Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify onco...Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto展开更多
The cure rate of childhood acute lymphoblastic leukemia(ALL)has exceeded 90%in some contemporary clinical trials.However,the dose intensity of conventional chemotherapy has been pushed to its limit.Further improvement...The cure rate of childhood acute lymphoblastic leukemia(ALL)has exceeded 90%in some contemporary clinical trials.However,the dose intensity of conventional chemotherapy has been pushed to its limit.Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno-and cellular-therapy approaches together with precise risk stratification.Children with ETV6-RUNX1 or hyperdiploid>50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment.Patients with Philadelphia chromosome(Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib.BH3 profiling and other preclinical methods have identified several high-risk subtypes,such as hypodiplod,early T-cell precursor,immature T-cell,KMT2A-rearranged,Ph-positive and TCF-HLF-positive ALL,that may respond to BCL-2 inhibitor venetoclax.There are other fusions or mutations that may serve as putative targets,but effective targeted therapy has yet to be established.For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions,current approaches that offer hope include blinatumomab,inotuzumab and CAR-T cell therapy for B-ALL,and daratumumab and nelarabine for T-ALL.With the expanding therapeutic armamentarium,we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.展开更多
文摘Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto
基金This work is supported in part by the US National Institute of Health(Nos.P30CA021765,P50GM115279,and R01CA036401)American Lebanese Syrian Associated Charities(ALSAC).
文摘The cure rate of childhood acute lymphoblastic leukemia(ALL)has exceeded 90%in some contemporary clinical trials.However,the dose intensity of conventional chemotherapy has been pushed to its limit.Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno-and cellular-therapy approaches together with precise risk stratification.Children with ETV6-RUNX1 or hyperdiploid>50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment.Patients with Philadelphia chromosome(Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib.BH3 profiling and other preclinical methods have identified several high-risk subtypes,such as hypodiplod,early T-cell precursor,immature T-cell,KMT2A-rearranged,Ph-positive and TCF-HLF-positive ALL,that may respond to BCL-2 inhibitor venetoclax.There are other fusions or mutations that may serve as putative targets,but effective targeted therapy has yet to be established.For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions,current approaches that offer hope include blinatumomab,inotuzumab and CAR-T cell therapy for B-ALL,and daratumumab and nelarabine for T-ALL.With the expanding therapeutic armamentarium,we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.
