Jan Styczyński, Lidia Gil

Znaczenie oporności na cytostatyki i jej markery
2007-02-01

Significance of cytostatic drug resistance and its markers. Clinical response to chemotherapy is related to: drug pharmacokinetics, cellular response to drug and growth potential of residual cancer cells. Cellular drug resistance is one of the main obstacles in oncological therapy. This phenomenon is defined as cellular insensitivity to drug reaching the cell, and is related to various mechanisms: primary and acquired, selective and pleiotropic, active and passive, which all play a role in cellular response. In hemato-oncology, better results of therapy are reached in children than in adults, in acute lymphoblastic leukemia (ALL) than in acute myeloid leukemia (AML). These differences are partially dependent on cellular drug resistance, which is also related to patients age, and biological properties of leukemic cells including cytogenetic and molecular aberrations. AML is considered a stem cell disease. Multidrug resistance proteins are preferentially expressed in leukemic stem cells, making this disease drug resistant. The most important clinical relevance of cellular sensitivity in acute leukemias was found for glucocorticoids, cytarabine, anthracyclines, vincristine and L-asparaginase. Study of new drugs show their potential to circumvent drug resistance. Current data suggest that cellular drug resistance is correlated with cytogenetic profile determined by microarray technology and has prognostic impact in childhood acute lymphoblastic leukemia.