Molecular profiling of sarcomas to enable clinical prediction and elucidate molecular pathogenesis

肉瘤是影响年轻人的罕见癌症，死亡率为50%。治疗涉及专家的多学科方法，即使有效，也往往会导致生活质量的长期损失。大多数肉瘤是用放疗和手术相结合的方法治疗的，与单独手术相比，这显著提高了生存率。放射治疗并不能帮助所有患者，有副作用，而且昂贵和耗时。如果能够识别出不能从放疗中获益的患者，最大限度地减少治疗带来的不必要伤害，并提供替代的更有效的治疗方法，这将是非常有用的。不幸的是，我们还不能区分哪些肿瘤会有反应，哪些不会。此外，人们对肉瘤的潜在原因知之甚少。该项目有两个目标：第一，通过针对那些无法从标准治疗中获益的患者，使我们目前的治疗更有效;第二，更好地了解肉瘤的病因，以便开发更好的治疗方法。微阵列能够同时研究数千个基因，当它们结合在一起时，就形成了每个肿瘤的独特画像。我们的单位，在澳大利亚最大的肉瘤服务之一，有机会获得大量的肿瘤样本，与优秀的基础科学支持。现在可以问什么是对放射治疗有反应的肉瘤的分子“肖像”，使用可以在治疗开始前获得的微量肿瘤材料。我们还希望通过发现其失活对这种癌症的发展至关重要的关键基因来确定肉瘤的分子基础。这样的基因可以形成靶向治疗的基础。这种方法将为未来的肉瘤研究奠定坚实的基础，并有可能减少不必要的成本和痛苦的患者经历的治疗，这是不可能是有效的。

Sarcomas are uncommon cancers which affect the young, with a 50% mortality. Treatment involves an expert multidisciplinary approach, and even when effective often entails long-term loss of quality of life. Most sarcomas are treated with a combination of radiotherapy and surgery, which improves survival significantly compared to surgery alone. Radiotherapy does not help all patients, has side-effects and is expensive and time consuming. It would be useful to be able to identify patients who will not benefit from radiotherapy, to minimise unnecessary harm from treatment and offer alternate more effective therapies. Unfortunately, we cannot yet distinguish which tumours will respond and which will not. Moreover, the uderlying causes of sarcoma are poorly understood. This project has two aims: first to make our current therapies more effective by targeting those who will not benefit from standard treatment; and second to better understand the causes of sarcoma, in order to develop better treatment. Microarrays enable the simultaneous study of thousands of genes, which when combined form a unique portrait of each tumour. Our unit, one of the largest sarcoma sevices in Australia, has access to large numbers of tumour samples, with excellent basic science support. It is now possible to ask what the molecular 'portrait' is of sarcomas which are responsive to radiotherapy, using tiny amounts of tumour material which can be obtained before treatment starts. We also hope to identify the molecular basis of sarcomas by finding the key genes whose inactivation is central to the development of this form of cancer. Such genes can then form the basis of targeted therapy. This approach will lay a solid foundation for future research into sarcomas, and has the potential to reduce unnecessary cost and suffering patients experience from treatments which are unlikely to be effective.