zahi I.
Afiliación
  • Labrie M; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. labriem@ohsu.edu.
  • Li A; Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, USA. labriem@ohsu.edu.
  • Creason A; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Betts C; Computational Biology Program, Oregon Health and Science University, Portland, OR, USA.
  • Keck J; Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, USA.
  • Johnson B; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Sivagnanam S; Center for Spatial Systems Biomedicine (OCSSB), Oregon Health and Science University, Portland, OR, USA.
  • Boniface C; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Ma H; Center for Spatial Systems Biomedicine (OCSSB), Oregon Health and Science University, Portland, OR, USA.
  • Blucher A; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA.
  • Chang YH; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Chin K; Computational Biology Program, Oregon Health and Science University, Portland, OR, USA.
  • Vuky J; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
  • Guimaraes AR; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Downey M; Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, USA.
  • Lim JY; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Gao L; Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, USA.
  • Siex K; Computational Biology Program, Oregon Health and Science University, Portland, OR, USA.
  • Parmar S; Center for Spatial Systems Biomedicine (OCSSB), Oregon Health and Science University, Portland, OR, USA.
  • Kolodzie A; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA.
  • Spellman PT; Center for Spatial Systems Biomedicine (OCSSB), Oregon Health and Science University, Portland, OR, USA.
  • Goecks J; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA.
  • Coussens LM; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Corless CL; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Bergan R; Department of Diagnostic Radiology, Oregon Health and Science University, Portland, OR, USA.
  • Gray JW; Department of Diagnostic Radiology, Oregon Health and Science University, Portland, OR, USA.
  • Mills GB; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Mitri ZI; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
NPJ Precis Oncol ; 5(1): 92, 2021 Oct 19.
Article en En | MEDLINE | ID: mdl-34667258
ABSTRACT
In a pilot study, we evaluated the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities as they emerge under therapeutic stress engendered by poly-ADP-ribose polymerase (PARP) inhibitors (PARPi). In a BRCA-mutant basal breast cancer exceptional long-term survivor, a striking tumor destruction was accompanied by a marked infiltration of immune cells containing CD8 effector cells, consistent with pre-clinical evidence for association between STING mediated immune activation and benefit from PARPi and immunotherapy. Tumor cells in the exceptional responder underwent extensive protein network rewiring in response to PARP inhibition. In contrast, there were minimal changes in the ecosystem of a luminal androgen receptor rapid progressor, likely due to indifference to the effects of PARP inhibition. Together, identification of PARPi-induced emergent changes could be used to select patient specific combination therapies, based on tumor and immune state changes.
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: NPJ Precis Oncol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: NPJ Precis Oncol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos