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An early look at selective RET inhibitor resistance: new challenges and opportunities


Two RET inhibitors, selpercatinib and pralsetinib, recently received approval for the treatment of advanced RET fusion-positive lung cancer. Acquired resistance to these inhibitors will be a major challenge. We have shown that resistance can emerge due to recurrent RET kinase domain mutations and, in most cases, due to RET-independent mechanisms.

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J.J.L. and J.F.G. contributed to the writing and review of this manuscript.

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Correspondence to Justin F. Gainor.

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Competing interests

J.J.L. has served as a compensated consultant for Genentech, C4 Therapeutics, Blueprint Medicines, Nuvalent, and Turning Point Therapeutics; received honorarium and travel support from Pfizer; received institutional research funds from Hengrui Therapeutics, Turning Point Therapeutics, Neon Therapeutics, Relay Therapeutics, Bayer, Elevation Oncology, Roche, and Novartis; received CME funding from OncLive, MedStar Health, and Northwell Health. J.F.G. has served as a compensated consultant or received honoraria from Bristol-Myers Squibb, Genentech, Ariad/Takeda, Loxo/Lilly, Blueprint, Oncorus, Regeneron, Gilead, AstraZeneca, Pfizer, Incyte, Novartis, Merck, Mirati, EMD Serono, Glyde Bio, ImageAb, Agios, Amgen, and Array; research support from Novartis, Genentech/Roche, and Ariad/Takeda; institutional research support from Bristol-Myers Squibb, Tesaro, Moderna, Blueprint, Jounce, Array Biopharma, Merck, Adaptimmune, Novartis, and Alexo; and has an immediate family member who is an employee of Ironwood Pharmaceuticals.

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Lin, J.J., Gainor, J.F. An early look at selective RET inhibitor resistance: new challenges and opportunities. Br J Cancer 124, 1757–1758 (2021).

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