Citation

Visconti R, Della Monica R, Grieco D. Journal of Experimental and Clinical Cancer Research 2016; 35(1).

Copyright

(Copyright © 2016)

DOI

10.1186/s13046-016-0433-9

PMID

unavailable

Abstract

Major currently used anticancer therapeutics either directly damage DNA or target and upset basic cell division mechanisms like DNA replication and chromosome segregation. These insults elicit activation of cell cycle checkpoints, safeguard mechanisms that cells implement to correctly complete cell cycle phases, repair damage or eventually commit suicide in case damage is unrepairable. Although cancer cells appear to be advantageously defective in some aspects of checkpoint physiology, recent acquisitions on the biochemical mechanisms of the various checkpoints are offering new therapeutic approaches against cancer. Indeed, chemical manipulation of these mechanisms is providing new therapeutic strategies and tools to increase the killing efficacy of major cancer therapeutics as well as to directly promote cancer cell death. In this review we summarize developing concepts on how targeting cell cycle checkpoints may provide substantial improvement to cancer therapy. © 2016 The Author(s).

Language: en

Keywords

human; Review; DNA; apoptosis; unclassified drug; neutropenia; priority journal; vincristine; nonhuman; leukemia; drug potentiation; peripheral neuropathy; malignant neoplastic disease; cisplatin; paclitaxel; bone marrow suppression; blood toxicity; unspecified side effect; supraventricular tachycardia; doxorubicin; antineoplastic activity; solid tumor; drug targeting; fluorouracil; gemcitabine; cytarabine; drug protein binding; DNA damage; vinblastine; docetaxel; cancer inhibition; cancer therapy; taxane derivative; Vinca alkaloid; target cell; phase 2 clinical trial (topic); phase 1 clinical trial (topic); 2 allyl 1 [6 (1 hydroxy 1 methylethyl) 2 pyridinyl] 6 [4 (4 methyl 1 piperazinyl)anilino] 1h pyrazolo[3,4 d]pyrimidin 3(2h) one; 7 hydroxystaurosporine; ATR protein; beta tubulin; Cancer drug; cell cycle arrest; cell cycle checkpoint; Cell cycle checkpoint; checkpoint kinase 2; Chk1; DNA damage response; DNA synthesis inhibition; Fcp1; G1 phase cell cycle checkpoint; G2 phase cell cycle checkpoint; M phase cell cycle checkpoint; Mitosis; nu 6027; protein kinase; protein kinase inhibitor; protein Wee1; S phase cell cycle checkpoint; sch 900776; Spindle assembly checkpoint; Taxane; Vinca alkaloids; Wee1