Molecular markers of colorectal cancer, association with objective tumor response to treatment

Introduction. Colorectal cancer (CRC) is one of the leading causes of death from cancer in the world and is also one of the most common forms of oncological pathology, which is characterized by a continuing steady increase in morbidity, a significant incidence of relapses, and early metastasis. Among the many signaling cascades that determine the features of the biological behavior of a tumor, great importance is attached to the AKT / mTOR signaling pathway. The study aimed to study the expression of AKT / mTOR signaling pathway components in tumors in patients with colorectal cancer, in connection with the clinical and morphological parameters of the disease and the objective response of the tumor to antitumor treatment. Materials and methods. The study included 26 patients with colorectal cancer aged 43 to 75 years (average age was 54 years). In the clinics of the Research Institute of Oncology of the Tomsk National Research Medical Center, patients received combined treatment, which included neoadjuvant chemotherapy according to the FOLFOX or XELOX scheme by radical surgery. The study material was normal and tumor tissue was obtained after surgical treatment. The mRNA level of the studied parameters was determined by real-time PCR. Results and discussion. A wave-like change in the expression of AKT, GSK-3β, the 70S 6 kinase, mTOR was found with an increase in the size of the primary tumor. The presence of lymphogenous metastases and the level of regional lymph node involvement (N1–2) were associated with changes in the mRNA level of the 70S 6 kinase, PTEN, GSK-3β, and mTOR. As a result of neoadjuvant chemotherapy, the level of 4EBP1 mRNA increased by 2.6 times compared with that before treatment. At the same time, the low treatment efficacy was associated with an increase in PDK1 expression and a decrease in c-RAF expression. Conclusion. Molecular features of the development of colorectal cancer associated with changes in the expression of the components of the AKT / mTOR signaling pathway, depending on the locoregional prevalence of the tumor and the effectiveness of antitumor therapy, have been identified, which affects the prognosis of the disease.