Proteïnes que de forma natural maten selectivament cèl·lules tumorals

Abstract

Tumour cells are characterized by deregulated apoptotic signalling, which causes uncontrolled proliferation and allows malignant cells to survive and be resistant to therapy. Conventional therapies such as chemotherapy, activate the induction of apoptosis, but there are tumour cells that evade this mechanism of death and, therefore, are resistant to treatment. In last years, the use of proteins that selectively kill cancer cells without causing toxic side effects to healthy tissues are being developed, thus increasing the hope of being able to improve in a near future new therapies against different types of cancer mainly those that are resistant to conventional therapies. These proteins interact with cell signalling pathways, redirecting the altered processes of survival and causing the death of transformed cells by mechanisms such as apoptosis, autophagy or mitotic catastrophe. The proteins that specifically kill tumour cells leaving unharmed the normal cells, can have two different origins, viral or cellular. There are viruses that code for proteins that can kill infected tumour cells by multiple mechanisms, taking the advantages that these cells are more vulnerable to virus infection and explaining their selective process. Among the viral proteins we find the chicken anemia virus-derived protein apoptin, adenovirus-derived protein E4orf4 and the parvovirus H1 NS1 protein. Regarding cellular proteins, it has been identified that the melanoma differentiation-associated gene-7 (MDA-7), the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and the human α-lactalbumin made lethal to tumour cells (HAMLET) present in human milk, also present therapeutic potential against cancer. The studies that at present are being carried out are aimed at knowing the specific signals of cell death that induce each one of these proteins as well as their mechanisms of action, which at present are not well known. Some of them, such MDA-7, TRAIL and HAMLET, are currently in phases I and II of clinical trials and show promising results