Grupo de Oncología Experimental

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Investigadores Científicos

  • Sara García
  • Carmen Guerra

Becarios Post-doctorales

  • Carolina Villarroya

Becarios Pre-Doctorales

  • Gonzalo María Aizpurua
  • Oksana Brehey
  • Laura De la Puente
  • Sara Barrambana
  • Ana María Fernández
  • Ana Galván
  • Lucía Lomba
  • Pian Sun
  • Elena Zamorano

Técnicos de Laboratorio

  • Rebeca Barrero
  • Mª Carmen González
  • Silvia Jiménez
  • Teresa Laguna Lobo
  • Vasiliki Liaki
  • Alejandra López
  • Marta San Román
  • Raquel Villar

The main thrust of our laboratory is to identify therapeutic strategies against KRAS mutant lung and pancreatic tumours. In recent years, inhibitors against KRAS oncoproteins selective for some of their mutations such as G12C and G12D, as well as panKRASG12X inhibitors active against all mutations, have been either approved by the FDA (sotorasib and adagrasib) or are undergoing clinical trials. Yet, their clinical efficacy is far from what was expected. In lung cancer patients, sotorasib does not increase overall survival compared to standard chemotherapy regimens due to the rapid appearance of tumour resistance. We have used genetically engineered mouse models of lung and pancreatic tumours to compare the therapeutic efficacy of KRAS ablation with that of KRAS inhibition, and to interrogate the molecular mechanism responsible for tumour resistance. Whereas ablation of KRAS oncogenes eliminates both lung and pancreatic tumours completely with no signs of tumour resistance, KRAS inhibition results in the rapid appearance of resistance as previously observed in human tumours. We are currently exploring whether inhibiting KRAS signalling at independent nodes within its downstream or upstream signalling pathways, as well as in orthogonal pathways, will not only increase tumour responses but also prevent the appearance of tumour resistance.

Publicaciones

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