Although your immune system is meant to be defending your body from attack, it could actually be the root cause of some cervical, head and neck cancers that are caused by human papillomavirus (HPV).
Scientists know that the majority of cancers are caused by external factors, such as UV radiation or smoking, which trigger DNA mutations in the body.
Now new research has been looking at the role of a specific family of enzymes, APOBEC3, which normally aid the body in fighting against infection by disabling the DNA of a virus, but can go rogue.
In the case of some cancers APOBEC3 can spill over from defensive mode into scrambling your own DNA, causing mutation and damage in the host genome that leads to cancer.
Pyeon said: “The APOBEC3 family can explain how some of these mutations are created. APOBEC3A can be activated in many ways ― not just with HPV infection ― and its action may drive a percentage of oncogenic mutations across many cancer types.”
In fact data obtained by the team showed signatures of APOBEC3-mediated mutations in the PIK3CA gene of about 40% of HPV-positive head and neck cancers.
But only 10% of HPV-negative head and neck cancers: “Our study shows that a significant fraction of mutations in HPV-positive cancers are potentially caused by one of these APOBEC3 enzymes,” said Pyeon.
Meaning that the enzyme does not successfully eliminate the HPV virus, which remains as a chronic infection.
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Not only that but HPV is able to evolve and adapt its genome against the APOBEC3, altering and reducing the target sequences, so the enzyme is unable to interrupt it’s behaviour.
Pyeon points out that because APOBEC3A is an enzyme, it would likely be susceptible to drug development aimed at stopping its action.
Instead they hope to teach tumor neoantigen-based immunotherapies to recognise these cells as well.
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