Literature DB >> 28799432

Targeted therapies in Acute Myeloid Leukemia: a focus on FLT-3 inhibitors and ABT199.

Kiran Naqvi1, Marina Konopleva1, Farhad Ravandi1.   

Abstract

INTRODUCTION: Acute myeloid leukemia (AML) remains a therapeutic challenge. Despite ongoing research, the standard therapy for AML has not changed significantly in the past four decades. With the identification of cytogenetic and molecular abnormalities, several promising therapeutic agents are currently being investigated. FLT3 mutation is a well-recognized target seen in 30% of the cytogenetically normal AML. More recently, the BCL2 family of anti-apoptotic proteins have also generated great interest as a therapeutic target. Areas covered: This review will cover the role of FLT3 inhibitors in AML, discussing trials in relapsed/refractory AML and in the frontline setting, including the young and elderly patient population. Toxicities and potential mechanism of resistance will also be covered. In addition, most current studies demonstrating the role of BCL-2 inhibitors namely ABT-199/venetoclax in AML will also be discussed. Expert commentary: AML is one of the most heterogeneous group of hematological malignancies. It remains a therapeutic challenge with limited therapeutic progress despite ongoing research. With the identification of different mutations in AML, several drugs are being evaluated in clinical trials. Targeted agents such as FLT3 inhibitors and BH3 mimetics so far have shown promising results in terms of response and toxicity profile.

Entities:  

Keywords:  ABT-199; Acute myeloid leukemia; BCL2 inhibitors; FLT3 inhibitors; myeloid malignancies

Mesh:

Substances:

Year:  2017        PMID: 28799432     DOI: 10.1080/17474086.2017.1366852

Source DB:  PubMed          Journal:  Expert Rev Hematol        ISSN: 1747-4094            Impact factor:   2.929


  7 in total

1.  The irreversible ERBB1/2/4 inhibitor neratinib interacts with the BCL-2 inhibitor venetoclax to kill mammary cancer cells.

Authors:  Laurence Booth; Jane L Roberts; Francesca Avogadri-Connors; Richard E Cutler; Alshad S Lalani; Andrew Poklepovic; Paul Dent
Journal:  Cancer Biol Ther       Date:  2018-01-22       Impact factor: 4.742

2.  Panobinostat and venetoclax enhance the cytotoxicity of gemcitabine, busulfan, and melphalan in multiple myeloma cells.

Authors:  Benigno C Valdez; Yang Li; David Murray; Yan Liu; Yago Nieto; Qaiser Bashir; Muzaffar H Qazilbash; Borje S Andersson
Journal:  Exp Hematol       Date:  2020-01-15       Impact factor: 3.084

3.  Leukemia Stem Cells in the Pathogenesis, Progression, and Treatment of Acute Myeloid Leukemia.

Authors:  Kanak Joshi; Lei Zhang; Peter Breslin S J; Jiwang Zhang
Journal:  Adv Exp Med Biol       Date:  2019       Impact factor: 3.650

4.  Impact of elevated anti-apoptotic MCL-1 and BCL-2 on the development and treatment of MLL-AF9 AML in mice.

Authors:  Natasha S Anstee; Rebecca A Bilardi; Ashley P Ng; Zhen Xu; Mikara Robati; Cassandra J Vandenberg; Suzanne Cory
Journal:  Cell Death Differ       Date:  2018-11-23       Impact factor: 15.828

Review 5.  Targeting Oncogenic Signaling in Mutant FLT3 Acute Myeloid Leukemia: The Path to Least Resistance.

Authors:  Dilana Staudt; Heather C Murray; Tabitha McLachlan; Frank Alvaro; Anoop K Enjeti; Nicole M Verrills; Matthew D Dun
Journal:  Int J Mol Sci       Date:  2018-10-16       Impact factor: 5.923

6.  Venetoclax combines synergistically with FLT3 inhibition to effectively target leukemic cells in FLT3-ITD+ acute myeloid leukemia models.

Authors:  Raghuveer Singh Mali; Qi Zhang; Rosa Anna DeFilippis; Antonio Cavazos; Vinitha Mary Kuruvilla; Jayant Raman; Vidhi Mody; Edna F Choo; Monique Dail; Neil P Shah; Marina Konopleva; Deepak Sampath; Elisabeth A Lasater
Journal:  Haematologica       Date:  2021-04-01       Impact factor: 9.941

Review 7.  Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives.

Authors:  Álvaro Pinto-Merino; Jorge Labrador; Pablo Zubiaur; Raquel Alcaraz; María José Herrero; Pau Montesinos; Francisco Abad-Santos; Miriam Saiz-Rodríguez
Journal:  Pharmaceutics       Date:  2022-03-03       Impact factor: 6.321

  7 in total

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