Invasion and metastasis of tumour cells resistant to chemotherapy.

Metastatic tumours resistant to chemotherapy are the major cause of the clinical failure in the treatment of malignant diseases. It is observed often that drugs active against primary tumours do not exhibit the same efficacy towards metastatic tumour cells having modified signaling pathways. Among cellular factors involved in the development of the metastatic potential of multidrug resistant tumour cells are some oncoproteins, antiapoptotic proteins, mutated suppressor proteins, integrins and CD44 receptor. It was also demonstrated that numerous chemotherapeutics have the effect on the emergence of the metastatic potential and multidrug resistance (MDR) phenomenon of tumour cells. The results of numerous studies suggest that genes involved in the development of MDR and metastatic phenotype of tumour cells are regulated by the same signaling pathways. They lead to the activation of transcription factors e.g. HIF-1α, NF-κB, Ets1 and AP-1 controlling the expression of genes involved in the development of the metastatic potential of multidrug resistant tumour cells. The identification of key cellular factors responsible for the emergence of the metastatic potential of MDR tumour cells could lead to the development of new efficient strategies for the treatment of metastatic tumours resistant to the conventional chemotherapy.