MICA: Stratification in COloRectal cancer: from biology to Treatment prediction: S-CORT

MICA：结肠直肠癌的分层：从生物学到治疗预测：S-CORT

• 批准号: MR/M016587/1
• 负责人: TIMOTHY MAUGHAN
• 金额: $ 647.25万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM016587%2F1
• 关键词: MICA; Stratification; COloRectal; cancer; biology

Colorectal cancer (CRC) is the 3rd most common cancer in the UK, with >40,000 new cases in 2011. While there have been improvements in CRC treatment, it remains a significant killer, with 16,000 deaths in 2011. Research by ourselves/others has revealed that a "one size fits all approach" will not work, as genetic changes in their CRC cells can cause treatments to fail in particular patients. This increased understanding has given rise to the concept of "stratified medicine", where testing a patient's sample prior to treatment can indicate which therapy works in this particular patient. This "stratified" approach also allows patients who will not respond to be spared the often toxic side effects. Recognising the need to provide treatments leading to better survival/Quality of Life (Qol), a group of researchers, clinicians, patient groups and industry have formed a consortium (S-CORT), harnessing its members expertise to develop new approaches to stratify patients to improve outcomes, thus delivering real benefit for CRC patients.S-CORTs objectives are to:1. Create a consortium united in the common goal to employ stratified medicine to yield better survival and QoL for CRC patients2. Build on discoveries by S-CORT researchers to identify particular stratification approaches for patients receiving different therapies for CRC. Three priorities have been establisheda. While the drug Oxaliplatin has increased our options for treating CRC, approximately 50% of patients don't respond and develop side effects that can affect their nervous system and reduce their QoL. Being able to decide in advance which patients respond, allows those patients to receive the drug while sparing non-responders the toxic side effectsb. ChemoRadiotherapy (CRT) is used in the treatment of rectal cancer, but 40% of patients with locally advanced disease gain no benefit. A stratification approach may not only indicate which patients to treat, but also allow design of new approaches to make RT more effectivec. In early disease, some patients can have aggressive cancer which invades other parts of the body. Identifying these patients in advance of treatment would allow them to receive more extensive surgery/RT while those with less aggressive disease can be treated with local rectal preserving treatment3. Establish a more complete understanding of the precise changes that occur in the genes and proteins of CRC cells and use this information to provide novel therapies for patients4. Develop our best candidates into clinical tests that select patients for the therapies that have the greatest chance of success and/or with the fewest side effects in their particular disease5. Bring together all our research into a database that will be a vital resource for future research, within and outside this consortium6. Ensure that the patient is at the centre of all activities in S-CORT, helping with the design of studies, participating in focus groups, meetings and conferences and contributing to the communication of the activities of S-CORT to healthcare and research professionals, patient groups and the public at large7. Publish our research findings in the best scientific journals and present our results at national and international conferences, thus demonstrating the quality of S-CORT's research 8. Examine how tests that we are developing will perform in the hospital for CRC patients and evaluate the health, economic and societal benefits of this approach 9. Ensure S-CORT's long term sustainability, thus driving implementation of new stratification approaches for CRC patients over the next decade, both in the UK and globallyDelivering these ambitious objectives will allow development of new clinical tests to predict success/ failure of new therapies which, coupled with our increased knowledge of CRC biology will drive a new treatment vision where stratified medicine approaches can significantly benefit our patients.

结直肠癌(CRC)是英国第三大常见癌症，2011年新增病例4万例。虽然结直肠癌的治疗有所改善，但它仍然是一个重要的杀手，2011年有16,000人死亡。我们/他人的研究表明，“一刀切”的方法不会奏效，因为他们的CRC细胞中的基因变化可能会导致特定患者的治疗失败。这种日益增长的认识催生了“分层医学”的概念，即在治疗前检测患者的样本可以表明哪种治疗方法对这个特定的患者有效。这种“分层”的方法还可以让那些没有反应的患者避免经常出现的毒副作用。认识到提供更好的生存/生活质量(QOL)治疗的必要性，一组研究人员、临床医生、患者团体和产业界组成了一个联盟(S-CORT)，利用其成员的专业知识开发新的方法来对患者进行分层，以改善结果，从而为结直肠癌患者带来真正的好处。S-CORT的目标是：1.创建一个团结在共同目标上的联盟，使用分层医学为结直肠癌患者提供更好的生存和生活质量2。以S-科特研究人员的发现为基础，为接受不同治疗方法的结直肠癌患者确定特定的分层方法。已经确定了三个优先事项。虽然药物奥沙利铂增加了我们治疗结直肠癌的选择，但大约50%的患者没有反应，并产生副作用，可能会影响他们的神经系统，降低他们的生活质量。能够提前决定哪些患者有反应，允许这些患者接受药物治疗，同时避免无反应者的毒副作用b。化疗放射治疗(CRT)用于直肠癌的治疗，但40%的局部晚期疾病患者没有受益。分层方法不仅可以指示要治疗哪些患者，还可以设计新的方法以使放射治疗更有效。在早期疾病中，一些患者可能患有侵袭身体其他部位的侵袭性癌症。在治疗前发现这些患者将使他们能够接受更广泛的手术/放疗，而那些侵袭性较小的患者可以进行局部直肠保留治疗。建立对结直肠癌细胞基因和蛋白质发生的精确变化的更全面的理解，并利用这些信息为患者提供新的治疗方法。将我们最好的候选者培养成临床测试，为在特定疾病中有最大成功机会和/或副作用最少的治疗选择患者。将我们所有的研究汇集到一个数据库中，该数据库将成为该联盟内外未来研究的重要资源。确保患者是S-CORT所有活动的中心，帮助设计研究，参加焦点小组、会议和会议，并促进S-CORT的活动与医疗保健和研究专业人员、患者群体和广大公众的沟通。在最好的科学期刊上发表我们的研究成果，并在国内和国际会议上展示我们的研究结果，从而展示S-科尔特的研究质量8.检查我们正在开发的测试将如何在医院对结直肠癌患者进行测试，并评估这种方法的健康、经济和社会效益9.确保S-科特的长期可持续性，从而推动未来十年在英国和全球对结直肠癌患者实施新的分层方法实现这些雄心勃勃的目标将允许开发新的临床测试来预测新疗法的成败，再加上我们对结直肠癌生物学知识的增加，将推动一种新的治疗愿景，在这种情况下，分层医学方法可以使我们的患者显著受益。

项目成果

Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer.

• DOI: 10.1073/pnas.2011411118
• 发表时间: 2021-09-28
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Andrijes R;Hejmadi RK;Pugh M;Rajesh S;Novitskaya V;Ibrahim M;Overduin M;Tselepis C;Middleton GW;Győrffy B;Beggs AD;Berditchevski F
• 通讯作者: Berditchevski F

HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial

• DOI: 10.1093/jnci/djz231
• 发表时间: 2020-09-01
• 期刊: JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
• 影响因子: 10.3
• 作者: Barber, Paul R.;Weitsman, Gregory;Ng, Tony
• 通讯作者: Ng, Tony

Molecular Subtyping Resource: a user-friendly tool for rapid biological discovery from transcriptional data.

• DOI: 10.1242/dmm.049257
• 发表时间: 2022-03-01
• 期刊: Disease models & mechanisms
• 影响因子: 4.3
• 作者: Ahmaderaghi B;Amirkhah R;Jackson J;Lannagan TRM;Gilroy K;Malla SB;Redmond KL;Quinn G;McDade SS;ACRCelerate Consortium;Maughan T;Leedham S;Campbell ASD;Sansom OJ;Lawler M;Dunne PD
• 通讯作者: Dunne PD

Prospective patient stratification into robust cancer-cell intrinsic subtypes from colorectal cancer biopsies.

• DOI: 10.1002/path.5051
• 发表时间: 2018-05
• 期刊: The Journal of pathology
• 作者: Alderdice M;Richman SD;Gollins S;Stewart JP;Hurt C;Adams R;McCorry AM;Roddy AC;Vimalachandran D;Isella C;Medico E;Maughan T;McArt DG;Lawler M;Dunne PD
• 通讯作者: Dunne PD

Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution.

• DOI: 10.1038/s41467-017-02295-5
• 发表时间: 2017-12-08
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Baker AM;Huang W;Wang XM;Jansen M;Ma XJ;Kim J;Anderson CM;Wu X;Pan L;Su N;Luo Y;Domingo E;Heide T;Sottoriva A;Lewis A;Beggs AD;Wright NA;Rodriguez-Justo M;Park E;Tomlinson I;Graham TA
• 通讯作者: Graham TA