Objective
The nervous system has recently been identified to play a central role in cancer pathogenesis, and this discovery has given birth to the burgeoning field of “cancer neuroscience”. Neurons and cancer cells outside the brain are known to communicate over paracrine signals, However, we recently discovered direct synaptic connections between sensory nerve endings and cancer cell membrane in a cancer outside the brain, i.e. pancreatic ductal adenocarcinoma (PDAC). These synaptic sites exhibit a selective enrichment of the glutamatergic NMDA receptor subunit GluN2D on the cancer cells, which enables PDAC cells to hijack the neurotransmitter L-glutamate over these cancer-neuron-synapses. This synaptic input not only aggravates tumor invasiveness and spread in vivo, but, surprisingly, also turns synaptically connected pancreatic cancer cells into electro-responsive, excitable cells via GluN2D-type glutamate receptors at the neuro-cancer synapses. Hence, we now have compelling evidence that pancreatic cancer cells are embedded into synaptically interconnected neuron-cancer networks in the pancreas. In the present study, we will perform the first real-time analysis of the emergence, evolution, function, and plasticity of synaptically interconnected neuron-cancer networks in PDAC. We will perform in vivo two-photon imaging focusing on these synapses in novel, human-like models of PDAC, will dissect their molecular operating mechanisms, and will assess the network activity over the neuron-cancer synapses directly in human PDAC specimens, but also in our novel “innervated organoids”. Finally, we will test the translational potential of the targeting this synaptic interconnection of pancreatic cancer cells with neurons in preclinical trials, coupled with in silico drug repurposing approaches. Therefore, through this comprehensive analysis of neuron-cancer synapses in PDAC, my vision is to open up new avenues for cancer neuroscience-instructed oncological therapies for PDAC.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences clinical medicine oncology prostate cancer
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
81675 Muenchen
Germany
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