Generation of Selective Citotoxicity in Tumor Cells by a Recombinant Bacterial Citolysin

MANZONE RODRIGUEZ, CLARISA; SAKA, HÉCTOR ALEX; BOCCO, JOSÉ LUIS; PAULA NANNINI

" Becas de Formación Inicial en Investigación en Cáncer" Informes Finales, Quinta Cohorte de Becarios [2016-2017]

Instituto Nacional del Cáncer

Año: 2018; p. 306 - 308

INTRODUCTION: Cancer is one of the main causes of mortality globally worldwide. Hallmarks of Cancer cells involve accumulation of mutations that give rise to features such as evasion of apoptosis, increased survival, angiogenesis, manipulation of the immune response, tissue invasion and metastasis. Although a broad spectrum of studies and therapies have been designed used, such as surgery, radiotherapy, immunotherapy, chemotherapy and hormones, their success is limited, relying mostly on the patient´s state at the beginning of the treatment, the tumor type and DNA mutations. The aim of this work is to develop a strategy based on gene therapy for cancer treatment, consistent on introduction of bacterial DNA in tumor cells. The gene selected for this study, hlyAP, encodes for the active form of the Vibrio cholerae pore-forming cytolysin (VCC), which is able to trigger different cell death pathways involving autophagy, apoptosis and necrosis, in a concentration-dependent manner. Thus, our aim is to take advantage of controlled induction of VCC expression in tumor cells to elicit cell death.