Article ; Online: Hematological malignancies and molecular targeting therapy.
European journal of pharmacology
2019 Volume 862, Page(s) 172641
Abstract: Recent genetic analysis using next-generation sequencing (NGS) vastly improved the understanding of molecular mechanism of hematological malignancies. Many molecular targeting drugs have since been used in the clinic, which is timely as clinical outcomes ...
| Abstract | Recent genetic analysis using next-generation sequencing (NGS) vastly improved the understanding of molecular mechanism of hematological malignancies. Many molecular targeting drugs have since been used in the clinic, which is timely as clinical outcomes using conventional chemotherapy and hematopoietic stem cell transplantation (HSCT) reached a plateau. The first memorable success in this field was imatinib, a first-generation tyrosine kinase inhibitor (TKI), which has been applied in chronic myeloid leukemia (CML) since 2001. Imatinib drastically changed CML treatment and many CML patients no longer require HSCT. Recently, the second generation TKIs, dasatinib, nilotinib, and ponatinib, have also been available for CML patients. Acute lymphoblastic leukemia (ALL) is sub-categorized based on cytogenetic or molecular genetic abnormalities. Chemotherapy and HSCT combined with TKI improved the event-free survival rate from 20% to 80% in Philadelphia (Ph) chromosome-positive ALL. Reportedly, another Ph-like ALL subgroup with poor prognosis can also be treated by TKIs; additionally, cell therapies that include bispecific T-cell engagers or chimeric antigen receptor (CAR)-T therapy are emerging. Acute myeloid leukemia (AML) is a heterogenous disease and FMS-like related tyrosine kinase-3 (FLT3)-internal tandem duplication, is the most robust marker for poor prognosis. Several first-generation TKIs have been studied for clinical use. Notably, chemotherapy plus midostaurin improved survival compared with chemotherapy alone. Therefore, midostaurin was approved to treat adult AML patients with FLT3-ITD in 2017. Gemtuzumab ozogamicin, a selective anti-CD33 antibody-calicheamicin conjugate, is approved for clinical practice. Many molecular targeting agents are now being used for hematological malignancies. |
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| MeSH term(s) | Combined Modality Therapy/methods ; Disease-Free Survival ; Hematologic Neoplasms/etiology ; Hematologic Neoplasms/mortality ; Hematologic Neoplasms/therapy ; Humans ; Immunotherapy, Adoptive/methods ; Molecular Targeted Therapy/methods ; Prognosis ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/immunology ; Randomized Controlled Trials as Topic ; Receptors, Chimeric Antigen/immunology |
| Chemical Substances | Protein Kinase Inhibitors ; Receptors, Chimeric Antigen ; Protein-Tyrosine Kinases (EC 2.7.10.1) |
| Language | English |
| Publishing date | 2019-09-04 |
| Publishing country | Netherlands |
| Document type | Journal Article ; Review |
| ZDB-ID | 80121-5 |
| ISSN | 1879-0712 ; 0014-2999 |
| ISSN (online) | 1879-0712 |
| ISSN | 0014-2999 |
| DOI | 10.1016/j.ejphar.2019.172641 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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