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@article{1720316,
author = {Boudný, Miroslav and Trbušek, Martin},
article_location = {OXFORD},
article_number = {AUG},
doi = {http://dx.doi.org/10.1016/j.ctrv.2020.102026},
keywords = {DDR; ATR; CHK1; Inhibition; Leukemia},
language = {eng},
issn = {0305-7372},
journal = {CANCER TREATMENT REVIEWS},
title = {ATR-CHK1 pathway as a therapeutic target for acute and chronic leukemias},
url = {https://www.sciencedirect.com/science/article/pii/S0305737220300645?via%3Dihub},
volume = {88},
year = {2020}
}
TY - JOUR
ID - 1720316
AU - Boudný, Miroslav - Trbušek, Martin
PY - 2020
TI - ATR-CHK1 pathway as a therapeutic target for acute and chronic leukemias
JF - CANCER TREATMENT REVIEWS
VL - 88
IS - AUG
SP - 102026
EP - 102026
PB - ELSEVIER SCI LTD
SN - 03057372
KW - DDR
KW - ATR
KW - CHK1
KW - Inhibition
KW - Leukemia
UR - https://www.sciencedirect.com/science/article/pii/S0305737220300645?via%3Dihub
L2 - https://www.sciencedirect.com/science/article/pii/S0305737220300645?via%3Dihub
N2 - Progress in cancer therapy changed the outcome of many patients and moved therapy from chemotherapy agents to targeted drugs. Targeted drugs already changed the clinical practice in treatment of leukemias, such as imatinib (BCR/ABL inhibitor) in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), ibrutinib (Bruton's tyrosine kinase inhibitor) in chronic lymphocytic leukemia (CLL), venetoclax (BCL2 inhibitor) in CLL and acute myeloid leukemia (AML) or midostaurin (FLT3 inhibitor) in AML. In this review, we focused on DNA damage response (DDR) inhibition, specifically on inhibition of ATR-CHK1 pathway. Cancer cells harbor often defects in different DDR pathways, which render them vulnerable to DDR inhibition. Some DDR inhibitors showed interesting single-agent activity even in the absence of cytotoxic drug especially in cancers with underlying defects in DDR or DNA replication. Almost no mutations were found in ATR and CHEK1 genes in leukemia patients. Together with the fact that ATR-CHK1 pathway is essential for cell development and survival of leukemia cells, it represents a promising therapeutic target for treatment of leukemia. ATR-CHK1 inhibition showed excellent results in preclinical testing in acute and chronic leukemias. However, results in clinical trials are so far insufficient. Therefore, the ongoing and future clinical trials will decide on the success of ATR/CHK1 inhibitors in clinical practice of leukemia treatment.
ER -
BOUDNÝ, Miroslav a Martin TRBUŠEK. ATR-CHK1 pathway as a therapeutic target for acute and chronic leukemias. \textit{CANCER TREATMENT REVIEWS}. OXFORD: ELSEVIER SCI LTD, 2020, roč.~88, AUG, s.~102026-102037. ISSN~0305-7372. Dostupné z: https://dx.doi.org/10.1016/j.ctrv.2020.102026.
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