Supervisors info:
Θεοδόσιος Θεοδοσόπουλος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Πολυμενέας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Φραγκουλίδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Conventional therapeutic approaches to neoplastic disease, despite the tremendous advances made in recent years, show only moderate efficacy in the treatment of cancer, particularly advanced disease, while no therapeutic strategy ensures long disease-free survival or cure. The leaps and bounds in the field of molecular biology and genetics have revealed various mechanisms of pathogenesis of colorectal cancer (CRC). In particular, the discovery of new genes that correlated with carcinogenic pathways contributed to this. Today, the ultimate goal of all studies is to personalize treatment based on the individual's genetic profile. In recent years, the interest of scientists has focused on immunotherapy, a type of therapy aimed at enhancing and focusing the immune response against the neoplasm. Thinking about the direction of the immune response to cancer treatment is based on the close interaction of cancer and the immune system. Studies have revealed that any known immunological mechanism participates in the identification and elimination of residual cancer cells under physiological conditions. Tumors, however, are created when new cancer cells manage to escape from the immune system with various mechanisms. At this point, immunotherapy is applied, as it seeks to render cancer cells visible in a variety of ways, facilitating the immune system to destroy them by either blocking their proliferation or preventing the development of metastases. The immune system has great ability targeting tumor - destruction with almost zero toxicity to normal tissue, while maintaining long-term memory, thus preventing future disease recurrence. Developments in the field of cancer immunology in recent years have provided both knowledge and techniques to develop innovative immunotherapy regimens. As already mentioned, immunotherapy is the newest of a range of weapons in the fight against cancer. From this perspective of new treatment, colorectal cancer could not be excluded. The basic philosophy of this new drug is to enhance the patient's own immune system so that it can fight the "stranger" tissue. Tumors, as proven by a series of research protocols, have the ability to escape the immune system to survive and expand locally or to distant sites (metastases). The way to do this, is usually through the over-expression of molecules that act as brakes (the most popular are PD-L1, PD-1, CTLA4) in immune activation. Another way is to show a particular mild growth, to avoid any reaction from the defense mechanisms. In this way, by administering drugs that block the 'brakes', we release the function of immune mechanism against abnormal tumor cells. In colorectal cancer, the over-expression of the brake molecules is not so often observed, for this reason there was initially no research interest from the use of these molecules. Recently, however, new clinical trials showed that there is a subgroup of patients with advanced colorectal cancer, which appears to benefit from immunotherapy. These are patients whose tumors have microsatellite instability. The aim of the present study is to summarize the data on the role of PD-L1, both as a therapeutic agent and as a predictor, in patients with colorectal cancer. In addition, a brief presentation of clinical trials is under way. In conclusion, despite the significant steps taken recent years in immunotherapy and its administration to patients with malignancies, this therapeutic approach in patients with colorectal cancer remains under investigation, while the use of PD-L1 as a biomarker is questioned as the results of a multitude of studies are contradictory.
Keywords:
Colorectal cancer, Lynch syndrome, Molecular pathways of CRC, Molecular markers, Biomarkers, Prognostic and predictive markers in CRC, PD-1, PD-L1, Immunotherapy of CRC, Targeted therapy of CRC, Epidemiology of CRC
