文章：

肉瘤发生的机制

Mechanisms of sarcoma development

原文发布日期：2003-09-01

DOI: 10.1038/nrc1168

类型: Review Article

开放获取: 否

要点：

1. Sarcomas are a diverse group of relatively rare malignancies that are derived from bone, muscle, cartilage and other connective tissues.
2. Genetically, sarcomas fall into two main categories. One group of sarcomas is characterized by a tumour-specific translocation that seems to be central to the pathogenesis of the tumour, and indeed is being incorporated as diagnostic criteria. Another group of sarcomas are characterized not by a recurring, tumour-specific genetic alteration but by complex karyotypes that are characteristic of severe genetic and chromosomal instability.
3. Most sarcomas have abnormalities in the RB, p53 and/or specific growth-factor signalling pathways. In several specific sarcoma types, specific genetic alterations lead to activation of specific tyrosine kinase growth-factor receptors, and these have been successfully treated with drugs that specifically inhibit the activated kinase receptor.
4. Therapeutic interventions that are aimed at inhibiting these activated pathways have already shown activity in the treatment of specific sarcomas. It is likely that further evolution of the classification of these tumours based on biological properties, in addition to histological classifications, will allow for more specific therapeutic interventions.
5. It has been relatively difficult to develop genetic animal models of translocation-specific sarcomas, and work is ongoing to do so. There are several mouse models of sarcomas that do not harbour tumour-specific translocations.
6. In the future, therapy for sarcomas is likely to involve use of agents that specifically target activated growth-factor signalling pathways — often in combination with standard cytoreductive chemotherapy and surgery. It is likely that this approach will convert an acute, often lethal disease to a chronic, non-debilitating one.

要点翻译：

1. 肉瘤是一组相对罕见的恶性肿瘤，起源于骨、肌肉、软骨及其他结缔组织，具有高度异质性。
2. 从遗传学角度，肉瘤主要分为两大类：一类以肿瘤特异性易位为特征，这种易位在肿瘤发病机制中起核心作用，并已被纳入诊断标准；另一类则缺乏反复出现的特异性基因改变，但具有复杂的核型特征，表现为严重的遗传及染色体不稳定性。
3. 大多数肉瘤存在RB、p53基因和/或特定生长因子信号通路的异常。在某些特定肉瘤类型中，特异性遗传改变导致酪氨酸激酶生长因子受体激活，而针对这些激活激酶受体的抑制剂药物已成功应用于治疗。
4. 针对这些激活通路的靶向治疗已在特定肉瘤治疗中显现疗效。未来，结合组织学分类与生物学特性进一步优化肿瘤分类体系，将有助于实现更精准的治疗干预。
5. 目前构建易位特异性肉瘤的遗传动物模型仍存在困难，相关研究仍在推进。已有若干小鼠模型可模拟非易位相关肉瘤的发展。
6. 展望未来，肉瘤治疗很可能将聚焦于靶向抑制激活的生长因子信号通路药物——通常联合常规细胞减灭化疗与手术。这种策略有望将这一急性致死性疾病转化为可控的慢性非衰弱性疾病。

英文摘要：

Sarcomas are a rare and diverse group of tumours that are derived from connective tissues, including bone, muscle and cartilage. Although there are instances of hereditary predisposition to sarcomas, the overwhelming majority of such tumours are sporadic. In the past decade, we have gained much insight into the genetic abnormalities that seem to underlie the pathogenesis of these tumours. This information has already led to new classification of many sarcomas, as well as to successful therapies that are targeted at specific genetic abnormalities. It is likely that this approach will lead to continued refinements in classification and treatment of these tumours.

摘要翻译： 

肉瘤是一类罕见且异质性强的肿瘤，起源于骨、肌肉、软骨等结缔组织。尽管存在少数遗传性易感病例，但绝大多数肉瘤为散发性。过去十年，我们对其发病机制相关的遗传异常有了深入了解，这些发现已促使许多肉瘤被重新分类，并推动了针对特定遗传异常的靶向治疗成功应用于临床。这一策略有望在未来进一步优化肉瘤的分类与治疗。

原文链接：

Mechanisms of sarcoma development