Editing Apoptosis (section)

===Defective pathways===
The many different types of apoptotic pathways contain a multitude of different biochemical components, many of them not yet understood.<ref name="pathogenesis">{{cite journal | vauthors = Thompson CB | title = Apoptosis in the pathogenesis and treatment of disease | journal = Science | volume = 267 | issue = 5203 | pages = 1456–1462 | date = March 1995 | pmid = 7878464 | doi = 10.1126/science.7878464 | s2cid = 12991980 | bibcode = 1995Sci...267.1456T }}</ref> As a pathway is more or less sequential in nature, removing or modifying one component leads to an effect in another. In a living organism, this can have disastrous effects, often in the form of disease or disorder. A discussion of every disease caused by modification of the various apoptotic pathways would be impractical, but the concept overlying each one is the same: The normal functioning of the pathway has been disrupted in such a way as to impair the ability of the cell to undergo normal apoptosis. This results in a cell that lives past its "use-by date" and is able to replicate and pass on any faulty machinery to its progeny, increasing the likelihood of the cell's becoming cancerous or diseased.{{citation needed|date=November 2024}}

A recently described example of this concept in action can be seen in the development of a lung cancer called [[NCI-H460]].<ref name="h460">{{cite journal | vauthors = Yang L, Mashima T, Sato S, Mochizuki M, Sakamoto H, Yamori T, Oh-Hara T, Tsuruo T | display-authors = 6 | title = Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide | journal = Cancer Research | volume = 63 | issue = 4 | pages = 831–837 | date = February 2003 | pmid = 12591734 | url = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12591734 | access-date = 2008-09-04 | archive-date = 2012-12-20 | archive-url = https://archive.today/20121220182836/http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12591734 | url-status = live }}</ref> The ''X-linked inhibitor of apoptosis protein'' ([[XIAP]]) is [[Gene expression|overexpressed]] in cells of the H460 [[cell line]]. XIAPs bind to the processed form of caspase-9 and suppress the activity of apoptotic activator [[cytochrome c]], therefore overexpression leads to a decrease in the number of proapoptotic agonists. As a consequence, the balance of anti-apoptotic and proapoptotic effectors is upset in favour of the former, and the damaged cells continue to replicate despite being directed to die. Defects in regulation of apoptosis in cancer cells occur often at the level of control of transcription factors. As a particular example, defects in molecules that control transcription factor NF-κB in cancer change the mode of transcriptional regulation and the response to apoptotic signals, to curtail dependence on the tissue that the cell belongs. This degree of independence from external survival signals, can enable cancer metastasis.<ref>{{cite journal | vauthors = Vlahopoulos SA | title = Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode | journal = Cancer Biology & Medicine | volume = 14 | issue = 3 | pages = 254–270 | date = August 2017 | pmid = 28884042 | pmc = 5570602 | doi = 10.20892/j.issn.2095-3941.2017.0029 }}</ref>

====Dysregulation of p53====
The tumor-suppressor protein [[p53]] accumulates when DNA is damaged due to a chain of biochemical factors. Part of this pathway includes alpha-[[interferon]] and beta-interferon, which induce transcription of the ''p53'' gene, resulting in the increase of p53 protein level and enhancement of cancer cell-apoptosis.<ref name="takaoka">{{cite journal | vauthors = Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T | display-authors = 6 | title = Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence | journal = Nature | volume = 424 | issue = 6948 | pages = 516–523 | date = July 2003 | pmid = 12872134 | doi = 10.1038/nature01850 | doi-access = free | bibcode = 2003Natur.424..516T }}</ref> p53 prevents the cell from replicating by stopping the [[cell cycle]] at G1, or interphase, to give the cell time to repair; however, it will induce apoptosis if damage is extensive and repair efforts fail.<ref name="pmid12052432">{{cite journal | vauthors = Bernstein C, Bernstein H, Payne CM, Garewal H | title = DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis | journal = Mutation Research | volume = 511 | issue = 2 | pages = 145–178 | date = June 2002 | pmid = 12052432 | doi = 10.1016/S1383-5742(02)00009-1 | bibcode = 2002MRRMR.511..145B }}</ref> Any disruption to the regulation of the ''p53'' or interferon genes will result in impaired apoptosis and the possible formation of tumors.<ref>{{Cite journal |last=Soussi |first=Thierry |date=2000 |title=The p53 Tumor Suppressor Gene: From Molecular Biology to Clinical Investigation |url=https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2000.tb06705.x |journal=Annals of the New York Academy of Sciences |language=en |volume=910 |issue=1 |pages=121–139 |doi=10.1111/j.1749-6632.2000.tb06705.x |pmid=10911910 |bibcode=2000NYASA.910..121S |issn=1749-6632}}</ref>