Signalling pathways involved in clinical responses to chemotherapy.

Chemotherapeutic agents and also radiotherapy trigger a series of signalling pathways in the cells that activate not only the apoptotic machinery but also cell survival pathways. Some of these pathways are also altered by genetic changes in specific type of tumours, and are different even between patients with the same tumour. Among these pathways, the majority of survival signals involve the ERK, AKT and nuclear factor-kappaB pathways and those related to cell death, which are driven mainly either by inhibition of such survival networks or by upregulation of the JNK/p38 MAP-kinases. Thus, the efficacy of a given chemotherapy appears as a result of the balance between cell death and survival pathways elicited in each individual tumour. Modulation of such survival pathways would help to increase the efficacy of chemotherapy. Different strategies based on conventional chemotherapy have been used in the past with modest success. The availability of new molecules such as inhibitors of survival pathways and the use of new technologies for the study of individual tumours would have a positive impact on patient survival.