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

结直肠癌（CRC）是英国第三大最常见的癌症，2011年新发病例达40万例。虽然结直肠癌的治疗已经有所改善，但它仍然是一个重要的杀手，2011年有16,000人死亡。我们和其他人的研究表明，“一刀切”的方法是行不通的，因为CRC细胞的基因变化可能导致特定患者的治疗失败。这种认识的增加产生了“分层医学”的概念，即在治疗前对患者的样本进行测试，可以表明哪种治疗方法对该特定患者有效。这种“分层”的方法也可以让那些对药物没有反应的患者免受毒副作用的影响。认识到需要提供更好的生存/生活质量（Qol）的治疗方法，一组研究人员，临床医生，患者团体和行业组成了一个联盟（S-CORT），利用其成员的专业知识开发新的方法来分层患者以改善结果，从而为结直肠癌患者带来真正的好处。S-CORTs的目标是：1。创建一个以共同目标联合起来的联盟，采用分层药物提高结直肠癌患者的生存率和生活质量2。以S-CORT研究人员的发现为基础，为接受不同CRC治疗的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，并产生影响神经系统和降低生活质量的副作用。能够提前决定哪些患者有反应，使这些患者接受药物治疗，同时使无反应者免受毒副作用。化疗（CRT）用于直肠癌的治疗，但40%的局部晚期患者没有获益。分层方法不仅可以指示治疗哪些患者，还可以设计新的方法使RT更有效。在早期疾病中，一些患者可能会有侵袭性癌症，并侵入身体的其他部位。在治疗前识别这些患者将允许他们接受更广泛的手术/RT，而那些疾病侵袭性较小的患者可以接受局部直肠保留治疗3。建立对CRC细胞中基因和蛋白质发生的精确变化的更完整的理解，并利用这些信息为患者提供新的治疗方法4。将我们最好的候选药物发展到临床试验中，选择对病人的特定疾病有最大成功机会和/或副作用最小的治疗方法。将我们所有的研究成果汇集到一个数据库中，这将是该联盟内外未来研究的重要资源。确保患者处于S-CORT所有活动的中心，帮助设计研究，参与焦点小组，会议和会议，并促进S-CORT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7。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成果，从而展示S-CORT的研究质量。检查我们正在开发的测试将如何在医院为CRC患者执行，并评估这种方法的健康，经济和社会效益。确保S-CORT的长期可持续性，从而推动未来十年在英国和全球范围内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试验来预测新疗法的成功/失败，再加上我们对结直肠癌生物学知识的增加，将推动新的治疗愿景，分层医学方法可以显著造福我们的患者。

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.