Role of P2XRs in cancer and tissue regeneration

Main aim:

To address the homeostatic/regenerative versus the cancer-promoting role of P2XRs. Special focus will be placed on the role of P2XRs in tumor/host interaction and metastatic spreading and the pathophysiological meaning of the high extracellular eATP levels typical of the tumor microenvironment. 

Main Objectives:

1) Reach a consensus

1.a) on the role of P2XRs in cancer and tissue regeneration based on the critical analysis of the literature and the results from the Action members’ laboratories, and

1.b) on the efficacy of P2XR agonists versus antagonists to promote tumor regression or support regeneration of healthy tissues.

2) Identify human tumors amenable to be tackled by P2XR-targeting with academic laboratories and industrial partners’ joint effort.

3) Train Young Researchers and Innovators to investigate purinergic signaling in tumor models. 

Task 3.1: Collect and analyze current reports in the literature and from PRESTO’s members own laboratories on the role of P2XRs and eATP in cell proliferation, neovascularisation, and tumor-host interaction. Organize two meetings focused on the role of P2XRs in cancer and tissue regeneration. 

Task 3.2: Write consensus protocols to guide PRESTO members and other investigators in identifying the most appropriate animal models and pharmacological compounds to investigate P2XRs’ role in cancer and tissue regeneration. These consensus protocols will be published in major journals in the field (consensus papers). 

Task 3.3: Establish collaboration for joint experimental projects to test the efficacy of novel anti-cancer P2X7R-targeting drugs developed by the Action members and/or the members from Industries. 

Task 3.4: Define a roadmap for accelerated transfer of the most promising P2XR-targeting anti-cancer compounds from the preclinical to the clinical phase. This Task will be implemented with a close collaboration between preclinical investigators, clinicians, and members from industry. The Action will accomplish this aim by Short-Term Scientific Missions and specific meetings among PRESTO members belonging to different backgrounds. 

Task 3.5: Organize a training school on in vivo and ex vivo experimental cancer models. Attendants will learn advanced techniques for single-cell imaging, immune-tumor cells co-cultures, spheroids, tumoroids, Crispr/CAS9 gene-editing and metastasis mimicking assays.