The identification of genetic vulnerabilities in head and neck cancers for the development of novel therapies.

识别头颈癌的遗传脆弱性以开发新疗法。

• 批准号: MR/P013457/1
• 负责人: Ultan McDermott
• 金额: $ 50.97万
• 依托单位: Wellcome Sanger Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP013457%2F1
• 关键词: identification; genetic; vulnerabilities; head; neck

Every year ~370,000 of the world population will die of head and neck squamous cell carcinoma (HNSCC), and of these more than 80% will be from the Asian sub-continent. In Malaysia, HNSCC is the second commonest form of cancer. Less than 50% of HNSCC patients will survive beyond 5 years after diagnosis, largely due to a lack of effective therapies for this cancer. There is compelling evidence that identifying the genes that are responsible for the survival and growth of cancer cells can help us develop new drugs, and more importantly determine which existing drugs are most effective for specific patients. Here, using cancer cells that were derived from Asian HNSCC patients, we will use newly developed powerful gene editing techniques to identify critical genes that are responsible for cancer survival, and where inhibiting these would result in cancer cell death or growth arrest. The identification of genes that are essential for cancer cell survival will result in identification of relevant existing drugs that could be re-purposed for the treatment of HNSCC. This approach would shorten the drug development markedly as the safety and efficacy profiles of these would already be well-documented. In addition, the knowledge of the genes that drive HNSCC would afford an opportunity to develop novel drugs that could be effective in the treatment of HNSCC.

每年约有370，000世界人口将死于头颈部鳞状细胞癌（HNSCC），其中超过80%将来自亚洲次大陆。在马来西亚，HNSCC是第二常见的癌症。不到50%的HNSCC患者在诊断后存活超过5年，这主要是由于缺乏有效的治疗方法。有令人信服的证据表明，确定负责癌细胞生存和生长的基因可以帮助我们开发新药，更重要的是确定哪些现有药物对特定患者最有效。在这里，使用来自亚洲HNSCC患者的癌细胞，我们将使用新开发的强大的基因编辑技术来识别负责癌症存活的关键基因，以及抑制这些基因将导致癌细胞死亡或生长停滞的基因。对癌细胞存活所必需的基因的鉴定将导致鉴定出可以重新用于治疗HNSCC的相关现有药物。这种方法将显著缩短药物开发时间，因为这些药物的安全性和有效性已经有了很好的记录。此外，驱动HNSCC的基因的知识将为开发可能有效治疗HNSCC的新药提供机会。

项目成果

Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway.

口服鳞状细胞癌的全基因组CRISPR筛选显示河马途径中的适应性基因。

• DOI: 10.7554/elife.57761
• 发表时间: 2020-09-29
• 期刊: eLife
• 影响因子: 7.7
• 作者: Chai AWY;Yee PS;Price S;Yee SM;Lee HM;Tiong VK;Gonçalves E;Behan FM;Bateson J;Gilbert J;Tan AC;McDermott U;Garnett MJ;Cheong SC
• 通讯作者: Cheong SC