Editing Cancer (section)

=== Genetics ===
{{Main|Oncogenomics}}
[[File:Cancer requires multiple mutations from NIHen.png|thumb|upright|Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.]]
Cancer is fundamentally a disease of tissue growth regulation. For a normal cell to [[malignant transformation|transform]] into a cancer cell, the [[gene]]s that regulate cell growth and differentiation must be altered.<ref name="pmid18234754">{{cite journal |vauthors=Croce CM |s2cid=8813076 |title=Oncogenes and cancer |journal=The New England Journal of Medicine |volume=358 |issue=5 |pages=502–11 |date=January 2008 |pmid=18234754 |doi=10.1056/NEJMra072367}}</ref>

The affected genes are divided into two broad categories. [[Oncogene]]s are genes that promote cell growth and reproduction. [[Tumor suppressor gene]]s are genes that inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.<ref name="pmid11905807">{{cite journal |vauthors=Knudson AG |s2cid=20201610 |title=Two genetic hits (more or less) to cancer |journal=Nature Reviews. Cancer |volume=1 |issue=2 |pages=157–62 |date=November 2001 |pmid=11905807 |doi=10.1038/35101031}}</ref>

Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire [[chromosome]] can occur through errors in [[mitosis]]. More common are [[mutation]]s, which are changes in the [[nucleotide]] sequence of genomic DNA.

Large-scale mutations involve the deletion or gain of a portion of a chromosome. [[Gene duplication|Genomic amplification]] occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. [[Chromosomal translocation|Translocation]] occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the [[Philadelphia chromosome]], or translocation of chromosomes 9 and 22, which occurs in [[chronic myelogenous leukemia]] and results in production of the [[BCR (gene)|BCR]]-[[aBL (gene)|abl]] [[fusion protein]], an oncogenic [[tyrosine kinase]].

Small-scale mutations include point mutations, deletions, and insertions, which may occur in the [[promoter (genetics)|promoter]] region of a gene and affect its [[gene expression|expression]], or may occur in the gene's [[coding sequence]] and alter the function or stability of its [[protein]] product. Disruption of a single gene may also result from [[provirus|integration of genomic material]] from a [[DNA virus]] or [[retrovirus]], leading to the expression of ''viral'' oncogenes in the affected cell and its descendants.

Replication of the data contained within the DNA of living cells will [[probability|probabilistically]] result in some errors (mutations). Complex error correction and prevention are built into the process and safeguard the cell against cancer. If a significant error occurs, the damaged cell can self-destruct through programmed cell death, termed [[apoptosis]]. If the error control processes fail, then the mutations will survive and be passed along to [[cell division|daughter cells]].

Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called [[carcinogen]]s, repeated physical injury, heat, ionising radiation, or [[hypoxia (medical)|hypoxia]].<ref>{{cite journal |vauthors=Nelson DA, Tan TT, Rabson AB, Anderson D, Degenhardt K, White E |title=Hypoxia and defective apoptosis drive genomic instability and tumorigenesis |journal=Genes & Development |volume=18 |issue=17 |pages=2095–107 |date=September 2004 |pmid=15314031 |pmc=515288 |doi=10.1101/gad.1204904}}</ref>

The errors that cause cancer are self-amplifying and compounding, for example:
* A mutation in the error-correcting machinery of a cell might cause that cell and its children to accumulate errors more rapidly.
* A further mutation in an oncogene might cause the cell to reproduce more rapidly and more frequently than its normal counterparts.
* A further mutation may cause the loss of a tumor suppressor gene, disrupting the apoptosis signaling pathway and immortalizing the cell.
* A further mutation in the signaling machinery of the cell might send error-causing signals to nearby cells.

The transformation of a normal cell into cancer is akin to a [[chain reaction]] caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape more controls that limit normal tissue growth. This rebellion-like scenario is an undesirable [[survival of the fittest]], where the driving forces of [[evolution]] work against the body's design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed ''[[Somatic evolution in cancer|clonal evolution]]'', drives progression towards more invasive [[cancer staging|stages]].<ref name="pmid17109012">{{cite journal |vauthors=Merlo LM, Pepper JW, Reid BJ, Maley CC |s2cid=8040576 |title=Cancer as an evolutionary and ecological process |journal=Nature Reviews. Cancer |volume=6 |issue=12 |pages=924–35 |date=December 2006 |pmid=17109012 |doi=10.1038/nrc2013}}</ref> Clonal evolution leads to intra-[[tumour heterogeneity]] (cancer cells with heterogeneous mutations) that complicates designing effective treatment strategies and requires an [[Evolutionary therapy|evolutionary approach to designing treatment]].

Characteristic abilities developed by cancers are divided into categories, specifically evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, metastasis, reprogramming of energy metabolism and evasion of immune destruction.<ref name=Han2000/><ref name=Han2011/>