Editing G2 phase (section)

== Medical relevance ==
Mutations in several genes involved in the G2/M transition are implicated in many cancers. Overexpression of both cyclin B and CDK1, oftentimes downstream of loss of [[Tumor suppressor|tumor suppressors]] such as p53, can cause an increase in cell proliferation.<ref name=":0" /> Experimental approaches to mitigate these changes include both pharmacological inhibition of CDK1 and downregulation of cyclin B1 expression (e.g., via [[Small interfering RNA|siRNA]]).<ref>{{cite journal | vauthors = Asghar U, Witkiewicz AK, Turner NC, Knudsen ES | title = The history and future of targeting cyclin-dependent kinases in cancer therapy | journal = Nature Reviews. Drug Discovery | volume = 14 | issue = 2 | pages = 130–46 | date = February 2015 | pmid = 25633797 | pmc = 4480421 | doi = 10.1038/nrd4504 }}</ref><ref>{{cite journal | vauthors = Androic I, Krämer A, Yan R, Rödel F, Gätje R, Kaufmann M, Strebhardt K, Yuan J | display-authors = 6 | title = Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol | journal = BMC Cancer | volume = 8 | issue = 1 | pages = 391 | date = December 2008 | pmid = 19113992 | pmc = 2639606 | doi = 10.1186/1471-2407-8-391 | doi-access = free }}</ref> 

Other attempts to modulate the G2/M transition for chemotherapy applications have focused on the DNA damage checkpoint. Pharmacologically bypassing the G2/M checkpoint via inhibition of Chk1  has been shown to enhance cytotoxicity of other chemotherapy drugs. Bypassing the checkpoint leads to the rapid accumulation of deleterious mutations, which is thought to drive the cancerous cells into [[apoptosis]]. Conversely, attempts to prolong the G2/M arrest have also been shown to enhance the cytotoxicity of drugs like [[doxorubicin]]. These approaches remain in clinical and pre-clinical phases of research.<ref>{{cite journal | vauthors = DiPaola RS | title = To arrest or not to G(2)-M Cell-cycle arrest : commentary re: A. K. Tyagi et al., Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth inhibition, G(2)-M arrest, and apoptosis. Clin. cancer res., 8: 3512-3519, 2002 | journal = Clinical Cancer Research | volume = 8 | issue = 11 | pages = 3311–4 | date = November 2002 | pmid = 12429616 | url = https://clincancerres.aacrjournals.org/content/8/11/3311 }}</ref>