Editing Chemotherapy (section)

== Resistance ==
[[Drug resistance|Resistance]] is a major cause of treatment failure in chemotherapeutic drugs. There are a few possible causes of resistance in cancer, one of which is the presence of small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Cancer cells produce high amounts of these pumps, known as [[p-glycoprotein]], in order to protect themselves from chemotherapeutics. Research on p-glycoprotein and other such chemotherapy efflux pumps is currently ongoing. Medications to inhibit the function of p-glycoprotein are undergoing investigation, but due to toxicities and interactions with anti-cancer drugs their development has been difficult.<ref name="pmid12591977">{{cite journal | vauthors = Goldman B | title = Multidrug resistance: can new drugs help chemotherapy score against cancer? | journal = Journal of the National Cancer Institute | volume = 95 | issue = 4 | pages = 255–7 | date = February 2003 | pmid = 12591977 | doi = 10.1093/jnci/95.4.255 | doi-access = free }}</ref><ref>{{cite book | vauthors = Crowley E, McDevitt CA, Callaghan R |title=Multidrug Resistance in Cancer. Generating Inhibitors of P-Glycoprotein: Where to, Now?|year=2009|publisher=Springer Protocols|pages=405–432}}</ref> Another mechanism of resistance is [[gene duplication|gene amplification]], a process in which multiple copies of a gene are produced by cancer cells. This overcomes the effect of drugs that reduce the expression of genes involved in replication. With more copies of the gene, the drug can not prevent all expression of the gene and therefore the cell can restore its proliferative ability. Cancer cells can also cause defects in the cellular pathways of [[apoptosis]] (programmed cell death). As most chemotherapy drugs kill cancer cells in this manner, defective apoptosis allows survival of these cells, making them resistant. Many chemotherapy drugs also cause DNA damage, which can be repaired by [[enzyme]]s in the cell that carry out [[DNA repair]]. Upregulation of these genes can overcome the DNA damage and prevent the induction of apoptosis. Mutations in genes that produce drug target proteins, such as [[tubulin]], can occur which prevent the drugs from binding to the protein, leading to resistance to these types of drugs.<ref name="pmid16103712">{{cite journal | vauthors = Luqmani YA | title = Mechanisms of drug resistance in cancer chemotherapy | journal = Medical Principles and Practice | volume = 14 | pages = 35–48 | year = 2005 | issue = Suppl 1 | pmid = 16103712 | doi = 10.1159/000086183 | doi-access = free }}</ref> Drugs used in chemotherapy can induce cell stress, which can kill a cancer cell; however, under certain conditions, cells stress can induce changes in gene expression that enables resistance to several types of drugs.<ref>{{cite journal | vauthors = Moschovi M, Critselis E, Cen O, Adamaki M, Lambrou GI, Chrousos GP, Vlahopoulos S | title = Drugs acting on homeostasis: challenging cancer cell adaptation | journal = Expert Review of Anticancer Therapy | volume = 15 | issue = 12 | pages = 1405–17 | year = 2015 | pmid = 26523494 | doi = 10.1586/14737140.2015.1095095 | s2cid = 28992964 }}</ref> In [[lung cancer]], the transcription factor [[NF-κB|NFκB]] is thought to play a role in resistance to chemotherapy, via inflammatory pathways.<ref>{{cite journal | vauthors = Heavey S, Godwin P, Baird AM, Barr MP, Umezawa K, Cuffe S, Finn SP, O'Byrne KJ, Gately K | display-authors = 6 | title = Strategic targeting of the PI3K-NFκB axis in cisplatin-resistant NSCLC | journal = Cancer Biology & Therapy | volume = 15 | issue = 10 | pages = 1367–77 | date = October 2014 | pmid = 25025901 | pmc = 4130730 | doi = 10.4161/cbt.29841 }}</ref><ref>{{cite journal | vauthors = Ryan SL, Beard S, Barr MP, Umezawa K, Heavey S, Godwin P, Gray SG, Cormican D, Finn SP, Gately KA, Davies AM, Thompson EW, Richard DJ, O'Byrne KJ, Adams MN, Baird AM | display-authors = 6 | title = Targeting NF-κB-mediated inflammatory pathways in cisplatin-resistant NSCLC | journal = Lung Cancer | volume = 135 | pages = 217–227 | date = September 2019 | pmid = 31446998 | doi = 10.1016/j.lungcan.2019.07.006 | s2cid = 199025494 | url = https://eprints.qut.edu.au/200933/1/__qut.edu.au_Documents_StaffHome_StaffGroupH%24_henderm5_Desktop_1-s2.0-S016950021930529X-main.pdf }}</ref><ref>{{cite journal | vauthors = Godwin P, Baird AM, Heavey S, Barr MP, O'Byrne KJ, Gately K | title = Targeting nuclear factor-kappa B to overcome resistance to chemotherapy | journal = Frontiers in Oncology | volume = 3 | pages = 120 | date = 2013 | pmid = 23720710 | pmc = 3655421 | doi = 10.3389/fonc.2013.00120 | doi-access = free }}</ref>