Editing Cell cycle (section)

==== Synthetic ====

Synthetic inhibitors of [[Cdc25]] could also be useful for the arrest of cell cycle and therefore be useful as antineoplastic and anticancer agents.<ref name="ref 1">{{cite web |url=http://pharmaxchange.info/presentations/cdc25.html |title=Presentation on CDC25 PHOSPHATASES: A Potential Target for Novel Anticancer Agents |access-date=11 March 2010 |archive-url=https://web.archive.org/web/20160303231929/http://pharmaxchange.info/presentations/cdc25.html |archive-date=3 March 2016 |url-status=dead}}</ref>

Many human cancers possess the hyper-activated Cdk 4/6 activities.<ref>{{cite journal | vauthors = Sherr CJ, Beach D, Shapiro GI | title = Targeting CDK4 and CDK6: From Discovery to Therapy | journal = Cancer Discovery | volume = 6 | issue = 4 | pages = 353–367 | date = April 2016 | pmid = 26658964 | pmc = 4821753 | doi = 10.1158/2159-8290.cd-15-0894 }}</ref> Given the observations of cyclin D-Cdk 4/6 functions, inhibition of Cdk 4/6 should result in preventing a malignant tumor from proliferating. Consequently, scientists have tried to invent the synthetic Cdk4/6 inhibitor as Cdk4/6 has been characterized to be a therapeutic target for anti-tumor effectiveness. Three Cdk4/6 inhibitors – [[palbociclib]], [[ribociclib]], and [[abemaciclib]] – currently received FDA approval for clinical use to treat advanced-stage or [[Metastatic breast cancer|metastatic]], [[Hormone receptor positive breast tumor|hormone-receptor-positive]] (HR-positive, HR+), [[HER2 negative breast cancer|HER2-negative]] (HER2-) breast cancer.<ref>{{cite journal | vauthors = O'Leary B, Finn RS, Turner NC | title = Treating cancer with selective CDK4/6 inhibitors | journal = Nature Reviews. Clinical Oncology | volume = 13 | issue = 7 | pages = 417–430 | date = July 2016 | pmid = 27030077 | doi = 10.1038/nrclinonc.2016.26 | s2cid = 23646632 }}</ref><ref name="Bilgin_2017">{{cite journal | vauthors = Bilgin B, Sendur MA, Şener Dede D, Akıncı MB, Yalçın B | title = A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer | journal = Current Medical Research and Opinion | volume = 33 | issue = 9 | pages = 1559–1569 | date = September 2017 | pmid = 28657360 | doi = 10.1080/03007995.2017.1348344 | s2cid = 205542255 }}</ref> For example, palbociclib is an orally active CDK4/6 inhibitor which has demonstrated improved outcomes for ER-positive/HER2-negative advanced breast cancer.  The main side effect is [[neutropenia]] which can be managed by dose reduction.<ref name="Schmidt_2018">{{cite book | vauthors = Schmidt M, Sebastian M | title = Small Molecules in Oncology | chapter = Palbociclib—The First of a New Class of Cell Cycle Inhibitors | series = Recent Results in Cancer Research | volume = 211 | pages = 153–175 | date = August 2018 | pmid = 30069766 | doi = 10.1007/978-3-319-91442-8_11 | isbn = 978-3-319-91441-1 }}</ref>

Cdk4/6 targeted therapy will only treat cancer types where Rb is expressed. Cancer cells with loss of Rb have primary resistance to Cdk4/6 inhibitors.