Hematological malignancies and molecular targeting therapy

Research output: Contribution to journalReview article

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 languageEnglish
Article number172641
JournalEuropean Journal of Pharmacology
Volume862
DOIs
Publication statusPublished - Nov 5 2019

Fingerprint

4'-N-benzoylstaurosporine
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Hematopoietic Stem Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug Therapy
Acute Myeloid Leukemia
Philadelphia Chromosome
Antigen Receptors
Therapeutics
Drug Delivery Systems
Cell- and Tissue-Based Therapy
Cytogenetics
Disease-Free Survival
Molecular Biology
Survival Rate
T-Lymphocytes
Survival
Imatinib Mesylate

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 journalReview article

@article{b66af592d7614ee283fba9c016ee2390,
title = "Hematological malignancies and molecular targeting therapy",
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.",
keywords = "Acute lymphoblastic leukemia, Acute myeloid leukemia, Chronic myeloid leukemia, Molecular targeting therapy, Myeloproliferative neoplasm, Tyrosine kinase inhibitor",
author = "Akira Shimada",
year = "2019",
month = "11",
day = "5",
doi = "10.1016/j.ejphar.2019.172641",
language = "English",
volume = "862",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

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 -