We shall overcome (drug resistance) some day

The discovery of the involvement of defined molecular pathway(s) in tumor development and therapeutic targeting of such pathway(s) has revolutionised cancer treatment. More than 50 targeted therapeutic agents have been approved by the Food and Drug Administration (FDA) in the last two decades [1]. Unlike traditional cytotoxic treatments, targeted therapies rely on the dominant gene aberration that drives tumor growth and target only affected/malignant cells while sparing the healthy/non-malignant cells. However, although targeted therapies are highly effective and have improved patients survival, they are rarely curative [2]. In most cases, resistance against targeted therapies arises sooner or later. We now know that most tumors employ a highly complex and interconnected network of genetic alterations to drive their malignant growth and sustain survival, hence, single agent targeted therapies often result into modest long-term effects [3]. A number of mechanisms have been identified that mediate acquired (over time) resistance against the targeted therapies, such as point mutations that alter the binding of the drug to its target, activation of additional parallel or downstream signalling pathways (oncogene independent) as well as lineage changes of the tumor cells. Conversely, why some patients do not respond to the targeted therapies from the beginning (intrinsic resistance) is yet to be understood