Potential Clinical Uses of CDK Inhibitors: Lessons from Synthetic Lethality Screens

0450910 - ÚEB 2016 RIV US eng J - Článek v odborném periodiku
Vymětalová, Ladislava - Kryštof, Vladimír
Potential Clinical Uses of CDK Inhibitors: Lessons from Synthetic Lethality Screens.
Medicinal Research Reviews. Roč. 35, č. 6 (2015), s. 1156-1174. ISSN 0198-6325. E-ISSN 1098-1128
Grant CEP: GA MŠMT(CZ) LO1204; GA ČR(CZ) GA15-15264S
Institucionální podpora: RVO:61389030
Klíčová slova: cyclin-dependent kinase * inhibitor * cancer
Kód oboru RIV: FR - Farmakologie a lékárnická chemie
Impakt faktor: 9.135, rok: 2015

Developments in genetic and genomic technology have produced vast quantities of data that are gradually yielding new insights into fundamental cellular and molecular processes. In particular, they have revealed some differences between normal and transformed cells that could potentially be exploited to develop targeted, personalized cancer therapies with unprecedented efficiencies. This review summarizes recent findings from synthetic lethality (SL) screens against cyclin-dependent kinases (CDKs) that can be targeted with small molecule kinase inhibitors. SL screens can be used to identify cancers sensitive to CDK inhibitors. Several SL partners of specific CDKs have been identified, including MYC, K-Ras, VHL, PI3K, and PARP, all of which are discussed in the review. CDK inhibitors have been in clinical trials for nearly 20 years and it has become clear that effective therapy using these compounds will require careful selection of patients with respect to the specific molecular phenotype of their disease.
Trvalý link: http://hdl.handle.net/11104/0252096