Targeting ALK: Precision Medicine Takes On Drug Resistance

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Significance

Effective long-term treatment of ALK-rearranged cancers requires a mechanistic understanding of resistance to ALK TKIs so that rational therapies can be selected to combat resistance. This Review underscores the importance of serial biopsies in capturing the dynamic therapeutic vulnerabilities within a patient’s tumor, and offers a perspective into the complexity of on-target and off-target ALK TKI resistance mechanisms. Therapeutic strategies that can successfully overcome, and potentially prevent, these resistance mechanisms will have the greatest impact on patient outcome.

Acknowledgments

GRANT SUPPORT

This work was supported by grants from the National Cancer Institute (5R01CA164273, to ATS) and the National Foundation for Cancer Research (to ATS).

We apologize to the numerous colleagues whose important contributions could not be cited in this Review due to space constraints. This work was supported by grants from the National Cancer Institute (5R01CA164273, to A.T.S.), and the National Foundation for Cancer Research (to A.T.S), and by Be a Piece of the Solution and LungStrong.

Footnotes

Disclosures: GJR has served as a compensated consultant to Genentech/Roche, and his institution receives clinical research support from Pfizer, Novartis, Genentech/Roche, Ariad, and Millennium. ATS has served as a compensated consultant or received honoraria from Pfizer, Novartis, Genentech/Roche, Ariad, Ignyta, Daiichi-Sankyo, Taiho, Blueprint Medicines, Loxo, EMD Serono, and Foundation Medicine. JJL has no financial interests to declare.

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