engleski

Molecular-targeted approach to cancer therapy – the roles of p53 and p21WAF1/CIP1 genes

Although chemotherapy has been successfully used in the tumor treatment for more than 50 years, the outcome of the treatment is often limited due to the toxicity, rapid drug metabolism and occurrence of the resistance. It is well established nowadays that mutations in the cell cycle and death regulators are responsible not only for tumorigenesis but also for the resistance to antitumor drugs. Apoptosis is the best studied mechanism of the cellular response to therapy, but, on the other hand, it might also be permanent growth arrest or other, non-apoptotic mechanism, such as necrosis, senescence and “ mitotic catastrophe” . Elucidation of the factors that regulate treatment-induced non-apoptotic cell death mechanisms and the interdependency of death pathways will yield fresh insights into the evolution of cell-death programs and their potential for improving the efficacy and decreasing side effects of cancer therapy. One of the major regulators of the cell cycle, apoptosis and senescence is the p53 gene, being activated as the cell response to stress, and is the most frequently mutated gene in human tumors whose function loss might induce drug resistance. As majority of antitumor drugs damage DNA, this gene plays a crucial role in the response to therapy. Another very important cell-cycle regulator is p21WAF1/CIP1 whose activation is involved in the response to many chemotherapeutics, but its role is not completely elucidated ; it highly depends on cell type and cellular context. A detailed understanding of how anticancer agents induce cell death and how defects in death pathways promote resistance will contribute to the more effective and targeted cancer treatment. Besides, the improvement in gene delivery systems, and further adjuvant use of gene therapy with conventional chemotherapy will all lead to better clinical responses.

molecular targeted therapy, chemotherapy, apoptosis, senescence, p53, p21WAF1/CIP1

Zbornik je uvršten u Current Contents.