Review article

https://doi.org/10.2478/acph-2022-0007

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

CYRIL FERSING ; University of Montpellier, Montpellier Cancer Institute (ICM), Montpellier, France; Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université de Montpellier, ENSCM, UFR des Sciences Pharmaceutiques et Biologiques, Montpellier Cedex, France
FANNY MATHIAS ; Aix Marseille Univ, Pharmacy Department, Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Marseille, France; Aix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS30064, 13385, Marseille Cedex 05, France

Abstract

Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML). The significant shift toward the use of these novel therapeutics, administered either alone or in combination with intensive or low-intensity chemotherapy, changes the prospects for the control of this disease, especially for elderly patients. Glasdegib, an oral Hedgehog pathway inhibitor, showed satisfactory response rates associated with moderate toxicity and less early mortality than standard induction regimens in this population. It was approved in November 2018 by the FDA and in June 2020 by the EMA for use in combination with low-dose cytarabine as a treatment of newly-diagnosed AML in patients aged ≥ 75 and/or unfit for intensive induction chemotherapy. The current paper proposes an extensive, up-to-date review of the preclinical and clinical development of glasdegib. Elements of its routine clinical use and the landscape of ongoing clinical trials are also stated.

Keywords

glasdegib; PF-04449913; PF-913; acute myeloid leukemia; Hedgehog pathway; smoothened

Hrčak ID:

253976

URI

https://hrcak.srce.hr/253976

Publication date:

31.3.2022.

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