Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5485 - High-throughput screening of new drugs targeting lung CSCs

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Héctor Amado Labrador

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

H.A. Amado Labrador1, E. Jantus-Lewintre2, S. Calabuig Fariñas3, C. Aguilar-Gallardo4, J. Murga5, E. Munera-Maravilla6, E. Durendez-Saez4, M. Mosqueda6, E. Escorihuela4, F. ZHANG6, E. Masiá7, N. Dong8, R. Guijarro9, C. Camps10

Author affiliations

  • 1 Fundación Carolina/bbva, Molecular Oncology Laboratory, Fundación de Investigación Hospital General Universitario de Valencia., 46014 - Valencia/ES
  • 2 Molecular Oncology Laboratory, Fundación Para La Investigación Hospital General Universitario De Valencia-ciberonc., Biotechnology Department, Universitat Politécnica de València, 46014 - Valencia/ES
  • 3 Pathology Department, Universitat De València., Molecular Oncology Laboratory, Hospital General Universitario de Valencia - CIBERONC., 46018 - Valencia/ES
  • 4 Molecular Oncology Laboratory, Fundación de Investigación Hospital General Universitario de Valencia - CIBERONC, 46014 - Valencia/ES
  • 5 Departamento De Química Inorgánica Y Orgánica, Universidad Jaume I, 12071 - Castellón/ES
  • 6 Molecular Oncology Laboratory, Fundación de Investigación Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 7 Laboratorio De Polímeros Terapeúticos, Centro de Investigación Príncipe Felipe, 46012 - Valencia/ES
  • 8 Molecular Oncology Laboratory, Fundación de Investigación Hospital General Universitario de Valencia, 46014 - valencia/ES
  • 9 Medicine Department, Universitat De València, Thoracic Surgery Department, Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 10 Medicine Department, Universitat De València, Medical Oncology, Consorcio Hospital General Universitario de Valencia -CIBERONC, 46014 - Valencia/ES
More

Resources

Abstract 5485

Background

Non-small cell lung cancer (NSCLC), the most common subtype of lung cancer, is characterized by low response rates and a poor prognosis. The majority of patients are diagnosed in advanced stages, where chemotherapy remains the gold standard of treatment. However, the resistance has been associated to cancer stem cells (CSCs), a highly tumorigenic subpopulation of cells with the ability to grow as spheres in non-adherent conditions. The aim of this study was to discover novel therapeutic strategies through screening platforms in order to target CSCs population.

Methods

High-throughput screening with commercial chemical libraries (Prestwick and Myria) was performed, comparing cytotoxic effect in monolayer cells vs. lung-tumorspheres derived from 8 resected NSCLC patients and 11 NSCLC cell lines. Compounds were added per triplicates at different concentrations (0.01 to 50 µM). Cell viability was measured after 48h using MTS Assay. Consecutively, 8 tumors were induced by inoculating resected NSCLC patient and H1650 lung-tumor-spheroids in NOD/SCID mice. Selected drugs were administered intraperitoneally (3 times a week, 100 mg/kg). Characterization of the inhibition pathway involved in the mechanism of action of these drugs was performed by RT-qPCR.

Results

Three drugs of the commercial chemical libraries (DSF, Compound 1 and Compound 2) were identified with greater cytotoxic potential against lung tumorspheres, compared to a poor or null effect on monolayer cells. These results were validated in vivo, which demonstrated the capacity of these drugs to inhibit tumor growth in mice treated respect to the control (Table). We are currently characterizing the signaling pathways involved in the mechanism of action of these drugs.

Conclusions

Our findings reveal that these drugs can inhibit CSCs like properties, as evidenced in the lung tumorspheres in vitro and in vivo assays. Therefore, these compounds could be a promising targeted therapy as potential inhibitors of lung CSCs.Table: 1889P

Percentage of tumor reduction in the mice treated respect to the control

Mice (Line/Patient)Tumor Volume (mm3)Tumor Reduction (%)
H1650_CNT1593,11
H1650_DSF541,4466.02
H1650_Compound 1483,7269.64
H1650_Compound 2276,9882.62
Patient_CNT1645,68
Patient_DSF49070,23
Patient Compound 1721,5656,16
Patient Compound 2102038,02

Clinical trial identification

Legal entity responsible for the study

Fundación para la Investigación Hospital General Universitario de Valencia.

Funding

Supported by ISCIII (P12-02838 / FIS P15-00573).

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings