NCT02293811: P2RX7

Decoding of the Expression of Tumor Suppressor P2RX7 in Inflammatory and Malignant Colonic Mucosa

Terminated NA Last updated 18 March 2024

What this trial tests

NA trial testing Analysis in Crohn Disease-Associated Colorectal Adenocarcinoma in 50 participants. Terminated before completion.

Timeline

9 February 2015

Primary endpoint
15 October 2015

15 December 2015

Quick facts

Lead sponsor	Centre Hospitalier Universitaire de Nice
Phase	NA
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	50
Start date	9 February 2015
Primary completion	15 October 2015
Estimated completion	15 December 2015
Sites	1 location across France

Drugs / interventions tested

• Analysis

Conditions studied

• Crohn Disease-Associated Colorectal Adenocarcinoma — all drugs for Crohn Disease-Associated Colorectal Adenocarcinoma →

Sponsor

Centre Hospitalier Universitaire de Nice

Who can join

18 and older, any sex, with Crohn Disease-Associated Colorectal Adenocarcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The inflammatory tumor micro-environment is a consequence and a driver of tumorogenesis. On one hand it promotes antitumor immune responses and on the other hand it favors development and progression of cancerous lesions.

Factors regulating the complex interplay between epithelial and immune cells are still poorly characterized. Extracellular ATP (eATP) acting on the purinergic P2X7 receptors (P2RX7) has recently emerged as a key signaling pathway in the immune response.

Recent data have revealed the crucial role of P2RX7-NLRP3-Caspase-1 for priming dendritic cells (DC) within the tumor microenvironment upon treatment with certain types of chemotherapy drugs. Despite this important discovery, no previous study has so far investigated the global in vivo effect of P2RX7 modulation in inflammation-induced carcinogenesis of mucosal tissues.

Our consortium, endowed by a long standing experience in the field of mucosal immunology, inflammation and signaling, already demonstrated that the P2RX7 is differentially expressed in the mucosa of patients with active and quiescent inflammatory bowel disease (IBD), where eATP is present at very high concentration, and that P2RX7 controls an amplification loop of the inflammatory response (Cesaro et al., 2010). Furthermore, we uncovered that P2RX7 controls homeostasis, survival and function of regulatory T cells (Hubert et al., 2010). In addition, our recent demonstration that P2RX7 deficiency lowered mucosal inflammation but unexpectedly enhanced tumor formation in vivo warrants additional efforts to explore the molecular and cellular mechanisms accounting for this effect and suggest that enhancing P2RX7 function may have an anti-tumor therapeutic effect.

These observations emphasize the tumor suppressor role of P2X7 receptor, warrant further investigation to better understand the molecular mechanisms responsible for this anti-tumor effect and suggest that enhancing the function of P2X7R could have a therapeutic effect significant antitumor.

Our main objectives is to explore the role of P2RX7 in healthy, inflammatory and cancerous colonic mucosa. For this we will map the expression of the protein P2RX7 and realize genotype of P2RX7 forms in inflammatory diseases and cancer of the colon.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Purine and purinergic receptors in health and disease.
   Ai Y, Wang H, Liu L, Qi Y, et al · · 2023 · cited 25× · PMID 37692109 · DOI 10.1002/mco2.359
2. Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas.
   Hey G, Rao R, Carter A, Reddy A, et al · · 2023 · cited 9× · PMID 37241023 · DOI 10.3390/jpm13050853