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Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing
- Source :
- Oncotarget
- Publication Year :
- 2017
-
Abstract
- Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4; 14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.
- Subjects :
- 0301 basic medicine
Drug
LOW-DOSE DEXAMETHASONE
media_common.quotation_subject
medicine.medical_treatment
precision medicine
3122 Cancers
Pharmacology
drug sensitivity and resistance testing
SINGLE-AGENT
Targeted therapy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
TARGETED THERAPY
Refractory
Panobinostat
medicine
COMBINATION
Multiple myeloma
media_common
PANOBINOSTAT
business.industry
WORKING GROUP
Precision medicine
medicine.disease
3. Good health
GLUCOCORTICOID-RECEPTOR
multiple myeloma
functional screening
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
CELLS
PHASE-II
high-risk myeloma
3111 Biomedicine
business
RISK-STRATIFICATION
Progressive disease
Ex vivo
Research Paper
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....fae9b49c2b9b709ccb650583d1ff6e32