Drug repurposing for targeting cyclic nucleotide transporters in acute leukemias - A missed opportunity.
3',5'-cyclic adenosine monophosphate (cAMP)
ATP-binding cassette (ABC) transporters
Acute lymphoblastic leukemia (ALL)
Acute myelogenous leukemia (AML)
Efflux
Inhibitors of cAMP efflux (ICE)
Journal
Seminars in cancer biology
ISSN: 1096-3650
Titre abrégé: Semin Cancer Biol
Pays: England
ID NLM: 9010218
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
25
07
2019
revised:
01
10
2019
accepted:
03
02
2020
pubmed:
12
2
2020
medline:
1
3
2022
entrez:
12
2
2020
Statut:
ppublish
Résumé
While current treatment regimens for acute leukemia can dramatically improve patient survival, there remains room for improvement. Due to its roles in cell differentiation, cell survival, and apoptotic signaling, modulation of the cyclic AMP (cAMP) pathway has provided a meaningful target in hematological malignancies. Several studies have demonstrated that gene expression profiles associated with increased pro-survival cAMP activity or downregulation of various pro-apoptotic factors associated with the cAMP pathway are apparent in acute leukemia patients. Previous work to increase leukemia cell intracellular cAMP focused on the use of cAMP analogs, stimulating cAMP production via transmembrane-associated adenylyl cyclases, or decreasing cAMP degradation by inhibiting phosphodiesterase activity. However, targeting cyclic nucleotide efflux by ATP-binding cassette (ABC) transporters represents an unexplored approach for modulation of intracellular cyclic nucleotide levels. Preliminary studies have shown that inhibition of cAMP efflux can stimulate leukemia cell differentiation, cell growth arrest, and apoptosis, indicating that targeting cAMP efflux may show promise for future therapeutic development. Furthermore, inhibition of cyclic nucleotide transporter activity may also contribute multiple anticancer benefits by reducing extracellular pro-survival signaling in malignant cells. Hence, several opportunities for drug repurposing may exist for targeting cyclic nucleotide transporters.
Identifiants
pubmed: 32044470
pii: S1044-579X(20)30037-7
doi: 10.1016/j.semcancer.2020.02.004
pmc: PMC7415530
mid: NIHMS1563606
pii:
doi:
Substances chimiques
ATP-Binding Cassette Transporters
0
Antineoplastic Agents
0
Cyclic AMP
E0399OZS9N
Cyclic GMP
H2D2X058MU
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
199-208Subventions
Organisme : NCI NIH HHS
ID : P30 CA118100
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237165
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001449
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121176
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007736
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
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