Editing Chemotherapy (section)

=== Types ===
[[File:Cross-linked DNA by nitrogen mustard.png|thumb|left| Two DNA bases that are cross-linked by a nitrogen mustard. Different nitrogen mustards will have different chemical groups (R). The nitrogen mustards most commonly alkylate the N7 nitrogen of guanine (as shown here) but other atoms can be alkylated.<ref name =Siddik />]]

==== Alkylating agents ====
{{Main|Alkylating antineoplastic agent}}
Alkylating agents are the oldest group of chemotherapeutics in use today. Originally derived from [[mustard gas]] used in [[World War I]], there are now many types of alkylating agents in use.<ref name=Corrie /> They are so named because of their ability to [[alkylation|alkylate]] many molecules, including [[protein]]s, [[RNA]] and [[DNA]]. This ability to bind [[covalent bond|covalently]] to DNA via their [[alkyl group]] is the primary cause for their anti-cancer effects.<ref name=lind>{{cite journal|last1=Lind M.J.|title=Principles of cytotoxic chemotherapy|journal=Medicine|year=2008|volume=36|issue=1|pages=19–23|doi=10.1016/j.mpmed.2007.10.003|first1=M.J.}}</ref> DNA is made of two strands and the molecules may either bind twice to one strand of DNA (intrastrand crosslink) or may bind once to both strands (interstrand crosslink). If the cell tries to replicate crosslinked DNA during [[cell division]], or tries to repair it, the DNA strands can break. This leads to a form of programmed cell death called [[apoptosis]].<ref name =Siddik>{{cite book | vauthors = Siddik ZH |year=2005|publisher=John Wiley & Sons, Ltd|doi=10.1002/0470025077.chap84b|title=The Cancer Handbook|isbn=978-0470025062|chapter=Mechanisms of Action of Cancer Chemotherapeutic Agents: DNA-Interactive Alkylating Agents and Antitumour Platinum-Based Drugs}}</ref><ref name="pmid19002790" /> Alkylating agents will work at any point in the cell cycle and thus are known as cell cycle-independent drugs. For this reason, the effect on the cell is dose dependent; the fraction of cells that die is directly proportional to the dose of drug.<ref name="pmid14508075" />

The subtypes of alkylating agents are the [[nitrogen mustard]]s, [[nitrosoureas]], [[tetrazine]]s, [[aziridines]],<ref>{{cite journal | vauthors = Giorgi-Renault S, Renault J, Baron M, Gebel-Servolles P, Delic J, Cros S, Paoletti C | year = 1988 | title = Heterocyclic quinones XIII. Dimerization in the series of 5,8-quinazolinediones: Synthesis and anti tumor effects of bis(4-amino-5,8-quinazolinediones) | journal = Chem. Pharm. Bull. | volume = 36 | issue = 10| pages = 3933–3947 | doi=10.1248/cpb.36.3933| pmid = 3245973 | doi-access = free }}</ref> [[cisplatin]]s and derivatives, and non-classical alkylating agents. Nitrogen mustards include [[mechlorethamine]], [[cyclophosphamide]], [[melphalan]], [[chlorambucil]], [[ifosfamide]] and [[busulfan]]. Nitrosoureas include [[N-Nitroso-N-methylurea]] (MNU), [[carmustine]] (BCNU), [[lomustine]] (CCNU) and [[semustine]] (MeCCNU), [[fotemustine]] and [[streptozotocin]]. Tetrazines include [[dacarbazine]], [[mitozolomide]] and [[temozolomide]]. Aziridines include [[thiotepa]], [[mytomycin]] and diaziquone (AZQ). Cisplatin and derivatives include [[cisplatin]], [[carboplatin]] and [[oxaliplatin]].<ref name=lind /><ref name="pmid19002790">{{cite journal | vauthors = Damia G, D'Incalci M | title = Mechanisms of resistance to alkylating agents | journal = Cytotechnology | volume = 27 | issue = 1–3 | pages = 165–73 | date = September 1998 | pmid = 19002790 | pmc = 3449574 | doi = 10.1023/A:1008060720608 }}</ref> They impair cell function by forming [[covalent bond]]s with the [[amino group|amino]], [[carboxyl group|carboxyl]], [[sulfhydryl group|sulfhydryl]], and [[phosphate group]]s in biologically important molecules.<ref name=takimoto>{{cite book | vauthors = Takimoto CH, Calvo E | chapter-url = http://www.cancernetwork.com/cancer-management-11/chapter03/article/10165/1402628 | chapter = Principles of Oncologic Pharmacotherapy | veditors = Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ | title = Cancer Management: A Multidisciplinary Approach | edition = 11th | date = 2008 | access-date = 18 June 2009 | archive-date = 15 May 2009 | archive-url = https://web.archive.org/web/20090515221337/http://www.cancernetwork.com/cancer-management-11/chapter03/article/10165/1402628 | url-status = dead }}</ref> Non-classical alkylating agents include [[procarbazine]] and hexamethylmelamine.<ref name=lind /><ref name="pmid19002790" />

==== Antimetabolites ====
[[File:Deoxcytidine, Gemcitidine and Decitabine.png|thumb|[[Deoxycytidine]] (left) and two anti-metabolite drugs (center and right), [[gemcitabine]] and [[decitabine]]. The drugs are very similar but they have subtle differences in their [[chemical structure]].]]
{{Main|Antimetabolite}}
[[Anti-metabolite]]s are a group of molecules that impede DNA and RNA synthesis. Many of them have a similar structure to the building blocks of DNA and RNA. The building blocks are [[nucleotide]]s; a molecule comprising a [[nucleobase]], a sugar and a [[phosphate group]]. The nucleobases are divided into [[purine]]s ([[guanine]] and [[adenine]]) and [[pyrimidine]]s ([[cytosine]], [[thymine]] and [[uracil]]). Anti-metabolites resemble either nucleobases or nucleosides (a nucleotide without the phosphate group), but have altered [[chemical group]]s.<ref name="pmid19476376">{{cite journal | vauthors = Parker WB | title = Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer | journal = Chemical Reviews | volume = 109 | issue = 7 | pages = 2880–93 | date = July 2009 | pmid = 19476376 | pmc = 2827868 | doi = 10.1021/cr900028p }}</ref> These drugs exert their effect by either blocking the enzymes required for DNA synthesis or becoming incorporated into DNA or RNA. By inhibiting the enzymes involved in DNA synthesis, they prevent mitosis because the DNA cannot duplicate itself. Also, after misincorporation of the molecules into DNA, [[DNA damage]] can occur and programmed cell death ([[apoptosis]]) is induced. Unlike alkylating agents, anti-metabolites are cell cycle dependent. This means that they only work during a specific part of the cell cycle, in this case [[S-phase]] (the DNA synthesis phase). For this reason, at a certain dose, the effect plateaus and proportionally no more cell death occurs with increased doses. Subtypes of the anti-metabolites are the [[antifolate|anti-folates]], fluoropyrimidines, deoxynucleoside analogues and [[thiopurine]]s.<ref name=lind /><ref name="pmid19476376" />

The anti-folates include [[methotrexate]] and [[pemetrexed]]. Methotrexate inhibits [[dihydrofolate reductase]] (DHFR), an enzyme that regenerates [[tetrahydrofolate]] from [[dihydrofolate]]. When the enzyme is inhibited by methotrexate, the cellular levels of folate coenzymes diminish. These are required for [[thymidylate]] and purine production, which are both essential for DNA synthesis and cell division.<ref name=Airley2009/>{{rp|55–59}}<ref name=Wood2005/>{{rp|11}} Pemetrexed is another anti-metabolite that affects purine and pyrimidine production, and therefore also inhibits DNA synthesis. It primarily inhibits the enzyme [[thymidylate synthase]], but also has effects on DHFR, aminoimidazole carboxamide ribonucleotide formyltransferase and [[glycinamide ribonucleotide formyltransferase]].<ref name="pmid15217974">{{cite journal | vauthors = Adjei AA | title = Pemetrexed (ALIMTA), a novel multitargeted antineoplastic agent | journal = Clinical Cancer Research | volume = 10 | issue = 12 Pt 2 | pages = 4276s–4280s | date = June 2004 | pmid = 15217974 | doi = 10.1158/1078-0432.CCR-040010 | s2cid = 31467685 }}</ref> The fluoropyrimidines include [[fluorouracil]] and [[capecitabine]]. Fluorouracil is a nucleobase analogue that is metabolised in cells to form at least two active products; 5-fluourouridine monophosphate (FUMP) and 5-fluoro-2'-deoxyuridine 5'-phosphate (fdUMP). FUMP becomes incorporated into RNA and fdUMP inhibits the enzyme thymidylate synthase; both of which lead to cell death.<ref name=Wood2005/>{{rp|11}} Capecitabine is a [[prodrug]] of 5-fluorouracil that is broken down in cells to produce the active drug.<ref name="pmid12515569">{{cite journal | vauthors = Wagstaff AJ, Ibbotson T, Goa KL | title = Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer | journal = Drugs | volume = 63 | issue = 2 | pages = 217–36 | year = 2003 | pmid = 12515569 | doi = 10.2165/00003495-200363020-00009 }}</ref> The deoxynucleoside analogues include [[cytarabine]], [[gemcitabine]], [[decitabine]], [[azacitidine]], [[fludarabine]], [[nelarabine]], [[cladribine]], [[clofarabine]], and [[pentostatin]]. The thiopurines include [[thioguanine]] and [[mercaptopurine]].<ref name=lind /><ref name="pmid19476376" />

==== 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>

==== Topoisomerase inhibitors ====
[[File:Topoisomerase Inhibitor.JPG|thumb|Topoisomerase I and II Inhibitors]]
{{Main|Topoisomerase inhibitor}}
Topoisomerase inhibitors are drugs that affect the activity of two enzymes: [[topoisomerase I]] and [[topoisomerase II]]. When the DNA double-strand helix is unwound, during DNA replication or [[transcription (biology)|transcription]], for example, the adjacent unopened DNA winds tighter (supercoils), like opening the middle of a twisted rope. The stress caused by this effect is in part aided by the topoisomerase enzymes. They produce single- or double-strand breaks into DNA, reducing the tension in the DNA strand. This allows the normal unwinding of DNA to occur during [[DNA replication|replication]] or transcription. Inhibition of topoisomerase I or II interferes with both of these processes.<ref>{{cite book |vauthors=Lodish H, Berk A, Zipursky SL |title=Molecular Cell Biology. 4th edition. The Role of Topoisomerases in DNA Replication|year=2000|publisher=New York: W. H. Freeman|url=https://www.ncbi.nlm.nih.gov/books/NBK21703/|display-authors=etal }}</ref><ref name="pmid12351817">{{cite journal | vauthors = Goodsell DS | title = The molecular perspective: DNA topoisomerases | journal = Stem Cells | volume = 20 | issue = 5 | pages = 470–1 | year = 2002 | pmid = 12351817 | doi = 10.1634/stemcells.20-5-470 | s2cid = 9257158 | doi-access = free }}</ref>

Two topoisomerase I inhibitors, [[irinotecan]] and [[topotecan]], are semi-synthetically derived from [[camptothecin]], which is obtained from the Chinese ornamental tree ''[[Camptotheca acuminata]]''.<ref name="pmid14508075" /> Drugs that target topoisomerase II can be divided into two groups. The topoisomerase II poisons cause increased levels enzymes bound to DNA. This prevents DNA replication and transcription, causes DNA strand breaks, and leads to programmed cell death ([[apoptosis]]). These agents include [[etoposide]], [[doxorubicin]], [[mitoxantrone]] and [[teniposide]]. The second group, catalytic inhibitors, are drugs that block the activity of topoisomerase II, and therefore prevent DNA synthesis and translation because the DNA cannot unwind properly. This group includes [[novobiocin]], merbarone, and [[aclarubicin]], which also have other significant mechanisms of action.<ref name="pmid19377506">{{cite journal | vauthors = Nitiss JL | title = Targeting DNA topoisomerase II in cancer chemotherapy | journal = Nature Reviews. Cancer | volume = 9 | issue = 5 | pages = 338–50 | date = May 2009 | pmid = 19377506 | pmc = 2748742 | doi = 10.1038/nrc2607 }}</ref>

==== Cytotoxic antibiotics ====
The cytotoxic [[antibiotic]]s are a varied group of drugs that have various mechanisms of action. The common theme that they share in their chemotherapy indication is that they interrupt [[cell division]]. The most important subgroup is the [[anthracycline]]s and the [[bleomycin]]s; other prominent examples include [[mitomycin C]] and [[actinomycin]].<ref name = "Offermanns_2008">{{cite book |url=https://books.google.com/books?id=iwwo5gx8aX8C&pg=PA155 |title=Encyclopedia of Molecular Pharmacology | vauthors = Offermanns S, Rosenthal W |date=2008-08-14 |publisher=Springer Science & Business Media |isbn=9783540389163 | page = 155 }}</ref>

Among the anthracyclines, [[doxorubicin]] and [[daunorubicin]] were the first, and were obtained from the [[bacterium]] ''[[Streptomyces peucetius]]''.<ref>{{Cite book |url=https://books.google.com/books?id=iwwo5gx8aX8C&pg=PA91 |title=Encyclopedia of Molecular Pharmacology | vauthors = Offermanns S, Rosenthal W  |date=2008-08-14 |publisher=Springer Science & Business Media |isbn=9783540389163 |pages=91ff }}</ref> Derivatives of these compounds include [[epirubicin]] and [[idarubicin]]. Other clinically used drugs in the anthracycline group are [[pirarubicin]], [[aclarubicin]], and [[mitoxantrone]].<ref>{{cite journal | pmid = 3048848| year = 1988| vauthors = Koeller J, Eble M | title = Mitoxantrone: A novel anthracycline derivative| journal = Clinical Pharmacy| volume = 7| issue = 8| pages = 574–81 }}</ref> The mechanisms of anthracyclines include [[DNA intercalation]] (molecules insert between the two strands of DNA), generation of highly reactive [[free radicals]] that damage intercellular molecules and topoisomerase inhibition.<ref name="pmid15169927">{{cite journal | vauthors = Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L | s2cid = 13138853 | title = Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity | journal = Pharmacological Reviews | volume = 56 | issue = 2 | pages = 185–229 | date = June 2004 | pmid = 15169927 | doi = 10.1124/pr.56.2.6 }}</ref>

Actinomycin is a complex molecule that intercalates DNA and prevents [[RNA synthesis]].<ref name="pmid2410919">{{cite journal | vauthors = Sobell HM | title = Actinomycin and DNA transcription | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 16 | pages = 5328–31 | date = August 1985 | pmid = 2410919 | pmc = 390561 | doi = 10.1073/pnas.82.16.5328 | bibcode = 1985PNAS...82.5328S | doi-access = free }}</ref>

Bleomycin, a [[glycopeptide]] isolated from ''[[Streptomyces verticillus]]'', also intercalates DNA, but produces [[free radical]]s that damage DNA. This occurs when bleomycin binds to a [[metal ion]], becomes [[reduction (chemistry)|chemically reduced]] and reacts with [[oxygen]].<ref name="pmid1384141">{{cite journal | vauthors = Dorr RT | title = Bleomycin pharmacology: mechanism of action and resistance, and clinical pharmacokinetics | journal = Seminars in Oncology | volume = 19 | issue = 2 Suppl 5 | pages = 3–8 | date = April 1992 | pmid = 1384141 }}</ref><ref name=Airley2009/>{{rp|87}}

Mitomycin is a cytotoxic antibiotic with the ability to alkylate DNA.<ref name="pmid2131038">{{cite journal | vauthors = Verweij J, Pinedo HM | title = Mitomycin C: mechanism of action, usefulness and limitations | journal = Anti-Cancer Drugs | volume = 1 | issue = 1 | pages = 5–13 | date = October 1990 | pmid = 2131038 | doi = 10.1097/00001813-199010000-00002 }}</ref>