Papel da interação MUC16-mesotelina na disseminação peritoneal do carcinoma do ovário

Uma equipa de investigadores do Ipatimup/i3S publicou um artigo de revisão em colaboração com investigadores do centro Hospitalar de São João, na revista Expert Review of Anticancer Therapy, onde revêm o papel da expressão e interação entre a mucina 16 (MUC16) e a mesotelina na disseminação peritoneal do carcinoma de ovário. Este artigo fornece uma extensa revisão sobre os ensaios clínicos que têm como alvo terapêutico a expressão destas duas moléculas. Com base nas evidências científicas reportadas na literatura, os autores defendem que as terapias que tenham como alvo MUC16/mesotelina constituem uma relevante opção terapêutica para interferir com a disseminação peritoneal do carcinoma de ovário.

Autores e Afiliações:
Ricardo Coelho 1,2, Lara Marcos-Silva 1, 3, Sara. Ricardo 1,2, Filipa Ponte 1, Antónia Costa 2,4,5, José Manuel Lopes 2,6,7, Leonor David 1,2

(1) Differentiation and Cancer Group, IPATIMUP/i3S, Institute of Molecular Pathology and Immunology of the University of Porto/Institute for Research and Innovation in Health of University of Porto, Porto, Portugal.

(2) FMUP, Faculty of Medicine of University of Porto, Porto, Portugal.

(3) Animal Cell Technology Unit, ITQB, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Lisboa, Portugal and iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.

(4) Gynecology and Obstetrics Department, Centro Hospitalar S. João, Porto, Portugal.

(5) Monitoring and simulation of perinatal asphyxia group, INEB/i3S, Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal/ Institute for Research and Innovation in Health of University of Porto, Porto, Portugal

(6) Pathology Department, Centro Hospitalar S. João, Porto, Portugal.

(7) Cancer Cell Signalling and Metabolism Group, IPATIMUP/i3S, Institute of Molecular Pathology and Immunology of the University of Porto/Institute for Research and Innovation in Health of University of Porto, Porto, Portugal.

Abstract:
Peritoneal dissemination is a particular form of malignant progression in ovarian cancer, preceding hematogenic or lymphatic dissemination. Thus, prevention of peritoneal implantation of cancer cells is envisioned to inhibit neoplastic dissemination and therefore prolong disease remission and patient's survival. Areas covered: An extended review on the role of MUC16 (CA125) and mesothelin (MSLN), expressed in a high percentage of ovarian carcinomas, indicate that this duet is relevant for the contact between cancer cells and mesothelial cells in homotypic (cancer cell-cancer cell) and heterotypic (cancer cell-mesothelial cell) interactions. This review discusses the reasons underlying the clinical failure of immunotherapeutic strategies targeting MUC16. Clinical data on MSLN targeting agents such as antibody-based immunotoxins cialis pas cher or antibody drug conjugates are also reviewed. The promising anti-tumor effect of CAR-T cells directed to MUC16 or MSLN is emphasized. New emerging strategies specifically disrupting the MUC16-MSLN interaction are at the forefront of this review, including TRAIL ligands bound to MSLN targeting MUC16 expressing cells and single chain monoclonal antibodies and immunoadhesins recognizing MSLN-MUC16 binding domains. Expert commentary: Based on existing evidences the authors advocate that agents targeting MUC16-MSLN may add to the therapeutic armamentarium directed to abrogate peritoneal homing of ovarian cancer.

Revista: Expert Review of Anticancer Therapy

Link: http://www.tandfonline.com/doi/full/10.1080/14737140.2018.1418326