{"id":1392,"date":"2019-12-31T02:39:08","date_gmt":"2019-12-31T07:39:08","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=1392"},"modified":"2020-02-17T02:59:28","modified_gmt":"2020-02-17T07:59:28","slug":"science-translational-medicine-synthetic-mrna-nanoparticle-mediated-restoration-of-p53-tumor-suppressor-sensitizes-p53-deficient-cancers-to-mtor-inhibition","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/science-translational-medicine-synthetic-mrna-nanoparticle-mediated-restoration-of-p53-tumor-suppressor-sensitizes-p53-deficient-cancers-to-mtor-inhibition\/","title":{"rendered":"Science Translational Medicine: Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to mTOR inhibition"},"content":{"rendered":"

In a new study, using advances in nanotechnology, researchers have found that restoring\u00a0p53<\/u><\/a>\u00a0not only delays the growth of p53-deficient liver and lung\u00a0cancer<\/u><\/a>\u00a0cells, but may also make cancer drugs mTOR inhibitors more sensitive.\u00a0The results were recently published in the journal Science Translational Medicine under the title Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to\u00a0<\/i><\/em>mTOR<\/i><\/u><\/em><\/a>\u00a0inhibition<\/i><\/em>.<\/p>\n

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Tumor suppressor gene p53, also known as the guardian of the genome, plays a vital role in cancer prevention.\u00a0Because of its powerful effect, it is one of the most commonly damaged genes in cancer. One of the reasons that cancer cells are so difficult to kill is that they often lack p53, a key tumor suppressor that promotes apoptosis. In preclinical trials, the researchers used synthetic mRNA nanoparticles to restore p53, making lung and liver cancer cells sensitive to existing cancer drugs.<\/p>\n

Scientists have long been looking for a way to restore the activity of tumor suppressor genes such as p53.\u00a0Recently, attention has turned to a method developed by Bregan Women\u2019s Hospital to deliver synthetic messenger RNA (mRNA) using nanotechnology.\u00a0Researchers found that restoring p53 not only delays the growth of p53-deficient liver and lung cancer cells but may also make tumors more sensitive to mTOR inhibitors.<\/p>\n

\u201cmTOR inhibitors have been approved for the treatment of certain types of cancer, but do not work well in clinical trials of many common cancers,\u201d said Dr. Jinjun Shi, \u201cThe evidence we provide in this new study suggests that the lipid-polymer hybrid mRNA nanoparticles platform we developed to restore p53 may make cancer cells sensitive to mTOR inhibitors.\u00a0This represents a potentially powerful combination of cancer treatment.\u201d<\/p>\n

The researchers used a platform of redox reactive nanoparticles to deliver synthetic mRNA that encodes p53.\u00a0This synthesis of p53 leads to cell cycle arrest and cell death, and delays the growth of liver and lung cancer cells where p53 has been removed.\u00a0In addition, this synthetic p53 makes these cancer cells more sensitive to everolimus, a mTOR inhibitor.\u00a0They reported successful results in a variety of in vitro and in vivo models.<\/p>\n

Previous Ivimus clinical trials have failed to show clinical benefits in patients with advanced liver cancer and lung cancer, but responses to the drug were shown to vary widely among current patients.\u00a0Existing studies have also found that p53 has changed in about 36% of hepatocellular carcinoma (the most common form of liver cancer) and 68% of non-small cell lung cancer.<\/p>\n

Further preclinical development and evaluation will be needed to explore the clinical transformational potential and scalability of this approach, as well as its applicability to other p53 mutations and other cancers, the researchers noted.\u00a0\u201cWe hope that this mRNA nanoparticles method can be applied to many other tumor suppressor genes and properly combined with other treatments to develop an effective combination therapy for cancer.\u201d<\/p>\n

 <\/p>\n

References<\/p>\n

Kong, N., Tao, W., Ling, X., Wang, J., Xiao, Y., Shi, S., … & Duda, D. G. (2019). Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to mTOR inhibition.\u00a0Science Translational Medicine<\/em>,\u00a011<\/em>(523).<\/p>\n","protected":false},"excerpt":{"rendered":"

In a new study, using advances in nanotechnology, researchers have found that restoring\u00a0p53\u00a0not only delays the growth of p53-deficient liver and lung\u00a0cancer\u00a0cells, but may also make cancer drugs mTOR inhibitors […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[16],"tags":[579,397,536,17],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/1392"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=1392"}],"version-history":[{"count":3,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/1392\/revisions"}],"predecessor-version":[{"id":1457,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/1392\/revisions\/1457"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=1392"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=1392"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=1392"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}