Rational combination therapies targeting survival signaling in aggressive B-cell leukemia/lymphoma.
Curr Opin Hematol
; 21(4): 297-308, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24811162
ABSTRACT
PURPOSE OF REVIEW The identification of oncogenic 'driver' mutations and activated survival pathways in selected aggressive B-cell malignancies directs the development of novel adjunctive therapies using targeted small molecule inhibitors. With a focus on diffuse large B-cell lymphoma 'not otherwise specified', Hodgkin lymphoma and childhood B-cell precursor acute lymphoblastic leukemia, this review will provide an up-to-date account of the current literature on the development of new molecularly targeted treatment modalities for aggressive B-cell malignancies. RECENT FINDINGS:
Subclassification of B-cell malignancies depending on their particular genetic 'driver' lesions and transcriptional and/or signaling signatures has led to the development of targeted therapeutic approaches using small molecule inhibitors to amend current combination chemotherapy.SUMMARY:
Treatment outcome with current combination chemotherapy is still poor for subsets of aggressive B-cell malignancies, and demands development of targeted therapeutic approaches. Advanced gene expression profiling and genomic sequencing have revealed a more detailed landscape of recurrent alterations, allowing a better subclassification of B-cell lymphomas and leukemias. Many alterations directly or indirectly lead to activation of survival signaling pathways and expression of key oncoproteins and prosurvival molecules, including Janus kinase-signal transducer and activator of transcription (JAK-STAT), phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), avian myelocytomatosis viral oncogene homolog (MYC) and B-cell lymphoma 2 (BCLl-2). Small molecule inhibitors targeting these proteins and pathways are currently being tested in clinical trials and preclinically to improve chemotherapeutic regimes and treatment outcomes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia de Células B
/
Transducción de Señal
/
Regulación Neoplásica de la Expresión Génica
/
Linfoma de Células B
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Opin Hematol
Asunto de la revista:
HEMATOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Australia