Experimental Oncology Group

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Research Scientists

  • Sara García
  • Carmen Guerra

Post-Doctoral Fellows

  • Carolina Villarroya

Graduate Students

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

Technicians

  • Rebeca Barrero
  • Mª Carmen González
  • Silvia Jiménez
  • Teresa Laguna Lobo
  • Alejandra López
  • Marta San Román
  • Kika Annelotte Van Eck
  • Raquel Villar

The main area of interest of our Group is to identify therapeutic strategies against KRAS mutant lung and pancreatic tumours. For almost 4 decades, KRAS oncoproteins were thought to be undruggable targets. However, selective KRAS inhibitors, at least against one of the KRAS oncogenic isoforms, KRASG12C, have been recently approved by the FDA. Yet patients develop drug resistance rather quickly indicating that successful treatment of KRAS mutant tumours will require combination with inhibitors of KRAS signalling pathways, such as the MAP kinase and the PI3 kinase pathways. Unfortunately, all inhibitors tested thus far in the clinic have failed due to excessive toxicities. A potential exception is RAF1. Ablation of this kinase induced significant levels of tumour regression with limited toxicities in experimental models. Ironically, the tumour-inducing effect of RAF1 is not mediated by its kinase activity. Hence, pharmacological targeting of RAF1 will require the use of strategies capable of degrading the protein. To identify such compounds, we have determined the tertiary structure of the full RAF1 protein using Cryo-Electron Microscopy (Cryo-EM) technologies. These results have identified structural vulnerabilities that will make it possible to design selective RAF1 degraders.

Publications

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