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ONCOgenic Receptor Network of Excellence and Training 2.0

Periodic Reporting for period 1 - ONCORNET2.0 (ONCOgenic Receptor Network of Excellence and Training 2.0)

Reporting period: 2020-02-01 to 2022-01-31

Cancer is a leading health concern. There is a need to fully understand the fundamental processes underlying development of cancer. There is increasing evidence that G protein-coupled receptors (GPCRs) and their associated signalling cascades are involved in both cancer progression and metastasis. As oncogenic GPCRs are likely to be amenable to manipulation via drugs they are ideal 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, formerly known as CXCR7. Both receptors are highly expressed in a range of tumours and yet their role in cancer progression is not well understood. Within ONCORNET2.0 we will develop new strategies for CXCR4/ACKR3modulation (photochemistry, nanobodies) and investigate their effects on oncogenic responses, to yield key new knowledge and potential leads for drug development and commercialisation.

The key objective of this MSCA-ITN-ONCORNET2.0 initiative is to train the next generation of 15 ESRs by offering an extensive multidisciplinary training programme to ensure that they can operate in today’s drug discovery programmes. This includes both research (e.g. drug discovery, proteomics, imaging, modelling) and transferable (e.g. entrepreneurship, writing, media training) skill sets – that is rarely offered at PhD level.
15 ESRs were selected after an extensive recruitment conducted through the ONCORNET2.0 website and 1-day interview day at the Vrije Universiteit in Amsterdam. All have started their training between March and December 2020. During the Kick-off meeting and Workshop 1 in November 2020 they all met online and learned about the project set-up and goals. ONCORNET2.0 aims to extend and further strengthen the research lines set-up in the previous project ONCORNET on Modulators (WP3), Oncosignalling (WP4) and Translation (WP5). Additionally, an ESR focusing on Dissemination (WP6) has started. Within the WP3 new molecules (small molecules, nanobodies) have been generated and testing and use of these molecules in different experimental assays is ongoing. Within WP4 development of receptor systems (tagging WT/mutant receptors) and assays to unravel oncogenic signaling have been initiated. WP5 is focusing on the translational aspects and has been extended with the addition of partner from Luxembourg Institute for Health, with a 16th ESR looking into the role of opioids in ACKR3 function.
As of February 2021, biweekly online meetings with ESR presentations and Technology forums alternate; this way we aim to facilitate and strengthen the interactions amongst the ESRs and different research groups within Academia and SMEs.
Modulators developed in this consortium will be tested in the newly established in vitro signalling assays and potentially in the in vivo model systems. This will provide additional insight into a role of CXCR4 and/or ACKR3 in cancer. Impact of this network is expected in the last year of the network. Importantly, developed approaches within the ONCORNET2.0 programme are, like findings from ONCORNET, can be extrapolated to other (oncogenic) GPCRs. With the training and courses to come, students are able to personalise their career development plans based on their interests. Secondments planned will teach them if their interest is working with smaller or larger companies, start their own business and/or remain in research and development. Importantly, we are training ESRs to develop the next generation of multidisciplinary scientists with skills that are highly demanded by many of today’s employers in drug development industries.
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