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 1

5388 - GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype

Date

28 Sep 2019

Session

Poster Display session 1

Presenters

Pietro Paolo Vitiello

Citation

Annals of Oncology (2019) 30 (suppl_5): v1-v24. 10.1093/annonc/mdz238

Authors

P.P. Vitiello1, L. Mele2, C. Prisco2, C. Cardone1, D. Ciardiello1, L. Poliero1, C. Borrelli1, N. Zanaletti3, P. Vitale1, V. Tirino2, G. Papaccio2, T. Troiani1, F. Ciardiello1, F. Marampon4, V. Desiderio2, E. Martinelli1

Author affiliations

  • 1 Medicina Di Precisione, Università degli studi della Campania "Luigi Vanvitelli", 80131 - Naples/IT
  • 2 Medicina Sperimentale, Università degli studi della Campania "Luigi Vanvitelli", 80131 - Napoli/IT
  • 3 Medical Oncology, INCLIVA Biomedical Research Institute, 46010 - Valencia/ES
  • 4 Scienze Radiologiche, Oncologiche E Patologiche, Università di Roma "La Sapienza", 00161 - Roma/IT
More

Resources

Abstract 5388

Background

EPHA2 tyrosine kinase receptor is implicated in tumor progression, stemness phenotype and resistance to treatment in a wide range of cancers. We investigated the effects of GLPG1790, a new selective Eph receptor inhibitor, in colorectal cancer (CRC) across the 4 consensus molecular subtypes (CMS).

Methods

We tested the antiproliferative effect of GLPG 1790 used alone or in combination with either 5-fluorouracil, oxaliplatin or SN38 (the active metabolite of irinotecan) in a panel of 11 CRC cell lines encompassing the 4 consensus molecular subtypes (CMS). Cell cycle analysis was performed in order to understand possible cell cycle perturbation after treatment. Pathway analysis using western blot (WB) was also performed. We then evaluated the expression of stemness genes upon treatment using qRT-PCR.

Results

GLPG 1790 is active in CRC cell lines, with the strongest activity in the cell lines from the CMS4/mesenchymal-like cluster. Combination with chemotherapeutics is not synergistic according to Chou-Talalay model. The selective inhibitor elicits a persistent inactivation of EPHA2 receptor, associated to G0-G1 cell cycle block in the sensitive cell lines. Furthermore, GLPG 1790 is able to decrease the expression of cancer stem cell genes in cell lines belonging to the CMS4 group.

Conclusions

EPHA2 blockade using the selective inhibitor GLPG 1790 has a strong antiproliferative effect in the chemorefractory subgroup of CMS4/mesenchymal-like CRC cell lines, associated to a G0-G1 cell cycle arrest.

The stronger efficacy of GLPG1790 on the mesenchymal-like subtype is probably due to the impairment of cancer cell stemness and induction of cell differentiation after treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Università della Campania "Luigi Vanvitelli"; Galapagos NV (drug supply); Associazione Italiana per la Ricerca sul Cancro (AIRC).

Disclosure

P.P. Vitiello: Travel/Accommodation/Expenses: Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Ipsen; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Sanofi. C. Cardone: Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Roche. D. Ciardiello: Travel/Accommodation/Expenses: Sanofi. L. Poliero: Travel/Accommodation/Expenses: BMS. C. Borrelli: Travel/Accommodation/Expenses: BMS. N. Zanaletti: Travel/Accommodation/Expenses: BMS. P. Vitale: Travel/Accommodation/Expenses: BMS. T. Troiani: Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): Merck; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Servier; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Novartis. F. Ciardiello: Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Servier; Advisory/Consultancy: Pfizer; Research grant/Funding (institution): Ipsen. E. Martinelli: Honoraria (self), Research grant/Funding (institution): Amgen; Honoraria (self), Research grant/Funding (institution): Merck; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Honoraria (institution): Servier. All other 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