Hlianko M. Individualization of combined treatment of patients with rectal cancer: molecular biological aspects

The dissertation is devoted to the assessment of improving the effectiveness of treatment of patients with rectal cancer using individualized regimens of chemotherapy which account the expression of markers associated with chemoresistance and the degree of tumor malignancy. The work has demonstrated the possibility of predicting the course of the disease in patients with rectal cancer by evaluating markers associated with the invasive potential of malignantly transformed cells (E-cadherin), and chemoresistance (ERCC1 and TopoII-α). The presence of only E-cadherin-positive cells in the tumor is asssociated with favorable prognosis by the means of the features of the disease course and patient’s survival, while the expression of Торо ІІα and ERCC1 in the tumor cells significantly worsens these indices. The study has revealed the high informativeness of certain combinations of phenotypic tumor cell markers, which indicate improvement (E-cadherin+/ERCC1-, E-cadherin+/ TopoII-α-) or worsening of the prognosis (E-cadherin-/ ERCC1+ and E-cadherin- /Торо ІІα+) of the disease course. The importance of comprehensive assessment of the expression status of E-cadherin, Торо ІІα and ERCC1 for the assignment of patients with rectal cancer to the group with increased risk of disease progression has been established. In addition, the feasibility of using individualized platinum-containing PCT regimens after radical surgical treatment of patients with rectal cancer with E-cadherin+/ERCC1–/Topo IIα– tumor cell phenotype was shown. The expression of at least one of the mentioned markers of chemoresistance increases the likelihood of deterioration in patient survival.