IMPROVING RADIOIODINE TREATMENT OF THYROID AND OTHER TUMOURS

改善甲状腺和其他肿瘤的放射性碘治疗

• 批准号: MR/J001414/1
• 负责人: Christopher McCabe
• 金额: $ 69.5万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ001414%2F1
• 关键词: IMPROVING; RADIOIODINE; TREATMENT; THYROID; OTHER

A main treatment option for thyroid cancer, and a potential therapeutic strategy in breast and prostate cancer, is radioactive iodide, which is concentrated in the cell, and then kills cancer cells. One problem with this is that the protein NIS which helps cells take up the radioactive iodide is not as active in cancer cells as it is in normal cells. This means that the treatment is not as effective as it could be. We are aiming to change this. We have discovered that a protein called PBF drastically reduces the ability of NIS to function. We therefore want to explore how we can overcome this effect, particularly because thyroid cancers have high levels of PBF, and breast and prostate cancers can be engineered to express functional levels of NIS. If we can prevent PBF from reducing NIS activity, we may restore radioactive iodide uptake. This should directly improve therapy and outcome, particularly for the subset of patients who are currently very difficult to treat, and who have less than a 50% chance of surviving 5 years with thyroid cancer. Also, given that PBF is highly expressed in other cancers, changing the way that PBF affects NIS would have further potential in the treatment of breast and prostate cancers.

甲状腺癌的一种主要治疗方法，以及乳腺癌和前列腺癌的一种潜在治疗策略，是放射性碘化物，它集中在细胞内，然后杀死癌细胞。其中一个问题是，帮助细胞吸收放射性碘的蛋白质NIS在癌细胞中不像在正常细胞中那么活跃。这意味着治疗并没有达到应有的效果。我们的目标是改变这一点。我们发现一种叫做PBF的蛋白质会大大降低NIS的功能。因此，我们想探索如何克服这种影响，特别是因为甲状腺癌有高水平的PBF，乳腺癌和前列腺癌可以被改造成表达功能水平的NIS。如果我们能阻止PBF降低NIS活性，我们就可以恢复放射性碘的吸收。这将直接改善治疗和结果，特别是对于目前很难治疗的患者，以及甲状腺癌患者5年生存率低于50%的患者。此外，鉴于PBF在其他癌症中高度表达，改变PBF影响NIS的方式将在乳腺癌和前列腺癌的治疗中具有进一步的潜力。

项目成果

Functional consequences of the first reported mutations of the proto-oncogene PTTG1IP/PBF.

• DOI: 10.1530/erc-16-0340
• 发表时间: 2017-09
• 期刊: Endocrine-related cancer
• 影响因子: 3.9
• 作者: Imruetaicharoenchoke W;Fletcher A;Lu W;Watkins RJ;Modasia B;Poole VL;Nieto HR;Thompson RJ;Boelaert K;Read ML;Smith VE;McCabe CJ
• 通讯作者: McCabe CJ

Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage response genes in thyroid cancer.

• DOI: 10.1038/onc.2017.154
• 发表时间: 2017-09-14
• 期刊: Oncogene
• 影响因子: 8
• 作者: Read ML;Fong JC;Modasia B;Fletcher A;Imruetaicharoenchoke W;Thompson RJ;Nieto H;Reynolds JJ;Bacon A;Mallick U;Hackshaw A;Watkinson JC;Boelaert K;Turnell AS;Smith VE;McCabe CJ
• 通讯作者: McCabe CJ

WOMEN IN CANCER PROFILE: From bedside to bench and back: my journey in thyroid disease.

女性癌症概况：从床边到工作台再回来：我的甲状腺疾病之旅。

• DOI: 10.1530/erc-16-0396
• 发表时间: 2016
• 期刊: Endocrine-related cancer
• 影响因子: 3.9
• 作者: Boelaert K