Palliative treatment of pancreatic cancer

Abstract

Pancreatic cancer is one of the most serious problems of modern oncology. In the Russian Federation, pancreatic cancer, along with a fairly small share in the structure of the incidence of malignant neoplasms 3%, ranks first in annual mortality (68.2%), and is also a nosology with the most unfavorable prognosis among tumors of the gastrointestinal tract. The current standard of first-line therapy is FOLFRINOX (FOLFIRINOX, a combination of 5-fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin) or gemcitabine plus albumin-bound nab-paclitaxel. One of the main obstacles to the action of chemotherapeutic drugs is the microenvironment of fibro-solid stromal tumors, which include pancreatic cancer. In order to potentiate the action of chemotherapy and combat the tumor microenvironment, at the present stage, drugs are being considered for influencing the programmed death 1 (PD-1) gene and cytotoxic T-lymphocyte antigen 4 (CTLA-4). Approximately 1015% of malignant neoplasms of the pancreas are believed to be associated with hereditary mutations, while all neoplasms have somatic mutations in different combinations of driver genes. One of the most common mutations are BRCA1/BRCA2 gene mutations. Poly-ADP-ribose polymerase inhibitors, like cisplatin, have shown promise as a treatment for tumors with BRCA mutations. Another subtype of pancreatic cancer is characterized by microsatellite instability. Unlike the above mutations and phenotypes, which affect only a small proportion of patients with pancreatic cancer, mutations in KRAS (Kirsten homologous rat sarcoma viral oncogene) are found in 9095% of cases of pancreatic malignancy and may be a significant factor in pancreatic tumorigenesis. Another frequently mutating gene for a number of malignancies is ARID1A, which encodes a tumor suppressor protein, a subunit of the SWI/SNF chromatin remodeling complex. The future of conservative therapy for pancreatic cancer is a complex treatment that includes both chemotherapy and targeted therapy and immunotherapy, the implementation of which is impossible without a deeper study of genetic mutations, molecular mechanisms of invasion and development of pancreatic malignant neoplasms, as well as extensive testing for genetic mutations in the clinical practice of specialized institutions.