TY - JOUR
T1 - Novel agents for the treatment of childhood acute leukemia
AU - Annesley, Colleen E.
AU - Brown, Patrick
N1 - Funding Information:
This work was supported by St. Baldrick’s Foundation Fellowship Awards (C.E.A.), Leukemia and Lymphoma Society Scholar Award (P.B.), and American Cancer Society Research Scholar Grant (P.B.).
PY - 2015/4
Y1 - 2015/4
N2 - Together, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) make up approximately one-third of all pediatric cancer diagnoses. Despite remarkable improvement in the treatment outcomes of these diseases over the past several decades, the prognosis for certain high-risk groups of leukemia and for relapsed disease remains poor. However, recent insights into different types of driver' lesions of leukemogenesis, such as the aberrant activation of signaling pathways and various epigenetic modifications, have led to the discovery of novel agents that specifically target the mechanism of transformation. In parallel, emerging approaches in cancer immunotherapy have led to newer therapies that can exploit and harness cytotoxic immunity directed against malignant cells. This review details the rationale and implementation of recent and specifically targeted therapies in acute pediatric leukemia. Topics covered include the inhibition of critical cell signaling pathways [BCR-ABL, FMS-like tyrosine kinase 3 (FLT3), mammalian target of rapamycin (mTOR), and Janus-associated kinase (JAK)], proteasome inhibition, inhibition of epigenetic regulators of gene expression [DNA methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, and disruptor of telomeric signaling-1 (DOT1L) inhibitors], monoclonal antibodies and immunoconjugated toxins, bispecific T-cell engaging (BiTE) antibodies, and chimeric antigen receptor-modified (CAR) T cells.
AB - Together, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) make up approximately one-third of all pediatric cancer diagnoses. Despite remarkable improvement in the treatment outcomes of these diseases over the past several decades, the prognosis for certain high-risk groups of leukemia and for relapsed disease remains poor. However, recent insights into different types of driver' lesions of leukemogenesis, such as the aberrant activation of signaling pathways and various epigenetic modifications, have led to the discovery of novel agents that specifically target the mechanism of transformation. In parallel, emerging approaches in cancer immunotherapy have led to newer therapies that can exploit and harness cytotoxic immunity directed against malignant cells. This review details the rationale and implementation of recent and specifically targeted therapies in acute pediatric leukemia. Topics covered include the inhibition of critical cell signaling pathways [BCR-ABL, FMS-like tyrosine kinase 3 (FLT3), mammalian target of rapamycin (mTOR), and Janus-associated kinase (JAK)], proteasome inhibition, inhibition of epigenetic regulators of gene expression [DNA methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, and disruptor of telomeric signaling-1 (DOT1L) inhibitors], monoclonal antibodies and immunoconjugated toxins, bispecific T-cell engaging (BiTE) antibodies, and chimeric antigen receptor-modified (CAR) T cells.
KW - ALL
KW - AML
KW - CAR T-cells
KW - EPZ-5676
KW - FLT3
KW - blinatumomab
KW - carfilzomib
KW - moxetumomab
UR - http://www.scopus.com/inward/record.url?scp=84993813859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84993813859&partnerID=8YFLogxK
U2 - 10.1177/2040620714565963
DO - 10.1177/2040620714565963
M3 - Review article
C2 - 25830014
AN - SCOPUS:84993813859
SN - 2040-6207
VL - 6
SP - 61
EP - 79
JO - Therapeutic Advances in Hematology
JF - Therapeutic Advances in Hematology
IS - 2
ER -