title: Circadian clock: Time for novel anticancer strategies?
abstract: Disruption of the circadian clock is associated with a variety of human pathologies, including cancer. Rather than being a mere consequence of a global changes associated with the cancer cell transcriptome, the aberrant clock gene expression observed in many tumors may serve for cancer cell survival. This scenario suggests the provocative hypothesis that pharmacological modulation of clock-related proteins may be suitable as an effective anticancer strategy. In this review, we focus on the functions of the druggable circadian nuclear receptors, REV-ERBα and REV-ERBβ, in cancer cell survival and describe the potential development of small molecule compounds that modulate REV-ERB activity as novel anticancer therapeutics. In addition, we debate the use of circadian rhythm-based synthetic lethal approaches to identify yet unexplored anticancer strategies.
authors: Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors: Luisa
authors: L
authors: Ercolani
authors: Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors: Alessio
authors: A
authors: Ferrari
authors: Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors: Claudia
authors: C
authors: De Mei
authors: Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
authors: Chiara
authors: C
authors: Parodi
authors: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia, Via Adamello 16, 20139 Milano, Italy. Electronic address: mark.wade@iit.it.
authors: Mark
authors: M
authors: Wade
authors: Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy. Electronic address: benedetto.grimaldi@iit.it.
authors: Benedetto
authors: B
authors: Grimaldi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D057906:Circadian Clocks / Q000187:drug effects* / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D054852:Small Molecule Libraries
keywords: ARN5187; Anticancer agents; Autophagy; Cancer; Circadian; Combined anticancer strategy; Dual inhibitor; Lysosomotropic agents; Metabolism; Nuclear receptors; REV-ERB; REV-ERB agonist; REV-ERB antagonist; SR9011