Editing Chemotherapy (section)

==== Anti-microtubule agents ====
[[File:Microtubules and alkaloids.png|thumb|left|''Vinca'' alkaloids prevent the assembly of microtubules, whereas taxanes prevent their disassembly. Both mechanisms cause defective mitosis.]]
[[Anti-microtubule agent]]s are [[plant]]-derived chemicals that block cell division by preventing [[microtubule]] function. Microtubules are an important cellular structure composed of two proteins, [[α-tubulin]] and [[β-tubulin]]. They are hollow, rod-shaped structures that are required for cell division, among other cellular functions.<ref name="pmid1687171">{{cite journal | vauthors = Rowinsky EK, Donehower RC | title = The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics | journal = Pharmacology & Therapeutics | volume = 52 | issue = 1 | pages = 35–84 | date = October 1991 | pmid = 1687171 | doi = 10.1016/0163-7258(91)90086-2 }}</ref> Microtubules are dynamic structures, which means that they are permanently in a state of assembly and disassembly. [[Vinca alkaloid|''Vinca'' alkaloids]] and [[taxane]]s are the two main groups of anti-microtubule agents, and although both of these groups of drugs cause microtubule dysfunction, their mechanisms of action are completely opposite: ''Vinca'' alkaloids prevent the assembly of microtubules, whereas taxanes prevent their disassembly. By doing so, they can induce [[mitotic catastrophe]] in the cancer cells.<ref>{{Cite journal |last1=Vitale |first1=Ilio |last2=Galluzzi |first2=Lorenzo |last3=Castedo |first3=Maria |last4=Kroemer |first4=Guido |date=June 2011 |title=Mitotic catastrophe: a mechanism for avoiding genomic instability |url=https://www.nature.com/articles/nrm3115 |journal=Nature Reviews Molecular Cell Biology |language=en |volume=12 |issue=6 |pages=385–392 |doi=10.1038/nrm3115 |pmid=21527953 |s2cid=22483746 |issn=1471-0072}}</ref>  Following this, cell cycle arrest occurs, which induces programmed cell death ([[apoptosis]]).<ref name=lind /><ref name="pmid20577942" /> These drugs can also affect [[Angiogenesis|blood vessel growth]], an essential process that tumours utilise in order to grow and metastasise.<ref name="pmid20577942">{{cite journal | vauthors = Yue QX, Liu X, Guo DA | title = Microtubule-binding natural products for cancer therapy | journal = Planta Medica | volume = 76 | issue = 11 | pages = 1037–43 | date = August 2010 | pmid = 20577942 | doi = 10.1055/s-0030-1250073 | doi-access = free | bibcode = 2010PlMed..76.1037Y }}</ref>

''Vinca'' alkaloids are derived from the [[Madagascar periwinkle]], ''Catharanthus roseus'',<ref>{{cite book|vauthors = Hirata K, Miyamoto K, Miura Y|chapter = ''Catharanthus roseus'' L. (Periwinkle): Production of Vindoline and Catharanthine in Multiple Shoot Cultures|title = Biotechnology in Agriculture and Forestry 26|series = Medicinal and Aromatic Plants|volume = VI|veditors = Bajaj YP|publisher = [[Springer-Verlag]]|year = 1994|pages = [https://archive.org/details/medicinalaromati0006unse/page/46 46–55]|chapter-url = https://books.google.com/books?id=e64hCDBddowC&pg=PA47|isbn = 9783540563914|url = https://archive.org/details/medicinalaromati0006unse/page/46}}</ref><ref>{{cite journal | vauthors = van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R | title = The Catharanthus alkaloids: pharmacognosy and biotechnology | journal = Current Medicinal Chemistry | volume = 11 | issue = 5 | pages = 607–28 | date = March 2004 | pmid = 15032608 | doi = 10.2174/0929867043455846 }}</ref> formerly known as ''Vinca rosea''. They bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules. The original ''vinca'' alkaloids are [[natural product]]s that include [[vincristine]] and [[vinblastine]].<ref>{{cite book|title = Metal Catalyzed Reductive C—C Bond Formation: A Departure from Preformed Organometallic Reagents|volume = 279|series = Topics in Current Chemistry|pages = 25–52|year = 2007|chapter = Reductive C—C bond formation after epoxide opening via electron transfer| vauthors = Gansäuer A, Justicia J, Fan CA, Worgull D, Piestert F |doi = 10.1007/128_2007_130|chapter-url = https://books.google.com/books?id=A5xcVmT9iIQC&pg=PA25|editor-link1=Michael J. Krische|editor-first = Michael J.|editor-last = Krische|publisher = [[Springer Science & Business Media]]|isbn = 9783540728795}}</ref><ref>{{cite book|chapter = Africa's gift to the world|pages = 46–51|chapter-url = https://books.google.com/books?id=aXGmCwAAQBAJ&pg=PA46|title = Botanical Miracles: Chemistry of Plants That Changed the World|first1 = Raymond|last1 = Cooper|first2 = Jeffrey John|last2 = Deakin | name-list-style = vanc |publisher = [[CRC Press]]|year = 2016|isbn = 9781498704304}}</ref><ref name = MoleculesReview>{{cite journal | vauthors = Keglevich P, Hazai L, Kalaus G, Szántay C | title = Modifications on the basic skeletons of vinblastine and vincristine | journal = Molecules | volume = 17 | issue = 5 | pages = 5893–914 | date = May 2012 | pmid = 22609781 | pmc = 6268133 | doi = 10.3390/molecules17055893 | doi-access = free }}</ref><ref>{{cite book|last = Raviña|first = Enrique|title = The evolution of drug discovery: From traditional medicines to modern drugs|year = 2011|publisher = [[John Wiley & Sons]]|isbn = 9783527326693|pages = 157–159|chapter = Vinca alkaloids|chapter-url = https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA157}}</ref> Following the success of these drugs, semi-synthetic ''vinca'' alkaloids were produced: [[vinorelbine]] (used in the treatment of [[non-small-cell lung cancer]]<ref name = MoleculesReview /><ref>{{cite journal | vauthors = Faller BA, Pandit TN | title = Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer | journal = Clinical Medicine Insights: Oncology | volume = 5 | pages = 131–44 | year = 2011 | pmid = 21695100 | pmc = 3117629 | doi = 10.4137/CMO.S5074 }}</ref><ref>{{cite journal | vauthors = Ngo QA, Roussi F, Cormier A, Thoret S, Knossow M, Guénard D, Guéritte F | title = Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 1 | pages = 134–42 | date = January 2009 | pmid = 19072542 | doi = 10.1021/jm801064y }}</ref>), [[vindesine]], and [[vinflunine]].<ref name="pmid20577942" /> These drugs are [[cell cycle]]-specific. They bind to the tubulin molecules in [[S-phase]] and prevent proper microtubule formation required for [[M-phase]].<ref name="pmid14508075" />

Taxanes are natural and semi-synthetic drugs. The first drug of their class, [[paclitaxel]], was originally extracted from ''[[Taxus brevifolia]]'', the Pacific yew. Now this drug and another in this class, [[docetaxel]], are produced semi-synthetically from a chemical found in the bark of another yew tree, ''[[Taxus baccata]]''.<ref>{{Cite journal |last1=Croteau |first1=Rodney |last2=Ketchum |first2=Raymond E. B. |last3=Long |first3=Robert M. |last4=Kaspera |first4=Rüdiger |last5=Wildung |first5=Mark R. |date=2006 |title=Taxol biosynthesis and molecular genetics |journal=Phytochemistry Reviews |volume=5 |issue=1 |pages=75–97 |doi=10.1007/s11101-005-3748-2 |issn=1568-7767 |pmc=2901146 |pmid=20622989|bibcode=2006PChRv...5...75C }}</ref>

[[Podophyllotoxin]] is an antineoplastic [[lignan]] obtained primarily from the [[Podophyllum|American mayapple]] (''Podophyllum peltatum'') and [[Sinopodophyllum|Himalayan mayapple]] (''Sinopodophyllum hexandrum''). It has anti-microtubule activity, and its mechanism is similar to that of ''vinca'' alkaloids in that they bind to tubulin, inhibiting microtubule formation. Podophyllotoxin is used to produce two other drugs with different mechanisms of action: [[etoposide]] and [[teniposide]].<ref name="pmid9562603">{{cite journal | vauthors = Damayanthi Y, Lown JW | title = Podophyllotoxins: current status and recent developments | journal = Current Medicinal Chemistry | volume = 5 | issue = 3 | pages = 205–52 | date = June 1998 | doi = 10.2174/0929867305666220314204426 | pmid = 9562603 | s2cid = 247493530 }}</ref><ref>{{cite journal |vauthors=Liu YQ, Yang L, Tian X |title=Podophyllotoxin: current perspectives |journal=Current Bioactive Compounds |year=2007 |volume=3 |issue=1 |pages=37–66 |doi=10.1016/j.jallcom.2006.06.070 }}</ref>