19P - Comparative effectiveness analysis of HSP90 inhibitors in non-small cell lung cancer

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anticancer agents
Thoracic Malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Angela Marrugal
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors A. Marrugal1, L. Ojeda Márquez1, Á. Quintanal2, S. Molina-Pinelo3, I. Ferrer1, A. Carnero4, L. Paz-Ares3
  • 1Oncología Molecular Y Nuevas Terapias, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 2Molecular Oncology And Novel Therapies, University Hospital 12 De Octubre, Madrid/ES
  • 3Molecular Oncology And Novel Therapies, University Hospital 12 De Octubre, 28041 Madrid - Madrid/ES
  • 4Cancer Molecular Biology, Hospital Universitario Virgen del Rocio, 41003 Sevilla - Sevilla/ES



Heat Shock Protein-90 (HSP90) over-expression has been related to poor prognosis in cancer. The role of this chaperone in malignancy is mediated by its ability to control the stabilization of known oncogenic client proteins. Therefore, the inhibition of HSP90 is a promising treatment strategy. One of the best response rates for HSP90 inhibition has been reported in non-small cell lung cancer (NSCLC). Nevertheless, the characterization of its efficacy in some molecularly defined subgroups will be key for successful clinical development.


Different human NSCLC cell lines carrying gene mutations whose relationship with HSP90 has been reported were used. Pharmacological inhibition of HSP90 activity in these cell lines were achieved through geldanamycin and resorcinol derivatives. The response to these inhibitors at different time points was evaluated.


Westerns blots indicated that HSP70 and HSP90-α protein expression were increased after 17-AAG, IPI-504, STA-9090 and AUY-922 treatments. EGFR, EML4-ALK and CDK4, the oncogenic client proteins studied, were depleted by the HSP90 inhibitors in the NSCLC cell lines. The strong relationship between client driver protein dependence on Hsp90 and the sensitivity to its inhibition was demonstrated in the HCC827 and H3122 cell lines.


The reduction of oncogenic client proteins alongside HSP70 and HSP90-α induction could be used as a validated biomarker signature of HSP90 inhibition in the cell lines studied. Future study will be focused on understanding the biological basis for the differential response to these treatments.

Clinical trial identification

Legal entity responsible for the study

Instituo de Biomedicina de Sevilla (IBIS) (CSIC, HUVR, Universidad de Sevilla)


Fundación para la Investigación de Sevilla (FISEVI)


All authors have declared no conflicts of interest.