Editing Chemotherapy (section)

==== 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" />