Cancer is a major health burden responsible for 20% of European deaths. There is a critical need to understand its fundamental biological mechanisms. G protein-coupled receptors (GPCRs) are cell surface proteins which play an important role in regulating cellular functions integral to cancer biology and, as highly druggable proteins, oncogenic GPCRs are important therapeutic targets. ONCORNET2.0 builds on the success of ONCORNET (Oncogenic GPCR Network of Excellence and Training), a first-in-kind ETN in GPCR drug discovery that has successfully delivered scientific advance and training to talented early stage researchers (ESRs). ONCORNET2.0 will incorporate recent scientific and technological advances to understand and target two oncogenic GPCRs; the chemokine receptors CXCR4 and ACKR3 (CXCR7). These are highly expressed in multiple tumours but their role in cancer progression remains poorly understood. We will develop new strategies for CXCR4/ACKR3 modulation (photochemistry, nanobodies) and investigate their effects on oncogenic responses, to yield key new knowledge and potential leads for drug development and commercialisation.
ONCORNET2.0 will bring together the leading GPCR research groups in Europe and 15 Early Stage Researchers (ESRs). By leveraging on the success and experience of ONCORNET and recent ground-breaking advances in the field of GPCRs (e.g. cryo-EM, CRISPR-Cas, advanced microscopy), ONCORNET2.0 brings a young, gender balanced team of PIs to target oncogenic GPCRs. The consortium will offer an extensive multidisciplinary training programme for ESRs ensuring their successful incorporation in today’s fast-moving drug development programmes. This programme integrates both research and transferable skill sets through blended learning. Our aim is that, through training these ESRs with interdisciplinary and intersectoral exposure, we will develop the next generation of scientists with skills that are in high demand by the drug development industries but rarely offered academically.
Figure – G protein-(in)dependent signalling and trafficking by GPCR mono/homo/heteromers in nanodomains
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VU University Amsterdam