Vandetanib mechanism of action

Many targeted agents, such as anti-VEGF and anti-EGFR blockers, have not shown promise against mesothelioma, at least when used as single agents. However these same targeted agents might be effective when used in combination with chemotherapy or when used in a selected subpopulation. This study tested a variety of targeted agents together with cisplatinum-pemetrexed against 4 mesothelioma lines and found vandetanib, an inhibitor of EGFR/VEGFR2/RET, to be the most effective. Although the agent has multiple effects (see figure), the effect seemed to be explained by the effect on EGFR and was associated with suppression of phosphorylated Akt. The promise from this and other studies is that clinical trials using targeted agents may be designed in the future in subpopulations with evidence of dependence on that target (“addiction”). The targeted agent may then be effective on its own or by decreasing resistance to standard chemotherapy.

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