Rationale and clinical use of multitargeting anticancer agents.

Human solid tumors contain genetically distinct subpopulations of tumor cells that can be enriched under selective pressure of specific treatments. This heterogeneous nature reflects the dynamism of drug response and it represents a fundamental driver of resistance. Moreover, the complexity of cancer disease is increased by the activity of cross-talking, redundant signaling pathways, escape pathways and compensatory events, which triggers activation of secondary growth and survival. Broad multi-targeted approaches are requested to overcome a complex, heterogeneous, and dynamic disease such as cancer.