Combining EGFR Inhibitors With SHP2 Or LSD1 Inhibitors to Overcome Multidrug Resistance in Cancer

Future Medicinal ChemistryVol. 14, No. 8 EditorialCombining EGFR inhibitors with SHP2 or LSD1 inhibitors to overcome multidrug resistance in cancerHuiqing Zhang, Xinyu Yang, Yihui Song & Bin YuHuiqing ZhangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, ChinaSearch for more papers by this author, Xinyu YangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, ChinaSearch for more papers by this author, Yihui Song *Author for correspondence: Tel.: +86 0371 6778 1908; E-mail Address: songyihui@zzu.edu.cnhttps://orcid.org/0000-0001-7922-1209School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, ChinaSearch for more papers by this author & Bin Yu **Author for correspondence: E-mail Address: zzuyubin@hotmail.comhttps://orcid.org/0000-0002-7207-643XSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, ChinaSearch for more papers by this authorPublished Online:30 Mar 2022https://doi.org/10.4155/fmc-2021-0326AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: combination therapyEGFRLSD1multidrug resistanceSHP2References1. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 19(13), 3159–3167 (2000).Crossref, Medline, CAS, Google Scholar2. Lin Y, Wang X, Jin H. EGFR-TKI resistance in NSCLC patients--mechanisms and strategies. Am. J. Cancer Res. 4(5), 411–435 (2014).Medline, Google Scholar3. Pao W, Chmielecki J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat. Rev. Cancer 10(11), 760–774 (2010).Crossref, Medline, CAS, Google Scholar4. Normanno N, De Luca A, Bianco C et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366(1), 2–16 (2006).Crossref, Medline, CAS, Google Scholar5. Meng Y, Yu B, Huang H et al. Discovery of dosimertinib, a highly potent, selective, and orally efficacious deuterated EGFR targeting clinical candidate for the treatment of non-small-cell lung cancer. J. Med. Chem. 64(2), 925–937 (2021).Crossref, Medline, CAS, Google Scholar6. He P, Niu S, Wang S et al. Discovery of WS-157 as a highly potent, selective and orally active EGFR inhibitor. Acta Pharm. Sin. B 9(6), 1193–1203 (2019).Crossref, Medline, Google Scholar7. Herbst RS. Review of epidermal growth factor receptor biology. Int. J. Radiat. Oncol. Biol. Phys. 59(Suppl. 2), 21–26 (2004).Crossref, Medline, CAS, Google Scholar8. Tan D, Yom S, Tsao M et al. The international association for the study of lung cancer consensus statement on optimizing management of EGFR mutation-positive non-small cell lung cancer: status in 2016. J. Thorac. Oncol. 11(7), 946–963 (2016).Crossref, Medline, Google Scholar9. Ye L, Chen X, Zhou F. EGFR-mutant NSCLC: emerging novel drugs. Curr. Opin. Oncol. 33(1), 87–94 (2021).Crossref, Medline, CAS, Google Scholar10. Yuan S, Wang B, Dai Q et al. Discovery of new 4-indolyl quinazoline derivatives as highly potent and orally bioavailable P-glycoprotein inhibitors. J. Med. Chem. 64(19), 14895–14911 (2021).Crossref, Medline, CAS, Google Scholar11. Chen Y, Yang L, Qiao H et al. Discovery of new thieno[3,2-d]pyrimidine derivatives targeting EGFR (L858R/T790M) NSCLCs by the conformation constrained strategy. Eur. J. Med. Chem. 199, 112388 (2020).Crossref, Medline, CAS, Google Scholar12. Song Y, Zhao M, Zhang H, Yu B. Double-edged roles of protein tyrosine phosphatase SHP2 in cancer and its inhibitors in clinical trials. Pharmacol. Ther. 107966 (2021).Medline, Google Scholar13. Tang K, Jia YN, Yu B, Liu HM. Medicinal chemistry strategies for the development of protein tyrosine phosphatase SHP2 inhibitors and PROTAC degraders. Eur. J. Med. Chem. 204, 112657 (2020).Crossref, Medline, CAS, Google Scholar14. Liu C, Lu H, Wang H, Loo A et al. Combinations with allosteric shp2 inhibitor TNO155 to block receptor tyrosine kinase signaling. Clin. Cancer Res. 27(1), 342–354 (2021).Crossref, Medline, CAS, Google Scholar15. Sun Y, Meyers BA, Czako B et al. Allosteric SHP2 Inhibitor, IACS-13909, overcomes EGFR-dependent and EGFR-independent resistance mechanisms toward osimertinib. Cancer Res. 80(21), 4840–4853 (2020).Crossref, Medline, CAS, Google Scholar16. Song Y, Yang X, Yu B. Repurposing antidepressants for anticancer drug discovery. Drug Discov. Today S1359-6446(21), 00475-X, https://doi.org/10.1016/j.drudis.2021.10.019 (2021).Google Scholar17. Song Y, Zhang H, Yang X, Shi Y, Yu B. Annual review of lysine-specific demethylase 1 (LSD1/KDM1A) inhibitors in 2021. Eur. J. Med. Chem. 228, 114042 (2022).Crossref, Medline, CAS, Google Scholar18. Lu Y, Liu Y, Oeck S, Zhang GJ, Schramm A, Glazer PM. Hypoxia induces resistance to EGFR inhibitors in lung cancer cells via upregulation of FGFR1 and the MAPK pathway. Cancer Res. 80(21), 4655–4667 (2020).Crossref, Medline, CAS, Google Scholar19. Li Z, Suo F, Hu B et al. Identification of osimertinib (AZD9291) as a lysine specific demethylase 1 inhibitor. Bioorg. Chem. 84, 164–169 (2019).Crossref, Medline, CAS, Google Scholar20. Zheng M, Huo J, Gu X et al. Rational design and synthesis of novel dual PROTACs for simultaneous degradation of EGFR and PARP. J. Med. Chem. 64(11), 7839–7852 (2021).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByTargeting SHP2 for Cancer Treatment: Advances and Prospects4 January 2023Harnessing the cyclization strategy for new drug discoveryActa Pharmaceutica Sinica B, Vol. 12, No. 12 Vol. 14, No. 8 Follow us on social media for the latest updates Metrics Downloaded 207 times History Received 20 November 2021 Accepted 19 January 2022 Published online 30 March 2022 Published in print April 2022 Information© 2022 Newlands PressKeywordscombination therapyEGFRLSD1multidrug resistanceSHP2Financial & competing interests disclosureThis work is supported by the National Natural Science Foundation of China (no. 31900875 and 81973177). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download