Back to Search
Start Over
Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma
- Source :
- British Journal of Haematology. 177:557-561
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA-dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL.
- Subjects :
- 0301 basic medicine
Dual targeting
Apoptosis
Pyridinium Compounds
Lymphoma, Mantle-Cell
Mice, SCID
Cyclic N-Oxides
Lactones
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
hemic and lymphatic diseases
medicine
Animals
Humans
MCL1
Enzyme Inhibitors
Dinaciclib
Orlistat
biology
Indolizines
Hematology
Bridged Bicyclo Compounds, Heterocyclic
medicine.disease
Cyclin-Dependent Kinases
Cell biology
Fatty acid synthase
030104 developmental biology
Cell Death Induction
Proto-Oncogene Proteins c-bcl-2
chemistry
030220 oncology & carcinogenesis
biology.protein
Myeloid Cell Leukemia Sequence 1 Protein
Female
Mantle cell lymphoma
CDK inhibitor
Subjects
Details
- ISSN :
- 00071048
- Volume :
- 177
- Database :
- OpenAIRE
- Journal :
- British Journal of Haematology
- Accession number :
- edsair.doi.dedup.....7b46baa76c5d3fe5e0613fcb79529e7c