{"id":839,"date":"2020-08-26T09:31:58","date_gmt":"2020-08-26T09:31:58","guid":{"rendered":"https:\/\/clinlabint.3wstaging.nl\/cause-of-resistance-to-breakthrough-breast-and-ovarian-cancer-drug\/"},"modified":"2021-01-08T11:08:35","modified_gmt":"2021-01-08T11:08:35","slug":"cause-of-resistance-to-breakthrough-breast-and-ovarian-cancer-drug","status":"publish","type":"post","link":"https:\/\/clinlabint.com\/cause-of-resistance-to-breakthrough-breast-and-ovarian-cancer-drug\/","title":{"rendered":"Cause of resistance to breakthrough breast and ovarian cancer drug"},"content":{"rendered":"<p><span lang=\"EN-GB\">Scientists have identified a mutation that gives cancer cells resistance to the breakthrough cancer treatment olaparib and other PARP inhibitors.<\/span><br \/>\n<span lang=\"EN-GB\">The study findings could help predict which patients will develop resistance to PARP inhibitors and allow doctors to alter treatment at the earliest possible opportunity.<\/span><br \/>\n<span lang=\"EN-GB\">A team at The Institute of Cancer Research, London, used gene editing to identify a specific mutation in the PARP1 protein that prevents PARP inhibitors from working.<\/span><br \/>\n<span lang=\"EN-GB\">Testing for this mutation could add another level of personalisation to an already targeted treatment \u2013 helping guide decisions about whether to use PARP inhibitors in the first place, and when to switch to other drugs, such as platinum-based therapies.<\/span><br \/>\n<span lang=\"EN-GB\">PARP1 is crucial for the repair of damaged DNA and is an important target for olaparib and other PARP inhibitors. These drugs are especially effective in patients who already have weaknesses in DNA repair because of inherited errors in the BRCA genes \u2013 a discovery that was made at the ICR.<\/span><br \/>\n<span lang=\"EN-GB\">The scientists used new \u2018CRIPSR-Cas9\u2019 gene editing technology to generate mutations in small, targeted sections of the PARP1 gene, and tagged the mutant protein with a fluorescent protein so their effects could be tracked.<\/span><br \/>\n<span lang=\"EN-GB\">This approach allowed the researchers to observe the effect of specific mutations on PARP1 and on the sensitivity of cancer cells to PARP inhibitors, such as olaparib and talazoparib.<\/span><br \/>\n<span lang=\"EN-GB\">Olaparib is available on the NHS for women with ovarian cancer who have inherited BRCA mutations, and is currently being evaluated for breast cancer. It was the first ever cancer drug to be approved that is targeted against an inherited genetic fault.<\/span><br \/>\n<span lang=\"EN-GB\">The study identified specific PARP1 mutations which disrupt the ability of the protein to bind to DNA, which means PARP inhibitors can no longer trap them at the site of DNA damage.<\/span><br \/>\n<span lang=\"EN-GB\">The researchers found that, contrary to their original predictions, cancer cells with certain mutations in the BRCA1 gene could survive this loss of PARP1\u2019s DNA repair function \u2013 making them resistant to PARP inhibitors.<\/span><br \/>\n<span lang=\"EN-GB\">It is thought that in these cases the BRCA1 gene retains some function, providing some residual ability to repair DNA despite the loss of PARP1.<\/span><br \/>\n<span lang=\"EN-GB\">The scientists emphasised that further research needs to be carried out to examine more PARP1 mutations in patients as only one example in humans was found in this study.<\/span><br \/>\n<span lang=\"EN-GB\">The team is looking to apply this same gene editing approach to study how resistance arises to other drugs, and if it is possible to predict how quickly this resistance will progress.<\/span><\/p>\n<p>Institute of Cancer Research<link https:\/\/www.icr.ac.uk\/news-archive\/scientists-identify-cause-of-resistance-to-breakthrough-breast-and-ovarian-cancer-drug _blank external-link-new-window \"Opens external link in new window\"><span lang=\"EN-GB\">www.icr.ac.uk\/news-archive\/scientists-identify-cause-of-resistance-to-breakthrough-breast-and-ovarian-cancer-drug<\/span><\/link>\n","protected":false},"excerpt":{"rendered":"<p>Scientists have identified a mutation that gives cancer cells resistance to the breakthrough cancer treatment olaparib and other PARP inhibitors. The study findings could help predict which patients will develop resistance to PARP inhibitors and allow doctors to alter treatment at the earliest possible opportunity. A team at The Institute of Cancer Research, London, used [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/839"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=839"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/839\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=839"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=839"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=839"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}