TORNA ALL’ELENCO

Therapeutic implications of translational research on malignant pleural mesothelioma in Respirology

2009
ASL Vercelli

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (1)

Mutti L

Abstract

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer refractory to treatment and poor prognosis whose incidence is progressively raising. Therefore new therapeutic approaches to treat it are definitively needed. Over the last years our knowledge on the mechanisms underlying the progressive transformation of human mesothelial (HMC) cells into MPM cells and on MPM progression and chemoresistance have been significantly clarified and these achievements allowed us to design new translational therapies for this neoplasm. Tyrosine Kinase Receptors (TKr) and their signalling transduction were shown to play a crucial role both in HMC transformation as well as in MPM progression and resistance to chemotherapy therefore the rationale on how TKr inhibitors could be used to treat MPM will be shown. NFkB activation was also shown to confer resistance to MPM providing a further rationale for new therapies. A significant role in asbestos dependent carcinogenesis depends on oxidative stress whereas MPM cells can repair DNA with great efficacy. These evidences suggested chemoprevention programs and another therapeutic approach aimed at hampering MPM well known chemoresistance. MPM intrinsic capability to act as Antigen Presenting Cells and elicit an immune response because of the expression of CTA and CTLA-4 antigens and surviving implied further translational approaches. Some derangements from normal apoptosis and gender-linked biological effects were also recently shown to offer new promising clinical implications too. Eventually a novel approach of treating MPM through miRNA inhibition will be discussedIn the light of these evidences the new chemopreventive and therapeutic trials are currently being tested or to be tested soon will be described. We are firmly convinced that within few years the better understanding of MPM genetic and molecular biology will be positively affecting the prognosis of patients with MPM.

DOI : 10.1111/j.1440-1843.2009.01656.x

Keywords

microRNA; tyrosine kinase receptor; antigen; DNA; asbestos; cytotoxic T lymphocyte antigen 4; pleura mesothelioma; therapy; prognosis; neoplasm; gender; molecular biology; patient; chemotherapy; oxidative stress; carcinogenesis; DNA repair; chemoprophylaxis; antigen presenting cell; immune response; mesothelium cell; human; achievement; apoptosis;