PRIN_DI MARZO_Unravelling the role of TRPM8 in colon carcinogenesis: a new chance for diagnosis, chemoprevention and treatment (DCM.AD007.103)

Area tematica

Scienze chimiche e tecnologie dei materiali

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di chimica biomolecolare (ICB)

Responsabile di progetto

VINCENZO DIMARZO
Telefono: 0818675330
E-mail: vincenzo.dimarzo@cnr.it

Abstract

Colorectal cancer (CRC) is a relevant cause of morbidity and mortality. TRPM8, a member of the TRP channels superfamily, is up-regulated in a number of tumours. However, its role in colon carcinogenesis
(CC) is largely unexplored.
We will examine the role of TRPM8 in CC by using an integrated multidisciplinary preclinical approach comprising mouse models of CC (colitis-associated cancer, APC mice and xenograft model), pharmacological experiments in CRC cells (including in 5-fluorouracil-resistant cells) and assays (TRPM8 expression) in colonic samples and blood from stage I-IV CRC patients. We will also evaluate: i) possible changes in gut microbiota associated to TRPM8 modulation ii) the possible chemopreventive effect of a diet containing safe naturally-occurring TRPM8 ligands.
Our proposal is supported not only by literature data, but also by our preliminary (unpublished) pharmacological results on a mouse model of CC and on TRPM8 expression in colonic samples from CRC
patients.

Obiettivi

Objective 1. Exploring possible adaptive changes of trpm8 in human samples as well as its potential prognostic role in colorectal cancer (CRC)
Objective 2. Unravelling the role of TRPM8 in CRC cells.
Objective 3. Evaluating the possible additive/synergistic effects of TRPM8 ligands in combination with currently-used antitumoural drugs
Objective 4. Unravelling the physiopathological and pharmacological role of TRPM8 in experimental models of colon carcinogenesis
Objective 5. Investigating the effect of experimental colon carcinogenesis on TRPM8 expression
Objective 6. Investigating the intracellula pathways related to TRPM8-induced effects in murine colonic segments
Objective 7. Investigating the gut microbiota in colitis-associated cancer (CAC)
Objective 8. Searching a safe nutraceutical strategy for CRC prevention
Objective 9. Synthesis of TRPM8 agonists and antagonists

Data inizio attività

29/08/2019

Parole chiave

TRPM8, colorectal cancer, gut microbiota

Ultimo aggiornamento: 30/04/2024