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.
| Original language | English |
|---|---|
| Article number | 172641 |
| Journal | European Journal of Pharmacology |
| Volume | 862 |
| DOIs | |
| Publication status | Published - Nov 5 2019 |
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Keywords
- Acute lymphoblastic leukemia
- Acute myeloid leukemia
- Chronic myeloid leukemia
- Molecular targeting therapy
- Myeloproliferative neoplasm
- Tyrosine kinase inhibitor
ASJC Scopus subject areas
- Pharmacology
Cite this
Hematological malignancies and molecular targeting therapy. / Shimada, Akira.
In: European Journal of Pharmacology, Vol. 862, 172641, 05.11.2019.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Hematological malignancies and molecular targeting therapy
AU - Shimada, Akira
PY - 2019/11/5
Y1 - 2019/11/5
N2 - 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.
AB - 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.
KW - Acute lymphoblastic leukemia
KW - Acute myeloid leukemia
KW - Chronic myeloid leukemia
KW - Molecular targeting therapy
KW - Myeloproliferative neoplasm
KW - Tyrosine kinase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85071986734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071986734&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2019.172641
DO - 10.1016/j.ejphar.2019.172641
M3 - Review article
C2 - 31493406
AN - SCOPUS:85071986734
VL - 862
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
M1 - 172641
ER -