2020
DOI: 10.3390/jcm9092934
|View full text |Cite
|
Sign up to set email alerts
|

Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence

Abstract: Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy characterized by excessive proliferation and accumulation of immature myeloid blasts in the bone marrow. AML has a very poor 5-year survival rate of just 16% in the UK; hence, more efficacious, tolerable, and targeted therapy is required. Persistent leukemia stem cell (LSC) populations underlie patient relapse and development of resistance to therapy. Identification of critical oncogenic signaling pathways in AML LSC may provide ne… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

2
34
0

Year Published

2021
2021
2023
2023

Publication Types

Select...
10

Relationship

1
9

Authors

Journals

citations
Cited by 60 publications
(36 citation statements)
references
References 321 publications
2
34
0
Order By: Relevance
“…In addition, PIM kinases are critical downstream of ABL (Abelson) and FLT3 (FMS-related tyrosine kinase 3) oncogenes and are required in driving tumorigenesis. Constitutively active FLT3 signaling up-regulates PIM1 expression and PIM is a key contributor to FLT3-induced proliferative and anti-apoptotic pathways [ 9 ]. BCR-ABL plays an important role in mediated cell transformation through induced PIM1 expression via active STAT5.…”
Section: Background—expression and Regulation Of Pim Kinasesmentioning
confidence: 99%
“…In addition, PIM kinases are critical downstream of ABL (Abelson) and FLT3 (FMS-related tyrosine kinase 3) oncogenes and are required in driving tumorigenesis. Constitutively active FLT3 signaling up-regulates PIM1 expression and PIM is a key contributor to FLT3-induced proliferative and anti-apoptotic pathways [ 9 ]. BCR-ABL plays an important role in mediated cell transformation through induced PIM1 expression via active STAT5.…”
Section: Background—expression and Regulation Of Pim Kinasesmentioning
confidence: 99%
“…The discrepancy between our results and the above studies may be explained by recent findings showing how cancer cells react to a signalling blockade. In fact, this highly active pro-survival pathway is sustained by considerable positive feedback [ 39 ], as also demonstrated by the failure of PI3K/Akt inhibitors as monotherapy in most clinical trials [ 40 , 41 ]. Thus, cancer cells adapt very rapidly to PI3K inhibition, mainly due to feedback signals leading to activation or enhanced expression of growth factor receptors, such as IR/IRS1/IGF-1R, which, in turn, reactivate PI3K [ 42 , 43 ].…”
Section: Discussionmentioning
confidence: 99%
“…The uncontrolled activation of the PI3K/AKT/mTOR pathway, which is closely associated with several types of cancer, is involved in tumorigenesis, proliferation, invasion, cell cycle progression, apoptosis, metastasis and chemotherapy resistance (2,24,25). Recent studies have shown that the PI3K/AKT/mTOR pathway is also associated with angiogenesis, cytoskeleton, inflammatory response and oxidative stress (26)(27)(28).…”
Section: Introductionmentioning
confidence: 99%