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CANCER THERAPY

Targeting drug-resistant mutations in ALK

Nature Cancer volume 3, pages 659–661 (2022)Cite this article

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Therapy resistance limits the clinical success of tyrosine kinase inhibitors (TKIs) in ALK-positive non-small cell lung cancer. A study now proposes a framework to identify compound resistance mutations to the lorlatinib TKI and provides structure-based drug design approaches to overcome resistance mediated by ALK(G1202R) or ALK(I1171N/S/T).

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Fig. 1: Mechanism of ALK compound mutations and inhibition by LA9 and LA7.

References

  1. Cohen, P. et al. Nat. Rev. Drug Discov. 20, 551–569 (2021).

    Article  CAS  Google Scholar 

  2. Settleman, J. Curr. Biol. 22, R43–R44 (2012).

    Article  CAS  Google Scholar 

  3. Shah, N. P. et al. Cancer Cell 2, 117–125 (2002).

    Article  CAS  Google Scholar 

  4. Yun, C. H. et al. Proc. Natl. Acad. Sci. USA 105, 2070–2075 (2008).

    Article  CAS  Google Scholar 

  5. O’Hare, T. et al. Cancer Cell 16, 401–412 (2009).

    Article  Google Scholar 

  6. Cross, D. A. et al. Cancer Discov. 4, 1046–1061 (2014).

    Article  CAS  Google Scholar 

  7. Gainor, J. F. et al. Cancer Discov. 6, 1118–1133 (2016).

    Article  CAS  Google Scholar 

  8. Yoda, S. et al. Cancer Discov. 8, 714–729 (2018).

    Article  CAS  Google Scholar 

  9. Shiba-Ishii, A. et al. Nat. Cancer https://doi.org/10.1038/s43018-022-00399-6 (2022).

  10. Fitzmaurice, C. et al. JAMA Oncol. 3, 524–548 (2017).

    Article  Google Scholar 

  11. Pikor, L. A. et al. Lung Cancer 82, 179–189 (2013).

    Article  Google Scholar 

  12. Sabir, S. R. et al. Cancers (Basel) 9, 118 (2017).

    Article  Google Scholar 

  13. Choo, J. R. & Soo, R. A. Expert Rev. Anticancer Ther. 20, 233–240 (2020).

    Article  CAS  Google Scholar 

  14. Bresler, S. C. et al. Cancer Cell 26, 682–694 (2014).

    Article  CAS  Google Scholar 

  15. Dagogo-Jack, I. & Shaw, A. T. Ann. Oncol. 27, iii42–iii50 (2016).

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Oncological Sciences, The Tisch Cancer Institute, Mount Sinai Centre for Therapeutic Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Liu He & Arvin C. Dar

  2. Department of Pharmacological Sciences, The Tisch Cancer Institute, Mount Sinai Centre for Therapeutic Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Liu He & Arvin C. Dar

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  1. Liu He
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  2. Arvin C. Dar
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Correspondence to Arvin C. Dar.

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Competing interests

A.C.D. is a founder, shareholder, consultant and advisory board member of Nested Therapeutics.

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He, L., Dar, A.C. Targeting drug-resistant mutations in ALK. Nat Cancer 3, 659–661 (2022). https://doi.org/10.1038/s43018-022-00390-1

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