Opinion statement
Acute myeloid leukemia (AML) disease prognosis is poor and there is a high risk of chemo-resistant relapse for both young and old patients. Thus, there is a demand for alternative and target-specific drugs to improve the 5-year survival rate. Current treatment mainstays include chemotherapy, or mutation-specific targeting molecules including FLT3 inhibitors, IDH inhibitors, and monoclonal antibodies. Efforts to devise new, targeted therapy have included recent advances in methods for high-throughput genomic screening and the availability of computer-assisted techniques for the design of novel agents predicted to specifically inhibit mutant molecules involved in leukemogenesis. Crosstalk between the leukemia cells and the bone marrow microenvironment through cell surface molecules, such as the integrins αvβ3 and αvβ5, might influence drug response and AML progression. This review article focuses on current AML treatment options, new AML targeted therapies, the role of integrins in AML progression, and a potential therapeutic agent—integrin αvβ3 antagonist.
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Abbreviations
- AML:
-
Acute myeloid leukemia
- BCL-2:
-
B-cell lymphoma gene 2
- CAM:
-
Chick egg chorioallantoic membrane
- CDK:
-
Cyclin-dependent kinase
- c-KIT:
-
C-kit is a type of receptor tyrosine kinase, also called CD117
- c-FMS:
-
Proto-oncogene that codes for the MCSF (CSF1) receptor
- EGF:
-
Epidermal growth factor
- EGFR:
-
EGF receptor
- EMT:
-
Epithelial–mesenchymal transition
- FAK:
-
Focal adhesion kinase
- FGF:
-
Basic fibroblast growth factor
- FLT3:
-
FMS-like tyrosine kinase 3
- IDH:
-
Isocitrate dehydrogenase
- JAK-2:
-
Janus kinase-2
- LSD:
-
Lysine-specific demethylase
- MAPK:
-
Mitogen-activated protein kinase
- MDM2:
-
Mouse double minute chromosome 2
- miR:
-
MicroRNAs
- NDAT:
-
Nano-diamino-tetrac
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NPM:
-
Nucleophosmin
- P-bi-TAT:
-
Polyethylene glycol (PEG) covalently bonded with two bi-tri-azole tetraiodothyroacetic acid molecules
- PD-1:
-
Programmed cell death protein 1
- PD-L1:
-
Programmed death-ligand 1
- PDGF:
-
Platelet-derived growth factor
- PEG:
-
Polyethylene glycol
- PI3K:
-
Phosphatidylinositol 3-kinase
- STAT:
-
Signal transducer and activator of transcription
- Tetrac:
-
Tetraiodothyroacetic acid
- TGFβ:
-
Transforming growth factor β
- TK:
-
Tyrosine kinase
- T4:
-
l-Thyroxine
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Shaheedul A. Sami declares that he has no conflict of interest.
Noureldien H. E. Darwish declares that he has no conflict of interest.
Amanda N. M. Barile declares that she has no conflict of interest.
Shaker A. Mousa was issued a patent that is owned by NanoPharmaceuticals LLC, and he owns stock in NanoPharmaceuticals LLC, which is developing anticancer drugs.
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Sami, S.A., Darwish, N.H.E., Barile, A.N.M. et al. Current and Future Molecular Targets for Acute Myeloid Leukemia Therapy. Curr. Treat. Options in Oncol. 21, 3 (2020). https://doi.org/10.1007/s11864-019-0694-6
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DOI: https://doi.org/10.1007/s11864-019-0694-6