Počet záznamů: 1
BH3 Mimetics in Hematologic Malignancies
- 1.
SYSNO ASEP 0550596 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název BH3 Mimetics in Hematologic Malignancies Tvůrce(i) Klener, P. (CZ)
Sovilj, Dana (BTO-N)
Renesova, N. (CZ)
Anděra, Ladislav (BTO-N)Celkový počet autorů 4 Číslo článku 10157 Zdroj.dok. International Journal of Molecular Sciences. - : MDPI
Roč. 22, č. 18 (2021)Poč.str. 25 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova apoptosis ; venetoclax ; BH3 mimetics ; hematologic malignancies Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology CEP NU21-03-00386 GA MZd - Ministerstvo zdravotnictví GA19-08772S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora BTO-N - RVO:86652036 UT WOS 000700750400001 EID SCOPUS 85115139187 DOI 10.3390/ijms221810157 Anotace Hematologic malignancies (HM) comprise diverse cancers of lymphoid and myeloid origin, including lymphomas (approx. 40%), chronic lymphocytic leukemia (CLL, approx. 15%), multiple myeloma (MM, approx. 15%), acute myeloid leukemia (AML, approx. 10%), and many other diseases. Despite considerable improvement in treatment options and survival parameters in the new millennium, many patients with HM still develop chemotherapy-refractory diseases and require re-treatment. Because frontline therapies for the majority of HM (except for CLL) are still largely based on classical cytostatics, the relapses are often associated with defects in DNA damage response (DDR) pathways and anti-apoptotic blocks exemplified, respectively, by mutations or deletion of the TP53 tumor suppressor, and overexpression of anti-apoptotic proteins of the B-cell lymphoma 2 (BCL2) family. BCL2 homology 3 (BH3) mimetics represent a novel class of pro-apoptotic anti-cancer agents with a unique mode of action-direct targeting of mitochondria independently of TP53 gene aberrations. Consequently, BH3 mimetics can effectively eliminate even non-dividing malignant cells with adverse molecular cytogenetic alterations. Venetoclax, the nanomolar inhibitor of BCL2 anti-apoptotic protein has been approved for the therapy of CLL and AML. Numerous venetoclax-based combinatorial treatment regimens, next-generation BCL2 inhibitors, and myeloid cell leukemia 1 (MCL1) protein inhibitors, which are another class of BH3 mimetics with promising preclinical results, are currently being tested in several clinical trials in patients with diverse HM. These pivotal trials will soon answer critical questions and concerns about these innovative agents regarding not only their anti-tumor efficacy but also potential side effects, recommended dosages, and the optimal length of therapy as well as identification of reliable biomarkers of sensitivity or resistance. Effective harnessing of the full therapeutic potential of BH3 mimetics is a critical mission as it may directly translate into better management of the aggressive forms of HM and could lead to significantly improved survival parameters and quality of life in patients with urgent medical needs. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2022 Elektronická adresa https://www.mdpi.com/1422-0067/22/18/10157
Počet záznamů: 1