Editing Chemotherapy (section)

== Mechanism of action ==
[[File:Cell cycle simple.png|thumb|The four phases of the cell cycle. G1 – the initial growth phase. S – the phase in which DNA is synthesised. G2 – the second growth phase in preparation for cell division. M – mitosis; where the cell divides to produce two daughter cells that continue the cell cycle.]]
[[Cancer]] is the uncontrolled growth of [[cell (biology)|cells]] coupled with [[malignant]] behaviour: invasion and [[metastasis]] (among other features).<ref name="pmid10647931">{{cite journal | vauthors = Hanahan D, Weinberg RA | title = The hallmarks of cancer | journal = Cell | volume = 100 | issue = 1 | pages = 57–70 | date = January 2000 | pmid = 10647931 | doi = 10.1016/S0092-8674(00)81683-9 | s2cid = 1478778 | doi-access = free }}</ref> It is caused by the interaction between [[gene]]tic susceptibility and environmental factors.<ref name="pmid18196605">{{cite journal | vauthors = Hodgson S | title = Mechanisms of inherited cancer susceptibility | journal = Journal of Zhejiang University Science B | volume = 9 | issue = 1 | pages = 1–4 | date = January 2008 | pmid = 18196605 | pmc = 2170461 | doi = 10.1631/jzus.B073001 }}</ref><ref name="pmid9353182">{{cite journal | vauthors = Perera FP | title = Environment and cancer: who are susceptible? | journal = Science | volume = 278 | issue = 5340 | pages = 1068–73 | date = November 1997 | pmid = 9353182 | doi = 10.1126/science.278.5340.1068 | bibcode = 1997Sci...278.1068P }}</ref> These factors lead to accumulations of [[genetic mutation]]s in [[oncogene]]s (genes that control the growth rate of cells) and [[tumor suppressor gene]]s (genes that help to prevent cancer), which gives cancer cells their malignant characteristics, such as uncontrolled growth.<ref>{{cite book |editor1-last=Hoskins |editor1-first=William J. |editor2-last=Perez |editor2-first=Carlos A. |editor3-last=Young|editor3-first=Robert C.|editor4-last=Barakat|editor4-first=Richard R.|editor5-last=Markman|editor5-first=Maurie|editor6-last=Randall|editor6-first=Marcus E. | name-list-style = vanc |title=Principles and practice of gynecologic oncology|date=2005|publisher=Lippincott Williams & Wilkins|location=Baltimore, Md.|isbn=978-0-7817-4689-2|edition = 4th }}</ref>{{rp|93–94}}

In the broad sense, most chemotherapeutic drugs work by impairing [[mitosis]] ([[cell division]]), effectively targeting [[fast-dividing cells]]. As these drugs cause damage to cells, they are termed ''cytotoxic''. They prevent mitosis by various mechanisms including damaging DNA and inhibition of the cellular machinery involved in cell division.<ref name="pmid14508075">{{cite journal | vauthors = Malhotra V, Perry MC | title = Classical chemotherapy: mechanisms, toxicities and the therapeutic window | journal = Cancer Biology & Therapy | volume = 2 | issue = 4 Suppl 1 | pages = S2-4 | year = 2003 | pmid = 14508075 | doi = 10.4161/cbt.199 | doi-access = free }}</ref><ref name="pmid19651324">{{cite journal | vauthors = Kehe K, Balszuweit F, Steinritz D, Thiermann H | title = Molecular toxicology of sulfur mustard-induced cutaneous inflammation and blistering | journal = Toxicology | volume = 263 | issue = 1 | pages = 12–9 | date = September 2009 | pmid = 19651324 | doi = 10.1016/j.tox.2009.01.019 | bibcode = 2009Toxgy.263...12K }}</ref> One theory as to why these drugs kill cancer cells is that they induce a programmed form of cell death known as [[apoptosis]].<ref name="pmid10928287">{{cite journal | vauthors = Makin G, Hickman JA | title = Apoptosis and cancer chemotherapy | journal = Cell and Tissue Research | volume = 301 | issue = 1 | pages = 143–52 | date = July 2000 | pmid = 10928287 | doi = 10.1007/s004419900160 | bibcode = 1994RSPTB.345..319H | s2cid = 22909070 }}</ref>

As chemotherapy affects cell division, tumors with high [[proliferative index|growth rates]] (such as [[acute myelogenous leukemia]] and the aggressive [[lymphoma]]s, including [[Hodgkin's disease]]) are more sensitive to chemotherapy, as a larger proportion of the targeted cells are undergoing [[cell division]] at any time.  Malignancies with slower growth rates, such as indolent lymphomas, tend to respond to chemotherapy much more modestly.<ref name=Corrie>{{cite journal|last1=Corrie PG|title=Cytotoxic chemotherapy: clinical aspects|journal=Medicine|year=2008|volume=36|issue=1|pages=24–28|doi=10.1016/j.mpmed.2007.10.012|first1=Pippa G.}}</ref> [[Tumour heterogeneity|Heterogeneic tumours]] may also display varying sensitivities to chemotherapy agents, depending on the subclonal populations within the tumor.<ref>{{Cite journal |last1=Fisher |first1=R |last2=Pusztai |first2=L |last3=Swanton |first3=C |date=2013-02-19 |title=Cancer heterogeneity: implications for targeted therapeutics |journal=British Journal of Cancer |volume=108 |issue=3 |pages=479–485 |doi=10.1038/bjc.2012.581 |issn=0007-0920 |pmc=3593543 |pmid=23299535}}</ref>

Cells from the [[immune system]] also make crucial contributions to the antitumor effects of chemotherapy.<ref>{{cite journal | vauthors = Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G | title = Immunological aspects of cancer chemotherapy | journal = Nature Reviews. Immunology | volume = 8 | issue = 1 | pages = 59–73 | date = January 2008 | pmid = 18097448 | doi = 10.1038/nri2216 | s2cid = 205490545 | doi-access = free }}</ref> For example, the chemotherapeutic drugs [[oxaliplatin]] and [[cyclophosphamide]] can cause tumor cells to die in a way that is detectable by the immune system (called [[immunogenic cell death]]), which mobilizes immune cells with antitumor functions.<ref>{{cite journal | vauthors = Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G | title = Immunogenic cell death in cancer and infectious disease | journal = Nature Reviews. Immunology | volume = 17 | issue = 2 | pages = 97–111 | date = February 2017 | pmid = 27748397 | doi = 10.1038/nri.2016.107 | s2cid = 4045072 }}</ref> Chemotherapeutic drugs that cause cancer immunogenic tumor cell death can make unresponsive tumors sensitive to [[immune checkpoint]] therapy.<ref>{{cite journal | vauthors = Pfirschke C, Engblom C, Rickelt S, Cortez-Retamozo V, Garris C, Pucci F, Yamazaki T, Poirier-Colame V, Newton A, Redouane Y, Lin YJ, Wojtkiewicz G, Iwamoto Y, Mino-Kenudson M, Huynh TG, Hynes RO, Freeman GJ, Kroemer G, Zitvogel L, Weissleder R, Pittet MJ | title = Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy | journal = Immunity | volume = 44 | issue = 2 | pages = 343–54 | date = February 2016 | pmid = 26872698 | pmc = 4758865 | doi = 10.1016/j.immuni.2015.11.024 }}</ref>