Control of oncogenesis and cancer therapy resistance

Despite the combined action of surgery, radiotherapy and chemotherapy, the leading cause of death in cancer patients continues to be the acquired, or intrinsic, tumour resistance to therapy. Some of the genetic alterations that contribute to the malignant transformation are involved in maintaining cell survival under uncontrolled growth conditions. Chemotherapy agents, as well as radiotherapy, trigger a series of signalling pathways in the cells that activate not only the apoptotic machinery, but also cell-survival pathways. In this scenario, the efficacy of therapy is the result of balance between the apoptotic and the survival pathways activated in the tumour, and those elicited by the therapeutic agent. Apoptosis is one of the programmes usually altered in most cancers so as to guarantee tumour progression and, often, these alterations are responsible for therapy resistance, as well.