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Predicting response to platinum and non-platinum drugs through bioluminescence resonance energy transfer (BRET) based bio-molecular interactions in platinum resistant epithelial ovarian cancer.
Bishnu, Aniketh; Mehrotra, Megha; Dhadve, Ajit; Dimri, Shalini; De, Abhijit; Ray, Pritha.
Afiliación
  • Bishnu A; Imaging Cell Signalling & Therapeutics Lab, Advanced Centre for Treatment, Research and Education in Cancer, TMC, Navi Mumbai 410210, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India.
  • Mehrotra M; Imaging Cell Signalling & Therapeutics Lab, Advanced Centre for Treatment, Research and Education in Cancer, TMC, Navi Mumbai 410210, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India.
  • Dhadve A; Imaging Cell Signalling & Therapeutics Lab, Advanced Centre for Treatment, Research and Education in Cancer, TMC, Navi Mumbai 410210, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India.
  • Dimri S; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India; Molecular Functional Imaging Lab, Advanced Centre for Treatment, Research and Education in Cancer, TMC, Navi Mumbai 410210, India.
  • De A; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India; Molecular Functional Imaging Lab, Advanced Centre for Treatment, Research and Education in Cancer, TMC, Navi Mumbai 410210, India.
  • Ray P; Imaging Cell Signalling & Therapeutics Lab, Advanced Centre for Treatment, Research and Education in Cancer, TMC, Navi Mumbai 410210, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400094, India. Electronic address: pray@actrec.gov.in.
Transl Oncol ; 14(11): 101193, 2021 Nov.
Article en En | MEDLINE | ID: mdl-34365218
Therapy induced rewiring of signalling networks often lead to acquirement of platinum-resistance, thereby necessitating the use of non-platinum agents as second-line treatment particularly for epithelial ovarian cancer (EOC). A prior subject-specific assessment can guide the choice of optimal non-platinum agent/s and possible targeted therapeutic/s. Assessment of protein-protein interactions are superior to simple cytotoxicity assays to determine therapeutic efficacy and associated molecular responses. Utilizing improved PIP3-AKT and ERK1/2 activation Bioluminescence Resonance Energy Transfer (BRET) sensors, we report chemotherapy-induced ERK1/2 activation predominantly in cisplatin-paclitaxel resistant EOC cells and increased activation of both ERK1/2 and AKT in malignant ascites derived cancer cells from platinum-resistant patients but not from treatment-naive or platinum-sensitive relapse patients. Further, majority of the non-platinum drugs except irinotecan increased ERK1/2 activation in platinum-taxol resistant cells as observed by live-cell BRET assessment which were associated with p90RSK1/2 and BAD activation along with upregulation of multidrug transporter gene ABCC1 and cell survival genes like cyclin D1 and Bcl2. Interestingly, only irinotecan was able to sensitize these resistant cells. Altogether, this first report of BRET based sensing of molecular pathway activations in platinum resistant cell lines and patient's derived cancer cells highlight the clinical potential of BRET sensors in management of therapy resistant cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Transl Oncol Año: 2021 Tipo del documento: Article País de afiliación: India 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 Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Transl Oncol Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos