摘要
在西方国家中,结肠直肠癌(CRC)是引起癌死亡的第二大原因,且多数是由转移直肠癌导致。了解转移性结肠直肠癌(mCRC)病人的自然史和预后因素对临床试验的优化设计是必不可少的。目前应用于临床实践的主要预后因素与肿瘤行为(如:白细胞计数、乳酸脱氢酶水平、碱性磷酸酶水平),疾病程度(如肝外扩散的存在、受到影响的器官的数目)和全身性机能状态(如:东部合作肿瘤小组鉴定的体能状态)。然而,这些参数还不足以建立合适的治疗方案。mCRC的一线治疗方案是常规化疗方案(CHT) (如 FOLFOX, FOLFIRI, CAPOX)联合靶向特殊信号通路的药物制剂(TA)(如KRAS/NRAS WT 病例的帕尼单抗和西妥普单抗以及贝伐单抗)。虽然这种联合治疗方案的反应率超过50%,但是疾病的恶化仍然普遍,2年内只有少于10%的病人痊愈。目前二线和三线治疗的临床试验包括新的TA,如酪氨酸激酶受体抑制剂(蛋氨酸、人类表皮生长因子受体、胰岛素样生长因子1R),BRAF、MEK、PI3K、AKT、 mTORC、 NOTCH 和JAK1/JAK2酶抑制剂, 免疫疗法调节器和检查点抑制剂 (抗PD-L1 和 抗PD1)。尽管鉴定了多种预后和预测性生物标志物和特征,但是CHT和/或TA调节的这些生物标志物如何表达仍然不清楚,进而潜在的影响治疗反应。本文中,我们分析了mCRC预处理病人的一些肿瘤细胞和微环境如何影响新TA和免疫治疗策略的反应。
关键词: 生物标志物,结肠直肠的,上皮的,间叶细胞的,预后,抵抗力
图形摘要
Current Cancer Drug Targets
Title:Prognostic and Predictive Biomarkers in Colorectal Cancer. From the Preclinical Setting to Clinical Practice
Volume: 15 Issue: 8
Author(s): Joan Maurel and Antonio Postigo
Affiliation:
关键词: 生物标志物,结肠直肠的,上皮的,间叶细胞的,预后,抵抗力
摘要: Colorectal cancer (CRC) is the second largest cause of cancer mortality in Western countries, mostly due to metastasis. Understanding the natural history and prognostic factors in patients with metastatic CRC (mCRC) is essential for the optimal design of clinical trials. The main prognostic factors currently used in clinical practice are related to tumor behavior (e.g., white blood counts, levels of lactate dehydrogenase, levels of alkaline phosphatase) disease extension (e.g., presence of extrahepatic spread, number of organs affected) and general functional status (e.g., performance status as defined by the Eastern Cooperative Oncology Group). However, these parameters are not always sufficient to establish appropriate therapeutic strategies. First-line therapy in mCRC combines conventional chemotherapy (CHT) (e.g., FOLFOX, FOLFIRI, CAPOX) with a number of agents targeted to specific signaling pathways (TA) (e.g., panitumumab and cetuximab for cases KRAS/NRAS WT, and bevacizumab). Although the response rate to this combination regime exceeds 50%, progression of the disease is almost universal and only less than 10% of patients are free of disease at 2 years. Current clinical trials with second and third line therapy include new TA, such as tyrosin-kinase receptors inhibitors (MET, HER2, IGF-1R), inhibitors of BRAF, MEK, PI3K, AKT, mTORC, NOTCH and JAK1/JAK2, immunotherapy modulators and check point inhibitors (anti-PD-L1 and anti- PD1). Despite the identification of multiple prognostic and predictive biomarkers and signatures, it is still unclear how expression of many of these biomarkers is modulated by CHT and/or TA, thus potentially affecting response to treatment. In this review we analyzed how certain biomarkers in tumor cells and microenvironment influence the response to new TA and immune-therapies strategies in mCRC pre-treated patients.
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Joan Maurel and Antonio Postigo , Prognostic and Predictive Biomarkers in Colorectal Cancer. From the Preclinical Setting to Clinical Practice, Current Cancer Drug Targets 2015; 15 (8) . https://dx.doi.org/10.2174/156800961508151001102822
DOI https://dx.doi.org/10.2174/156800961508151001102822 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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