1. bookVolumen 72 (2022): Heft 1 (March 2022)
28 Feb 2007
4 Hefte pro Jahr
Uneingeschränkter Zugang

Update on glasdegib in acute myeloid leukemia – broadening horizons of Hedgehog pathway inhibitors

Online veröffentlicht: 30 Aug 2021
Volumen & Heft: Volumen 72 (2022) - Heft 1 (March 2022)
Seitenbereich: 9 - 34
Akzeptiert: 26 Jan 2021
28 Feb 2007
4 Hefte pro Jahr

1. C. Nüsslein-Volhard and E. Wieschaus, Mutations affecting segment number and polarity in Drosophila, Nature 287 (1980) 795–801; https://doi.org/10.1038/287795a010.1038/287795a0 Search in Google Scholar

2. R. Machold, S. Hayashi, M. Rutlin, M. D. Muzumdar, S. Nery, J. G. Corbin, A. Gritli-Linde, T. Dellovade, J. A. Porter, L. L. Rubin, H. Dudek, A. P. McMahon and G. Fishell, Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches, Neuron 39 (2003) 937–950; https://doi.org/10.1016/s0896-6273(03)00561-010.1016/S0896-6273(03)00561-0 Search in Google Scholar

3. C. Torroja, N. Gorfinkiel and I. Guerrero, Mechanisms of Hedgehog gradient formation and interpretation, J. Neurobiol. 64 (2005) 334–356; https://doi.org/10.1002/neu.2016810.1002/neu.2016816041759 Search in Google Scholar

4. M. Varjosalo and J. Taipale, Hedgehog: functions and mechanisms, Genes Dev. 22 (2008) 2454–2472; https://doi.org/10.1101/gad.169360810.1101/gad.169360818794343 Search in Google Scholar

5. E. Pak and R. A. Segal, Hedgehog signal transduction: Key players, oncogenic drivers, and cancer therapy, Dev. Cell 38 (2016) 333–344; https://doi.org/10.1016/j.devcel.2016.07.02610.1016/j.devcel.2016.07.026501730727554855 Search in Google Scholar

6. D. M. Stone, M. Hynes, M. Armanini, T. A. Swanson, Q. Gu, R. L. Johnson, M. P. Scott, D. Pennica, A. Goddard, H. Phillips, M. Noll, J. E. Hooper, F. de Sauvage and A. Rosenthal, The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog, Nature 384 (1996) 129–134; https://doi.org/10.1038/384129a010.1038/384129a08906787 Search in Google Scholar

7. M. Kasper, H. Schnidar, G. W. Neill, M. Hanneder, S. Klingler, L. Blaas, C. Schmid, C. Hauser-Kronberger, G. Regl, M. P. Philpott and F. Aberger, Selective modulation of Hedgehog/GLI target gene expression by epidermal growth factor signaling in human keratinocytes, Mol. Cell. Biol. 26 (2006) 6283–6298; https://doi.org/10.1128/MCB.02317-0510.1128/MCB.02317-05159281616880536 Search in Google Scholar

8. I. D. Louro, E. C. Bailey, X. Li, L. S. South, P. R. McKie-Bell, B. K. Yoder, C. C. Huang, M. R. Johnson, A. E. Hill, R. L. Johnson and J. M. Ruppert, Comparative gene expression profile analysis of GLI and c-MYC in an epithelial model of malignant transformation, Cancer Res. 62 (2002) 5867–5873. Search in Google Scholar

9. L. E. C. Wanshura, K. E. Galvin, H. Ye, M. E. Fernandez-Zapico and C. Wetmore, Sequential activation of Snail1 and N-Myc modulates Sonic Hedgehog-induced transformation of neural cells, Cancer Res. 71 (2011) 5336–5345; https://doi.org/10.1158/0008-5472.CAN-10-263310.1158/0008-5472.CAN-10-2633341268921646478 Search in Google Scholar

10. M. Merchant, F. F. Vajdos, M. Ultsch, H. R. Maun, U. Wendt, J. Cannon, W. Desmarais, R. A. Lazarus, A. M. de Vos and F. J. de Sauvage, Suppressor of Fused regulates Gli activity through a dual binding mechanism, Mol. Cell. Biol. 24 (2004) 8627–8641; https://doi.org/10.1128/MCB.24.19.8627-8641.200410.1128/MCB.24.19.8627-8641.200451676315367681 Search in Google Scholar

11. A. M. Skoda, D. Simovic, V. Karin, V. Kardum, S. Vranic and L. Serman, The role of the Hedgehog signaling pathway in cancer: A comprehensive review, Bosn. J. Basic Med. Sci. 18 (2018) 8–20; https://doi.org/10.17305/bjbms.2018.275610.17305/bjbms.2018.2756582667829274272 Search in Google Scholar

12. C. Zhao, A. Chen, C. H. Jamieson, M. Fereshteh, A. Abrahamsson, J. Blum, H. Y. Kwon, J. Kim, J. P. Chute, D. Rizzieri, M. Munchhof, T. VanArsdale, P. A. Beachy and T. Reya, Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia, Nature 458 (2009) 776–779; https://doi.org/10.1038/nature0773710.1038/nature07737294623119169242 Search in Google Scholar

13. N. Bhagwat, M. D. Keller, R. K. Rampal, K. Shank, E. de Stanchina, K. Rose, D. Amakye and R. L. Levine, Improved efficacy of combination of JAK2 and Hedgehog inhibitors in myelofibrosis, Blood 122 (2013) 666–666; https://doi.org/10.1182/blood.V122.21.666.66610.1182/blood.V122.21.666.666 Search in Google Scholar

14. J. M. Xavier-Ferrucio, F. V. Pericole, M. R. Lopes, P. Latuf-Filho, K. S. A. Barcellos, A. I. Dias, P. de M. Campos, F. Traina, J. Vassallo, S. T. O. Saad and P. Favaro, Abnormal Hedgehog pathway in myelodysplastic syndrome and its impact on patients’ outcome, Haematologica 100 (2015) e491-493; https://doi.org/10.3324/haematol.2015.12404010.3324/haematol.2015.124040466633826294731 Search in Google Scholar

15. M. Kobune, R. Takimoto, K. Murase, S. Iyama, T. Sato, S. Kikuchi, Y. Kawano, K. Miyanishi, Y. Sato, Y. Niitsu and J. Kato, Drug resistance is dramatically restored by hedgehog inhibitors in CD34+ leukemic cells, Cancer Sci. 100 (2009) 948–955; https://doi.org/10.1111/j.1349-7006.2009.01111.x10.1111/j.1349-7006.2009.01111.x19245435 Search in Google Scholar

16. B. Long, L.-X. Wang, F.-M. Zheng, S.-P. Lai, D.-R. Xu, Y. Hu, D.-J. Lin, X.-Z. Zhang, L. Dong, Z.-J. Long, X.-Z. Tong and Q. Liu, Targeting GLI1 suppresses cell growth and enhances chemosensitivity in CD34+ enriched acute myeloid leukemia progenitor cells, Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 38 (2016) 1288–1302; https://doi.org/10.1159/00044307510.1159/00044307527008269 Search in Google Scholar

17. K. C. S. Queiroz, R. R. Ruela-de-Sousa, G. M. Fuhler, H. L. Aberson, C. V. Ferreira, M. P. Peppelen-bosch and C. A. Spek, Hedgehog signaling maintains chemoresistance in myeloid leukemic cells, Oncogene 29 (2010) 6314–6322; https://doi.org/10.1038/onc.2010.37510.1038/onc.2010.37520802532 Search in Google Scholar

18. H. A. Zahreddine, B. Culjkovic-Kraljacic, S. Assouline, P. Gendron, A. A. Romeo, S. J. Morris, G. Cormack, J. B. Jaquith, L. Cerchietti, E. Cocolakis, A. Amri, J. Bergeron, B. Leber, M. W. Becker, S. Pei, C. T. Jordan, W. H. Miller and K. L. B. Borden, The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation, Nature 511 (2014) 90–93; https://doi.org/10.1038/nature1328310.1038/nature13283413805324870236 Search in Google Scholar

19. K. Huang, B. Ding, Q. Zhong, X. Jiang, X. Li, Z. Wang and F. Y. Meng, Hh/IGF-1R/PI3K/Akt/MRP1 pathway induce refractory acute myeloid leukemia and its targeting therapy, Blood 124 (2014) 3612–3612; https://doi.org/10.1182/blood.V124.21.3612.361210.1182/blood.V124.21.3612.3612 Search in Google Scholar

20. F. Meng, X. Li, B. Ding, K. Huang, Q. Zhu, F. Chen and Y. Zhu, Molecular mechanism and optimal treatment strategy in acute myeloid leukemia with resistance to drugs and radiation by NVPLED225, Blood 126 (2015) 3691–3691; https://doi.org/10.1182/blood.V126.23.3691.369110.1182/blood.V126.23.3691.3691 Search in Google Scholar

21. X. Li, F. Chen, Q. Zhu, B. Ding, Q. Zhong, K. Huang, X. Jiang, Z. Wang, C. Yin, Y. Zhu, Z. Li and F. Meng, Gli-1/PI3K/AKT/NF-kB pathway mediates resistance to radiation and is a target for reversion of responses in refractory acute myeloid leukemia cells, Oncotarget 7 (2016) 33004–33015; https://doi.org/10.18632/oncotarget.884410.18632/oncotarget.8844507807027105509 Search in Google Scholar

22. J. Bariwal, V. Kumar, Y. Dong and R. I. Mahato, Design of Hedgehog pathway inhibitors for cancer treatment, Med. Res. Rev. 39 (2019) 1137–1204; https://doi.org/10.1002/med.2155510.1002/med.21555671458530484872 Search in Google Scholar

23. R. Tibes, A. Al-Kali, G. R. Oliver, D. H. Delman, N. Hansen, K. Bhagavatula, J. Mohan, F. Rakhshan, T. Wood, J. M. Foran, R. A. Mesa and J. M. Bogenberger, The Hedgehog pathway as targetable vulnerability with 5-azacytidine in myelodysplastic syndrome and acute myeloid leukemia, J. Hematol. Oncol. 8 (2015) 114; https://doi.org/10.1186/s13045-015-0211-810.1186/s13045-015-0211-8461536326483188 Search in Google Scholar

24. D. A. Irvine, B. Zhang, R. Kinstrie, A. Tarafdar, H. Morrison, V. L. Campbell, H. A. Moka, Y. Ho, C. Nixon, P. W. Manley, H. Wheadon, J. R. Goodlad, T. L. Holyoake, R. Bhatia and M. Copland, Deregulated Hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia, Sci. Rep. 6 (2016) 25476; https://doi.org/10.1038/srep2547610.1038/srep25476486061927157927 Search in Google Scholar

25. J. E. Cortes, R. Gutzmer, M. W. Kieran and J. A. Solomon, Hedgehog signaling inhibitors in solid and hematological cancers, Cancer Treat. Rev. 76 (2019) 41–50; https://doi.org/10.1016/j.ctrv.2019.04.00510.1016/j.ctrv.2019.04.00531125907 Search in Google Scholar

26. J. E. Cortes, F. H. Heidel, A. Hellmann, W. Fiedler, B. D. Smith, T. Robak, P. Montesinos, D. A. Pollyea, P. DesJardins, O. Ottmann, W. W. Ma, M. N. Shaik, A. D. Laird, M. Zeremski, A. O’Connell, G. Chan and M. Heuser, Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome, Leukemia 33 (2019) 379–389; https://doi.org/10.1038/s41375-018-0312-910.1038/s41375-018-0312-9636549230555165 Search in Google Scholar

27. S. M. Hoy, Glasdegib: First global approval, Drugs 79 (2019) 207–213; https://doi.org/10.1007/s40265-018-1047-710.1007/s40265-018-1047-730666593 Search in Google Scholar

28. K. J. Norsworthy, K. By, S. Subramaniam, L. Zhuang, P. L. Del Valle, D. Przepiorka, Y.-L. Shen, C. M. Sheth, C. Liu, R. Leong, K. B. Goldberg, A. T. Farrell and R. Pazdur, FDA approval summary: glasdegib for newly diagnosed acute myeloid leukemia, Clin. Cancer Res. 25 (2019) 6021–6025; https://doi.org/10.1158/1078-0432.CCR-19-036510.1158/1078-0432.CCR-19-036531064779 Search in Google Scholar

29. E. Estey, J. E. Karp, A. Emadi, M. Othus and R. P. Gale, Recent drug approvals for newly diagnosed acute myeloid leukemia: gifts or a Trojan horse?, Leukemia 34 (2020) 671–681; https://doi.org/10.1038/s41375-019-0704-510.1038/s41375-019-0704-531915366 Search in Google Scholar

30. T. Hilal, Progress in acute myeloid leukaemia: small molecular inhibitors with small benefits, Ecancermedicalscience 14 (2020); https://doi.org/10.3332/ecancer.2020.101510.3332/ecancer.2020.1015710534032256698 Search in Google Scholar

31. A. Fiorentini, D. Capelli, F. Saraceni, D. Menotti, A. Poloni and A. Olivieri, The time has come for targeted therapies for AML: lights and shadows, Oncol. Ther. 8 (2020) 13–32; https://doi.org/10.1007/s40487-019-00108-x10.1007/s40487-019-00108-x735999632700072 Search in Google Scholar

32. M. J. Munchhof, Q. Li, A. Shavnya, G. V. Borzillo, T. L. Boyden, C. S. Jones, S. D. LaGreca, L. Martinez-Alsina, N. Patel, K. Pelletier, L. A. Reiter, M. D. Robbins and G. T. Tkalcevic, Discovery of PF-04449913, a potent and orally bioavailable inhibitor of Smoothened, ACS Med. Chem. Lett. 3 (2012) 106–111; https://doi.org/10.1021/ml200242310.1021/ml2002423 Search in Google Scholar

33. L. Rubin, O. M. Guicherit, S. Price and E. A. Boyd, Mediators of Hedgehog signaling pathways, compositions and uses related thereto; Retrieved from https://patents.google.com/patent/WO2003011219A2/en Search in Google Scholar

34. A. J. Jackson-Fisher, M. J. McMahon, J. Lam, C. Li, L. D. Engstrom, K. Tsaparikos, D. J. Shields, D. D. Fang, M. E. Lira, Z. Zhu, M. D. Robbins, R. Schwab, M. J. Munchhof and T. VanArsdale, Abstract 4504: PF-04449913, a small molecule inhibitor of Hedgehog signaling, is effective in inhibiting tumor growth in preclinical models, Exp. Mol. Ther. (pp. 4504–4504). Presented at the Proceedings: AACR 102nd Annual Meeting 2011 - Apr 2-6, 2011; Orlando, FL, American Association for Cancer Research; https://doi.org/10.1158/1538-7445.AM2011-450410.1158/1538-7445.AM2011-4504 Search in Google Scholar

35. G. Martinelli, V. G. Oehler, C. Papayannidis, R. Courtney, M. N. Shaik, X. Zhang, A. O’Connell, K. R. McLachlan, X. Zheng, J. Radich, M. Baccarani, H. M. Kantarjian, W. J. Levin, J. E. Cortes and C. Jamieson, Treatment with PF-04449913, an oral Smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study, Lancet Haematol. 2 (2015) e339-346; https://doi.org/10.1016/S2352-3026(15)00096-410.1016/S2352-3026(15)00096-4 Search in Google Scholar

36. A. J. Wagner, W. A. Messersmith, M. N. Shaik, S. Li, X. Zheng, K. R. McLachlan, R. Cesari, R. Courtney, W. J. Levin and A. B. El-Khoueiry, A phase I study of PF-04449913, an oral Hedgehog inhibitor, in patients with advanced solid tumors, Clin. Cancer Res. 21 (2015) 1044–1051; https://doi.org/10.1158/1078-0432.CCR-14-111610.1158/1078-0432.CCR-14-111625388167 Search in Google Scholar

37. G. Giordani, M. Barraco, A. Giangrande, G. Martinelli, V. Guadagnuolo, G. Simonetti, G. Perini and R. Bernardoni, The human Smoothened inhibitor PF-04449913 induces exit from quiescence and loss of multipotent Drosophila hematopoietic progenitor cells, Oncotarget 7 (2016) 55313–55327; https://doi.org/10.18632/oncotarget.1087910.18632/oncotarget.10879534241927486815 Search in Google Scholar

38. M. Copland, A. Hamilton, L. J. Elrick, J. W. Baird, E. K. Allan, N. Jordanides, M. Barow, J. C. Mountford and T. L. Holyoake, Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction, Blood 107 (2006) 4532–4539; https://doi.org/10.1182/blood-2005-07-294710.1182/blood-2005-07-294716469872 Search in Google Scholar

39. X. Jiang, Y. Zhao, C. Smith, M. Gasparetto, A. Turhan, A. Eaves and C. Eaves, Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies, Leukemia 21 (2007) 926–935; https://doi.org/10.1038/sj.leu.240460910.1038/sj.leu.240460917330101 Search in Google Scholar

40. C. Dierks, R. Beigi, G.-R. Guo, K. Zirlik, M. R. Stegert, P. Manley, C. Trussell, A. Schmitt-Graeff, K. Landwerlin, H. Veelken and M. Warmuth, Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation, Cancer Cell 14 (2008) 238–249; https://doi.org/10.1016/j.ccr.2008.08.00310.1016/j.ccr.2008.08.00318772113 Search in Google Scholar

41. N. Fukushima, Y. Minami, S. Kakiuchi, Y. Kuwatsuka, F. Hayakawa, C. Jamieson, H. Kiyoi and T. Naoe, Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells, Cancer Sci. 107 (2016) 1422–1429; https://doi.org/10.1111/cas.1301910.1111/cas.13019508466427461445 Search in Google Scholar

42. A. Schairer, A. Shih, I. Geron, T. Reya, W. J. Levin, T. Van Arsdale and C. Jamieson, Human blast crisis leukemia stem cell inhibition with a novel Smoothened antagonist., Blood 116 (2010) 1223–1223; https://doi.org/10.1182/blood.V116.21.1223.122310.1182/blood.V116.21.1223.1223 Search in Google Scholar

43. A. Y. Shih, A. Schairer, C. L. Barrett, I. Geron, A. C. Court Recart, D. Goff, S. Prashad, J. Wu, Q. Jiang, J. Gotlib, L. Balaian, M. D. Minden, H. Leu, R. Wall, W. Ma, K. Shazand, J. D. McPherson, S. M. Kornblau, I. Deichaite, M. Pu, L. Bao, G. Martinelli, T. Reya, S. R. Morris, T. van Arsdale, T. J. Hudson, K. Messer, H. Mikkola, W. J. Levin, K. A. Frazer, A. Sadarangani and C. Jamieson, Cycling toward leukemia stem cell elimination with a selective Sonic Hedgehog antagonist, Blood 118 (2011) 3776–3776; https://doi.org/10.1182/blood.V118.21.3776.377610.1182/blood.V118.21.3776.3776 Search in Google Scholar

44. P. Chaudhry, M. Singh, T. J. Triche, M. Guzman and A. A. Merchant, GLI3 repressor determines Hedgehog pathway activation and is required for response to SMO antagonist glasdegib in AML, Blood 129 (2017) 3465–3475; https://doi.org/10.1182/blood-2016-05-71858510.1182/blood-2016-05-718585549208928487292 Search in Google Scholar

45. A. Jackson-Fisher, P. Whalen, M. Elliott, M. McMahon, E. Chen, X. Zheng, M. Ozeck, D. Huang, P. Lira, J. Lee, C. Zhang, J. Lam, M. Spilker, S. Deng, P. Lappin, P. Venne, C. Heinlein, A. Schairer, K. McLachlan and T. VanArsdale, Abstract 1958: Interrogating Hedgehog pathway and smoothened inhibition by PF-04449913 in patient-derived acute myeloid leukemia models, Tumor Biol. (pp. 1958–1958). Presented at the Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA, American Association for Cancer Research; https://doi.org/10.1158/1538-7445.AM2014-195810.1158/1538-7445.AM2014-1958 Search in Google Scholar

46. A. Sadarangani, G. Pineda, K. M. Lennon, H.-J. Chun, A. Shih, A. E. Schairer, A. C. Court, D. J. Goff, S. L. Prashad, I. Geron, R. Wall, J. D. McPherson, R. A. Moore, M. Pu, L. Bao, A. Jackson-Fisher, M. Munchhof, T. VanArsdale, T. Reya, S. R. Morris, M. D. Minden, K. Messer, H. K. A. Mikkola, M. A. Marra, T. J. Hudson and C. H. M. Jamieson, GLI2 inhibition abrogates human leukemia stem cell dormancy, J. Transl. Med. 13 (2015) 98; https://doi.org/10.1186/s12967-015-0453-910.1186/s12967-015-0453-9441437525889765 Search in Google Scholar

47. C. Jamieson, J. E. Cortes, V. Oehler, M. Baccarani, H. M. Kantarjian, C. Papayannidis, K. N. Rice, X. Zhang, N. Shaik, R. Courtney, W. J. Levin and G. Martinelli, Phase 1 Dose-escalation study of PF-04449913, an oral Hedgehog (Hh) inhibitor, in patients with select hematologic malignancies, Blood 118 (2011) 424–424; https://doi.org/10.1182/blood.V118.21.424.42410.1182/blood.V118.21.424.424 Search in Google Scholar

48. V. Guadagnuolo, C. Papayannidis, I. Iacobucci, S. Durante, C. Terragna, E. Ottaviani, M. C. Abbenante, F. Cattina, S. Soverini, B. Lama, L. Toni, W. J. Levin, R. Courtney, C. Baldazzi, A. Curti, M. Baccarani, C. Jamieson, J. E. Cortes, V. Oehler, K. McLachlan, T. Van Arsdale and G. Martinelli, Gas1 and Kif27 genes are strongly up-regulated biomarkers of Hedgehog inhibition (PF-04449913) on leukemia stem cells in phase I acute myeloid leukemia and chronic myeloid leukemia treated patients, Blood 118 (2011) 1535–1535; https://doi.org/10.1182/blood.V118.21.1535.153510.1182/blood.V118.21.1535.1535 Search in Google Scholar

49. C. Papayannidis, V. Guadagnuolo, I. Iacobucci, S. Durante, C. Terragna, E. Ottaviani, M. C. Abbenante, F. Cattina, S. Soverini, B. Lama, L. Toni, W. J. Levin, R. Courtney, C. Baldazzi, A. Curti, M. Baccarani, C. Jamieson, J. E. Cortes, V. Oehler, K. McLachlan, T. Van Arsdale and G. Martinelli, PF-04449913 reverts multi drug resistance (MDR) by a strong down-regulation of ABCA2 and BCL2 on leukemia stem cells in phase I acute myeloid leukemia and chronic myeloid leukemia treated patients, Blood 118 (2011) 1429–1429; https://doi.org/10.1182/blood.V118.21.1429.142910.1182/blood.V118.21.1429.1429 Search in Google Scholar

50. Y. Minami, H. Minami, T. Miyamoto, G. Yoshimoto, Y. Kobayashi, W. Munakata, Y. Onishi, M. Kobayashi, M. Ikuta, G. Chan, A. Woolfson, C. Ono, M. N. Shaik, Y. Fujii, X. Zheng and T. Naoe, Phase I study of glasdegib (PF-04449913), an oral Smoothened inhibitor, in Japanese patients with select hematologic malignancies, Cancer Sci. 108 (2017) 1628–1633; https://doi.org/10.1111/cas.1328510.1111/cas.13285554350728556364 Search in Google Scholar

51. M. R. Savona, D. A. Pollyea, W. Stock, V. G. Oehler, M. A. Schroeder, J. Lancet, J. McCloskey, H. M. Kantarjian, W. W. Ma, M. N. Shaik, A. D. Laird, M. Zeremski, A. O’Connell, G. Chan and J. E. Cortes, Phase Ib study of glasdegib, a Hedgehog pathway inhibitor, in combination with standard chemotherapy in patients with AML or high-risk MDS, Clin. Cancer Res. 24 (2018) 2294–2303; https://doi.org/10.1158/1078-0432.CCR-17-282410.1158/1078-0432.CCR-17-282429463550 Search in Google Scholar

52. U. Borate, B. D. Smith, S. Gore, A. M. Zeidan, M. R. Savona, M. L. Savoie, N. Zhu, D. Breems, X. Zhang, M. N. Shaik, A. Rampersad, G. Chan, A. Woolfson and M. A. Sekeres, Phase 1B study of glasdegib (PF-04449913) in combination with azacitidine in patients with higher risk myelodysplasic syndrome, oligoblastic acute myeloid leukemia, or chronic myelomonocytic leukemia [abstract no. P255], Haematologica 101 (Suppl 1) (2016) 73–74. Search in Google Scholar

53. M. A. Sekeres, M. W. Schuster, M. Joris, J. Krauter, J. A. Maertens, E. Gyan, T. Kovacsovics, A. Verma, P. Vyas, E. S. Wang, W. Wendy Ma, M. Zeremski, A. Kudla, G. Chan and A. M. Zeidan, A phase 1b study of glasdegib in combination with azacitidine in patients with untreated higher-risk myelodysplastic syndromes, acute myeloid leukemia, and chronic myelomonocytic leukemia, Blood 134 (2019) 177–177; https://doi.org/10.1182/blood-2019-12405010.1182/blood-2019-124050 Search in Google Scholar

54. A. M. Zeidan, M. Schuster, M. Joris, J. Krauter, J. Maertens, E. Gyan, T. Kovacsovics, A. Verma, P. Vyas, E. S. Wang, W. Ma, M. Zeremski, A. Kudla, G. Chan and M. A. Sekeres, Glasdegib in combination with azacitidine (AZA) in patients (pts) with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML): Effects on marrow recovery and transfusion independence, J. Clin. Oncol. 38 (2020) 7526–7526; https://doi.org/10.1200/JCO.2020.38.15_suppl.752610.1200/JCO.2020.38.15_suppl.7526 Search in Google Scholar

55. E. S. Wang, T. Bell, A. M. Zeidan, H. Bhattacharyya, A. Kudla, G. Chan and M. A. Sekeres, Health-related quality of life (HRQoL) in patients with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) receiving glasdegib + azacitidine (AZA), J. Clin. Oncol. 38 (2020) 7527–7527; https://doi.org/10.1200/JCO.2020.38.15_suppl.752710.1200/JCO.2020.38.15_suppl.7527 Search in Google Scholar

56. A. T. Gerds, T. Tauchi, E. Ritchie, M. Deininger, C. Jamieson, R. Mesa, M. Heaney, N. Komatsu, H. Minami, Y. Su, N. Shaik, X. Zhang, C. DiRienzo, M. Zeremski, G. Chan and M. Talpaz, Phase 1/2 trial of glasdegib in patients with primary or secondary myelofibrosis previously treated with ruxolitinib, Leuk. Res. 79 (2019) 38–44; https://doi.org/10.1016/j.leukres.2019.02.01210.1016/j.leukres.2019.02.012814898530849661 Search in Google Scholar

57. J. E. Cortes, B. Douglas Smith, E. S. Wang, A. Merchant, V. G. Oehler, M. Arellano, D. J. DeAngelo, D. A. Pollyea, M. A. Sekeres, T. Robak, W. W. Ma, M. Zeremski, M. Naveed Shaik, A. Douglas Laird, A. O’Connell, G. Chan and M. A. Schroeder, Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results, Am. J. Hematol. 93 (2018) 1301–1310; https://doi.org/10.1002/ajh.2523810.1002/ajh.25238622110230074259 Search in Google Scholar

58. H. Kantarjian, Y. Oki, G. Garcia-Manero, X. Huang, S. O’Brien, J. Cortes, S. Faderl, C. Bueso-Ramos, F. Ravandi, Z. Estrov, A. Ferrajoli, W. Wierda, J. Shan, J. Davis, F. Giles, H. I. Saba and J.-P. J. Issa, Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia, Blood 109 (2007) 52–57; https://doi.org/10.1182/blood-2006-05-02116210.1182/blood-2006-05-02116216882708 Search in Google Scholar

59. S. Thépot, R. Itzykson, V. Seegers, C. Recher, E. Raffoux, B. Quesnel, J. Delaunay, T. Cluzeau, A. Marfaing Koka, A. Stamatoullas, M.-P. Chaury, C. Dartigeas, S. Cheze, A. Banos, P. Morel, I. Plan-tier, A.-L. Taksin, J. P. Marolleau, C. Pautas, X. Thomas, F. Isnard, B. Beve, Y. Chait, A. Guerci, N. Vey, F. Dreyfus, L. Ades, N. Ifrah, H. Dombret, P. Fenaux and C. Gardin, Azacitidine in untreated acute myeloid leukemia: a report on 149 patients: azacitidine in frontline AML, Am. J. Hematol. 89 (2014) 410–416; https://doi.org/10.1002/ajh.2365410.1002/ajh.2365424375487 Search in Google Scholar

60. H. Dombret, J. F. Seymour, A. Butrym, A. Wierzbowska, D. Selleslag, J. H. Jang, R. Kumar, J. Cavenagh, A. C. Schuh, A. Candoni, C. Récher, I. Sandhu, T. Bernal del Castillo, H. K. Al-Ali, G. Martinelli, J. Falantes, R. Noppeney, R. M. Stone, M. D. Minden, H. McIntyre, S. Songer, L. M. Lucy, C. L. Beach and H. Döhner, International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts, Blood 126 (2015) 291–299; https://doi.org/10.1182/blood-2015-01-62166410.1182/blood-2015-01-621664450494525987659 Search in Google Scholar

61. S. M. Luger, Acute myeloid leukemia: how to treat the fit patient over age 75?, Best Pract. Res. Clin. Haematol. 32 (2019) 101105; https://doi.org/10.1016/j.beha.2019.10110510.1016/j.beha.2019.10110531779985 Search in Google Scholar

62. J. E. Cortes, A. Merchant, C. Jamieson, D. A. Pollyea, M. Heuser, G. Chan, P. Wang, K. A. Ching, J. Johnson and T. O’Brien, Biomarkers of overall survival and response to glasdegib and intensive or non-intensive chemotherapy in patients with acute myeloid leukemia, Blood 132 (2018) 1429–1429; https://doi.org/10.1182/blood-2018-99-11123910.1182/blood-2018-99-111239 Search in Google Scholar

63. K. A. Ching, D. Huang, K. Wang, M. Ozeck, P. Lira, J. Gao, J. Bienkowska, P. Rejto, J. Hardwick, T. O’Brien and G. Chan, Analysis of mutations associated with response to glasdegib in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), Clin. Res. Clin. Trials (pp. LB-215–LB-215). Presented at the Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL, American Association for Cancer Research.; https://doi.org/10.1158/1538-7445.AM2018-LB-21510.1158/1538-7445.AM2018-LB-215 Search in Google Scholar

64. S. Lin, N. Shaik, G. Chan, J. E. Cortes and A. Ruiz-Garcia, An evaluation of overall survival in patients with newly diagnosed acute myeloid leukemia and the relationship with glasdegib treatment and exposure, Cancer Chemother. Pharmacol. 86 (2020) 451–459; https://doi.org/10.1007/s00280-020-04132-x10.1007/s00280-020-04132-x Search in Google Scholar

65. H. Döhner, M. Lübbert, W. Fiedler, L. Fouillard, A. Haaland, J. M. Brandwein, S. Lepretre, O. Reman, P. Turlure, O. G. Ottmann, C. Müller-Tidow, A. Krämer, E. Raffoux, K. Döhner, R. F. Schlenk, F. Voss, T. Taube, H. Fritsch and J. Maertens, Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy, Blood 124 (2014) 1426–1433.; https://doi.org/10.1182/blood-2014-03-56055710.1182/blood-2014-03-560557 Search in Google Scholar

66. A. K. Burnett, N. Russell, R. K. Hills, N. Panoskaltsis, A. Khwaja, C. Hemmaway, P. Cahalin, R. E. Clark and D. Milligan, A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia, Leukemia 29 (2015) 1312–1319; https://doi.org/10.1038/leu.2015.3810.1038/leu.2015.38 Search in Google Scholar

67. M. Heiblig, M. Elhamri, I. Tigaud, A. Plesa, F. Barraco, H. Labussière, S. Ducastelle, M. Michallet, F. Nicolini, C. Plesa, E. Wattel, G. Salles and X. Thomas, Treatment with low-dose cytarabine in elderly patients (age 70 years or older) with acute myeloid leukemia: a single institution experience, Mediterr. J. Hematol. Infect. Dis. 8 (2016) 2016009; https://doi.org/10.4084/mjhid.2016.00910.4084/mjhid.2016.009 Search in Google Scholar

68. A. T. Fathi, Glasdegib with low-dose cytarabine: a new upfront option for the vulnerable AML patient, Clin. Cancer Res. 25 (2019) 6015–6017; https://doi.org/10.1158/1078-0432.CCR-19-198610.1158/1078-0432.CCR-19-1986 Search in Google Scholar

69. C. Papayannidis, B. D. Smith, M. Heuser, P. Montesinos, M. A. Sekeres, A. Oriol, G. Schiller, A. Candoni, C. Jamieson, C. J. Hoang, W. W. Ma, M. Zeremski, A. O’Connell, G. Chan and J. E. Cortes, Low-dose cytarabine with or without glasdegib in newly diagnosed patients with acute myeloid leukemia: long-term analysis of a phase 2 randomized trial, Clin. Lymphoma Myeloma Leuk. 19 (2019) S228–S229; https://doi.org/10.1016/j.clml.2019.07.11110.1016/j.clml.2019.07.111 Search in Google Scholar

70. M. Heuser, W. Fiedler, M. A. Sekeres, P. Montesinos, B. Leber, A. Merchant, C. Papayannidis, J. A. Pérez-Simón, C. J. Hoang, W. Wendy Ma, M. Zeremski, A. O’Connell, G. Chan and J. E. Cortes, Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase 2 randomized trial, Clin. Lymphoma Myeloma Leuk. 19 (2019) S231–S231; https://doi.org/10.1016/j.clml.2019.07.11610.1016/j.clml.2019.07.116 Search in Google Scholar

71. C. D. DiNardo, K. W. Pratz, A. Letai, B. A. Jonas, A. H. Wei, M. Thirman, M. Arellano, M. G. Frattini, H. Kantarjian, R. Popovic, B. Chyla, T. Xu, M. Dunbar, S. K. Agarwal, R. Humerickhouse, M. Mabry, J. Potluri, M. Konopleva and D. A. Pollyea, Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study, Lancet Oncol. 19 (2018) 216–228; https://doi.org/10.1016/S1470-2045(18)30010-X10.1016/S1470-2045(18)30010-X Search in Google Scholar

72. A. Wolska-Washer and T. Robak, Glasdegib in the treatment of acute myeloid leukemia, Future Oncol. Lond. Engl. 15 (2019) 3219–3232; https://doi.org/10.2217/fon-2019-017110.2217/fon-2019-017131432695 Search in Google Scholar

73. M. Heuser, T. Robak, P. Montesinos, B. Leber, W. M. Fiedler, D. A. Pollyea, A. Brown, A. O’Connell, W. Ma, G. Chan and J. E. Cortes, Glasdegib (GLAS) plus low-dose cytarabine (LDAC) in AML or MDS: BRIGHT AML 1003 final report and four-year overall survival (OS) follow-up, J. Clin. Oncol. 38 (2020) 7509–7509; https://doi.org/10.1200/JCO.2020.38.15_suppl.750910.1200/JCO.2020.38.15_suppl.7509 Search in Google Scholar

74. J. E. Cortes, F. H. Heidel, W. Fiedler, B. D. Smith, T. Robak, P. Montesinos, A. Candoni, B. Leber, M. A. Sekeres, D. A. Pollyea, R. Ferdinand, W. W. Ma, T. O’Brien, A. O’Connell, G. Chan and M. Heuser, Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy, J. Hematol. Oncol. 13 (2020) 92; https://doi.org/10.1186/s13045-020-00929-810.1186/s13045-020-00929-8736256332664995 Search in Google Scholar

75. E. S. Wang, M. Heuser, M. A. Sekeres, C. Papayannidis, A. Candoni, A. Merchant, A. Brown, A. O’Connell, W. Ma, G. Chan and J. E. Cortes, Effect of early blood counts on overall survival (OS) following glasdegib + LDAC in newly diagnosed AML: BRIGHT AML 1003 post hoc analysis, J. Clin. Oncol. 38 (2020) 7525–7525; https://doi.org/10.1200/JCO.2020.38.15_suppl.752510.1200/JCO.2020.38.15_suppl.7525 Search in Google Scholar

76. G. Tremblay, T. Westley, J. C. Cappelleri, B. Arondekar, G. Chan, T. J. Bell and A. Briggs, Overall survival of glasdegib in combination with low-dose cytarabine, azacitidine, and decitabine among adult patients with previously untreated AML: comparative effectiveness using simulated treatment comparisons, Clin. Outcomes Res. CEOR 11 (2019) 551–565; https://doi.org/10.2147/CEOR.S20348210.2147/CEOR.S203482673565331564931 Search in Google Scholar

77. S. van Beekhuizen, Y. Hu, A. Gezin, B. Heeg, T. Bell, M. Charaan, A. Brown, G. Chan and J. C. Cappelleri, The comparative effectiveness of glasdegib in combination with low-dose cytarabine versus azacitidine by bone marrow blasts counts among patients with newly-diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy, J. Clin. Oncol. 38 (2020) e19512–e19512; https://doi.org/10.1200/JCO.2020.38.15_suppl.e1951210.1200/JCO.2020.38.15_suppl.e19512 Search in Google Scholar

78. J. E. Lancet, R. S. Komrokji, K. L. Sweet, V. H. Duong, K. L. McGraw, L. Zhang, L. A. Nardelli, Z. Ma, R. R. Reich, E. Padron and A. F. List, Phase 2 trial of Smoothened (SMO) inhibitor PF-04449913 (PF-04) in refractory myelodysplastic syndromes (MDS), Blood 128 (2016) 3174–3174; https://doi.org/10.1182/blood.V128.22.3174.317410.1182/blood.V128.22.3174.3174 Search in Google Scholar

79. D. A. Sallman, R. S. Komrokji, K. L. Sweet, Q. Mo, K. L. McGraw, V. H. Duong, L. Zhang, L. A. Nardelli, E. Padron, A. F. List and J. E. Lancet, A phase 2 trial of the oral smoothened inhibitor glasdegib in refractory myelodysplastic syndromes (MDS), Leuk. Res. 81 (2019) 56–61; https://doi.org/10.1016/j.leukres.2019.03.00810.1016/j.leukres.2019.03.008778734931030089 Search in Google Scholar

80. A. M. Zeidan, M. W. Schuster, J. Krauter, J. A. Maertens, E. Gyan, M. Joris, T. F. Menne, P. Vyas, W. W. Ma, A. O’Connell, M. Zeremski, A. Kudla, G. Chan and M. A. Sekeres, Clinical benefit of glasdegib in combination with azacitidine or low-dose cytarabine in patients with acute myeloid leukemia, Blood 134 (2019) 3916–3916; https://doi.org/10.1182/blood-2019-12403410.1182/blood-2019-124034 Search in Google Scholar

81. A. Kent, S. Vasu, D. Schatz, N. Monson, S. Devine, C. Smith, J. A. Gutman and D. A. Pollyea, Glasdegib as maintenance therapy for patients with AML and MDS patients at high risk for postal-logeneic stem cell transplant relapse, Blood Adv. 4 (2020) 3102–3108; https://doi.org/10.1182/bloodadvances.202000199110.1182/bloodadvances.2020001991736234832634235 Search in Google Scholar

82. J. E. Cortes, H. Dombret, A. A. Merchant, T. Tauchi, C. DiRienzo, M. Zeremski, B. Sleight, X. Zhang, M. N. Shaik, T. Bell, G. Chan and M. A. Sekeres, Phase 3, randomized, placebo-controlled trials evaluating glasdegib in combination with intensive or nonintensive chemotherapy in patients with untreated acute myeloid leukemia, J. Clin. Oncol. 36 (2018) TPS7073–TPS7073; https://doi.org/10.1200/JCO.2018.36.15_suppl.TPS707310.1200/JCO.2018.36.15_suppl.TPS7073 Search in Google Scholar

83. J. E. Cortes, H. Dombret, A. Merchant, T. Tauchi, C. G. DiRienzo, B. Sleight, X. Zhang, E. P. Leip, N. Shaik, T. Bell, G. Chan and M. A. Sekeres, Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials, Future Oncol. 15 (2019) 3531–3545; https://doi.org/10.2217/fon-2019-037310.2217/fon-2019-037331516032 Search in Google Scholar

84. S. Lin, M. Shaik and A. Ruiz, Population pharmacokinetics of glasdegib in patients with advanced hematologic and solid tumors (in “American Society for Clinical Pharmacology and Therapeutics - Abstracts of 2018 Annual Meeting”), Clin. Pharmacol. Ther. 103 (Suppl 1) (2018) S78; https://doi.org/10.1002/cpt.99310.1002/cpt.993 Search in Google Scholar

85. S. Lin, N. Shaik, G. Martinelli, A. J. Wagner, J. Cortes and A. Ruiz-Garcia, Population pharmacokinetics of glasdegib in patients with advanced hematologic malignancies and solid tumors, J. Clin. Pharmacol. (2019); https://doi.org/10.1002/jcph.155610.1002/jcph.1556718737231769065 Search in Google Scholar

86. N. Shaik, B. Hee, Y. Liang and R. R. LaBadie, Absolute oral bioavailability of glasdegib (PF-04449913), a Smoothened inhibitor, in randomized healthy volunteers, Clin. Pharmacol. Drug Dev. 8 (2019) 895–902; https://doi.org/10.1002/cpdd.69210.1002/cpdd.692685040330977980 Search in Google Scholar

87. N. Giri, L. H. Lam, R. R. LaBadie, J. F. Krzyzaniak, H. Jiang, B. Hee, Y. Liang and M. N. Shaik, Evaluation of the effect of new formulation, food, or a proton pump inhibitor on the relative bio-availability of the Smoothened inhibitor glasdegib (PF-04449913) in healthy volunteers, Cancer Chemother. Pharmacol. 80 (2017) 1249–1260; https://doi.org/10.1007/s00280-017-3472-910.1007/s00280-017-3472-929086063 Search in Google Scholar

88. N. Shaik, B. Hee, H. Wei and R. R. LaBadie, Evaluation of the effects of formulation, food, or a proton-pump inhibitor on the pharmacokinetics of glasdegib (PF-04449913) in healthy volunteers: a randomized phase I study, Cancer Chemother. Pharmacol. 83 (2019) 463–472; https://doi.org/10.1007/s00280-018-3748-810.1007/s00280-018-3748-8639447430536154 Search in Google Scholar

89. J. L. Lam, A. Vaz, B. Hee, Y. Liang, X. Yang and M. N. Shaik, Metabolism, excretion and pharmacokinetics of [14C]glasdegib (PF-04449913) in healthy volunteers following oral administration, Xenobiotica Fate Foreign Compd. Biol. Syst. 47 (2017) 1064–1076; https://doi.org/10.1080/00498254.2016.126130710.1080/00498254.2016.126130727866461 Search in Google Scholar

90. M. N. Shaik, R. R. LaBadie, D. Rudin and W. J. Levin, Evaluation of the effect of food and ketoconazole on the pharmacokinetics of the Smoothened inhibitor PF-04449913 in healthy volunteers, Cancer Chemother. Pharmacol. 74 (2014) 411–418; https://doi.org/10.1007/s00280-014-2502-010.1007/s00280-014-2502-024944041 Search in Google Scholar

91. European Medicines Agency, Glasdegib (DAURISMO): EPAR - Product Information, https://www.ema.europa.eu/en/documents/product-information/daurismo-epar-product-information_en.pdf (accessed 10 October 2020). Search in Google Scholar

92. M. N. Shaik, B. Hee, H. Wei and R. R. LaBadie, Evaluation of the effect of rifampin on the pharmacokinetics of the Smoothened inhibitor glasdegib in healthy volunteers, Br. J. Clin. Pharmacol. 84 (2018) 1346–1353; https://doi.org/10.1111/bcp.1356810.1111/bcp.13568598054129488303 Search in Google Scholar

93. A. Ruiz-Garcia, N. Shaik, S. Lin, C. Jamieson, M. Heuser and G. Chan, Evaluation of the relationship of glasdegib exposure and safety end points in patients with refractory solid tumors and hematologic malignancies, J. Clin. Pharmacol. (2020) jcph.1742; https://doi.org/10.1002/jcph.174210.1002/jcph.1742789144132974950 Search in Google Scholar

94. M. Tavares, S. Chacim and J. M. Mariz, Compassionate use of glasdegib in combination with low-dose cytarabine for relapsed, refractory acute myeloid leukemia or high-risk myelodysplastic syndrome, Ann. Hematol. (2020); https://doi.org/10.1007/s00277-020-04291-010.1007/s00277-020-04291-033001280 Search in Google Scholar

95. N. Shaik, L. Mendes da Costa, B. Hee, Y. Liang and R. R. LaBadie, A thorough QT study to evaluate the effect of glasdegib on cardiac repolarization in healthy adult subjects (in “Abstracts for the Ninth American Conference on Pharmacometrics (ACoP9)”), J. Pharmacokinet. Pharmacodyn. 45 (2018) S87 [Abstract no. T-092]; https://doi.org/10.1007/s10928-018-9606-910.1007/s10928-018-9606-930203256 Search in Google Scholar

96. J. C. Masters, N. Shaik, L. Mendes da Costa, B. Hee and R. R. LaBadie, Clinical and model-based evaluation of the effect of glasdegib on cardiac repolarization from a randomized thorough QT study, Clin. Pharmacol. Drug Dev. (2020) cpdd.862; https://doi.org/10.1002/cpdd.86210.1002/cpdd.862798388832790066 Search in Google Scholar

97. N. Sarapa and M. R. Britto, Challenges of characterizing proarrhythmic risk due to QTc prolongation induced by nonadjuvant anticancer agents, Expert Opin. Drug Saf. 7 (2008) 305–318; https://doi.org/10.1517/14740338.7.3.30510.1517/14740338.7.3.30518462188 Search in Google Scholar

98. E. Park, J. Willard, D. Bi, M. Fiszman, D. Kozeli and J. Koerner, The impact of drug-related QT prolongation on FDA regulatory decisions, Int. J. Cardiol. 168 (2013) 4975–4976; https://doi.org/10.1016/j.ijcard.2013.07.13610.1016/j.ijcard.2013.07.13623920061 Search in Google Scholar

99. R. J. Lipinski, P. R. Hutson, P. W. Hannam, R. J. Nydza, I. M. Washington, R. W. Moore, G. G. Girdaukas, R. E. Peterson and W. Bushman, Dose- and route-dependent teratogenicity, toxicity, and pharmacokinetic profiles of the hedgehog signaling antagonist cyclopamine in the mouse, Toxicol. Sci. 104 (2008) 189–197; https://doi.org/10.1093/toxsci/kfn07610.1093/toxsci/kfn076292786818411234 Search in Google Scholar

100. E. Morinello, M. Pignatello, L. Villabruna, P. Goelzer and H. Bürgin, Embryofetal development study of vismodegib, a Hedgehog pathway inhibitor, in rats, Birth Defects Res. B. Dev. Reprod. Toxicol. 101 (2014) 135–143; https://doi.org/10.1002/bdrb.2109310.1002/bdrb.2109324692404 Search in Google Scholar

101. Glasdegib, Drugs Lact. Database Lact. Bethesda (MD): National Library of Medicine (US); Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK535600/ Search in Google Scholar

102. S. V. Mohan and A. L. S. Chang, Management of cutaneous and extracutaneous side effects of smoothened inhibitor therapy for advanced basal cell carcinoma, Clin. Cancer Res. 21 (2015) 2677–2683; https://doi.org/10.1158/1078-0432.CCR-14-318010.1158/1078-0432.CCR-14-318025792568 Search in Google Scholar

103. M. E. Lacouture, B. Dréno, P. A. Ascierto, R. Dummer, N. Basset-Seguin, K. Fife, S. Ernst, L. Licitra, R. I. Neves, K. Peris, S. Puig, J. Sokolof, A. Sekulic, A. Hauschild and R. Kunstfeld, Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma, The Oncologist 21 (2016) 1218–1229; https://doi.org/10.1634/theoncologist.2016-018610.1634/theoncologist.2016-0186506153227511905 Search in Google Scholar

104. A. A. Jacobsen, A. R. Kydd and J. Strasswimmer, Practical management of the adverse effects of Hedgehog pathway inhibitor therapy for basal cell carcinoma, J. Am. Acad. Dermatol. 76 (2017) 767–768; https://doi.org/10.1016/j.jaad.2016.04.06310.1016/j.jaad.2016.04.06328325399 Search in Google Scholar

105. X. Song, Y. Peng, X. Wang, Y. Chen, L. Jin, T. Yang, M. Qian, W. Ni, X. Tong and J. Lan, Incidence, survival, and risk factors for adults with acute myeloid leukemia not otherwise specified and acute myeloid leukemia with recurrent genetic abnormalities: analysis of the surveillance, epidemiology, and end results (SEER) database, 2001–2013, Acta Haematol. 139 (2018) 115–127; https://doi.org/10.1159/00048622810.1159/00048622829455198 Search in Google Scholar

106. German-Austrian AML Study Group (AMLSG), G. Nagel, D. Weber, E. Fromm, S. Erhardt, M. Lübbert, W. Fiedler, T. Kindler, J. Krauter, P. Brossart, A. Kündgen, H. R. Salih, J. Westermann, G. Wulf, B. Hertenstein, M. Wattad, K. Götze, D. Kraemer, T. Heinicke, M. Girschikofsky, H. G. Derigs, H. A. Horst, C. Rudolph, M. Heuser, G. Göhring, V. Teleanu, L. Bullinger, F. Thol, V. I. Gaidzik, P. Paschka, K. Döhner, A. Ganser, H. Döhner, R. F. Schlenk and the German-Austrian AML Study Group (AMLSG), Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO), Ann. Hematol. 96 (2017) 1993–2003; https://doi.org/10.1007/s00277-017-3150-310.1007/s00277-017-3150-3569109129090343 Search in Google Scholar

107. X. Thomas and M. Heiblig, An evaluation of glasdegib for the treatment of acute myelogenous leukemia, Expert Opin. Pharmacother. 21 (2020) 523–530; https://doi.org/10.1080/14656566.2020.171309410.1080/14656566.2020.171309432027196 Search in Google Scholar

108. N. Daver, A. H. Wei, D. A. Pollyea, A. T. Fathi, P. Vyas and C. D. DiNardo, New directions for emerging therapies in acute myeloid leukemia: the next chapter, Blood Cancer J. 10 (2020) 107; https://doi.org/10.1038/s41408-020-00376-110.1038/s41408-020-00376-1759922533127875 Search in Google Scholar

109. J. E. Cortes, A. Candoni, R. E. Clark, B. Leber, P. Montesinos, P. Vyas, A. M. Zeidan and M. Heuser, Selection and management of older patients with acute myeloid leukemia treated with glasdegib plus low-dose cytarabine: expert panel review, Leuk. Lymphoma (2020) 1–19; https://doi.org/10.1080/10428194.2020.181744510.1080/10428194.2020.181744532967493 Search in Google Scholar

110. J. C. Masters, R. R. LaBadie, J. Salageanu, J. Li and N. Shail, Pharmacokinetics and safety of glasdegib in participants with moderate/severe hepatic impairment: a phase I, single-dose, matched case-control study, Clin. Pharmacol. Drug Dev. (2020); https://doi.org/10.1002/cpdd.897.10.1002/cpdd.897835930833356019 Search in Google Scholar

111. N. Shaik, R. LaBadie, B. Hee and G. Chan, Evaluation of the impact of renal impairment on the pharmacokinetics of glasdegib, Clin. Pharmacol. Ther. 107 (2020) (S1) S69–S69 [Abstract no. PII-126]; https://doi.org/10.1002/cpt.173210.1002/cpt.173232060909 Search in Google Scholar

112. H. A. Pham, S. Milev, S. Li, D. Zou, Y. Hu, B. Heeg and T. J. Bell, Budget impact of glasdegib in combination with low-dose cytarabine for the treatment of first-line acute myeloid leukemia in the United States, Blood 134 (2019) 5852–5852; https://doi.org/10.1182/blood-2019-12270910.1182/blood-2019-122709 Search in Google Scholar

113. S. R. Goldsmith, A. R. Lovell and M. A. Schroeder, Glasdegib for the treatment of adult patients with newly diagnosed acute myeloid leukemia or high-grade myelodysplastic syndrome who are elderly or otherwise unfit for standard induction chemotherapy, Drugs Today 55 (2019) 545; https://doi.org/10.1358/dot.2019.55.9.302016010.1358/dot.2019.55.9.302016031584572 Search in Google Scholar

114. R. M. Shallis, N. A. Podoltsev, T. Prebet and A. M. Zeidan, Trial in progress: Glad-AML – a randomized, phase 2 trial of glasdegib with two standard decitabine regimens for older patients with newly-diagnosed, poor-risk acute myeloid leukemia, Blood 136 (2020) 29–29; https://doi.org/10.1182/blood-2020-13942810.1182/blood-2020-139428 Search in Google Scholar

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