二代测序技术检测结直肠癌驱动基因突变分析

目的:用二代测序技术(NGS)检测结直肠癌患者的基因状态特征。方法:收集2016年8月至2020年12月90例结直肠癌患者血液和组织样本,利用NGS技术1021panel进行检测分析驱动基因突变情况。结果:43例组织标本和83份血液标本,同时有血液和组织标本患者36例。组织标本中 KRAS和 B...     

基因突变与结直肠癌靶向治疗的新进展

KRAS基因突变作为表皮生长因子受体(epidermal growth factor receptor,EGFR)单抗疗效预测指标的发现,给转移性结直肠癌(metastatic colorectal cancer,mCRC)的治疗带来了巨大的改变.然而,结直肠癌(colorectal cancer,CRC)的发生涉及到多个癌基因、抑癌基因和信号传导通路的改变,而不同的信号传导通路之间存在着千丝万缕的联系,形成了复杂的信号传导网络.如何寻找使用抗EGFR单抗的适合人群,从而避免不必要的不良反应和无效治疗是目前研究的热点.本文就目前国内外研究较多的预测抗EGFR单抗疗效的生物靶标及相应对策进行综述.     

2017年ESMO结直肠癌领域研究进展解读——基础应用篇

European Society For Medical Oncology（ESMO）大会是欧洲最具影响力的肿瘤专家年度会议。2017年ESMO大会于2017年9月8日至12日在西班牙马德里举行,大会将癌症研究人员和临床医生聚集在一起,开展合作,交流思想,促进实验室到临床以及从临床到实验室的相互转化。现将会议期间有关结直肠癌领域临床前沿及引申的基础研究诸如免疫治疗优化获益人群、转化研究、肿瘤标记物、肿瘤基因型和表型的变化与疾病预后以及治疗方式和/或药物选择的相关性、结直肠癌新靶点等做一简要梳理。     

EGFR靶向治疗在结直肠癌中的研究进展

表皮生长因子受体酪氨酸激酶(EGFR)家族的异常表达和活化,与肿瘤的发生和进展、肿瘤转移关系密切,抑制受体活性可以有效的抑制肿瘤.EGFR信号在结直肠癌形成中具有重要的作用, 随着对肿瘤分子生物学的深入研究,针对EGFR的分子靶向药物已进入结直肠癌治疗的临床研究阶段,此文就EGFR在结直肠癌靶向治疗中的研究进展作一综述.     

2019年结直肠癌领域治疗进展

2019年,结直肠癌领域的进展主要集中在围手术期的治疗模式以及姑息治疗中的免疫治疗和靶向治疗,本文将根据今年大型会议的报道以及重要期刊上的文献作为基础,梳理2019年在结直肠癌治疗领域的进展。     

结直肠癌发生机制研究进展

结直肠癌是最常见的恶性肿瘤之一,其发生由遗传和环境等诸多因素相互作用所致,是一个涉及多基因、多阶段的复杂过程。本文就结直肠癌发生机制包括染色体不稳定（CIN）、微卫星不稳定（MSI）、CpG岛甲基化表型（CIMP）等的研究进展作一综述。     

转移性结直肠癌三线治疗的研究现状及进展

转移性结直肠癌（mCRC）预后较差,其三线治疗仍是一大难题。为进一步延长mCRC患者的生存时间,新型口服药瑞戈非尼、曲氟尿苷/替匹嘧啶（TAS-102）及呋喹替尼已陆续获得批准成为mCRC的标准三线治疗,另有一些有前景的药物也进入了临床研究。本文将综述难治性结直肠癌患者的三线治疗用药选择以及该领域新兴的治疗方案,并探讨用药顺序对患者生存获益的影响。     

Braf基因突变检测方法及其与结直肠癌关系的研究进展

丝裂原活化蛋白激酶（MAPK）通路异常激活在人类多种肿瘤的发生、发展中起重要作用，Braf基因突变是其中的重要环节。该突变的检测方法主要有限制性片段长度多态性（RFIJP）、单链构象多态性（SSCP）、实时荧光聚合酶链反应（PCR）、变性高效液相色谱分析（DHPLC）、基因芯片、直接测序等。遗传性非息肉性结直肠癌（HNPCC）患者不存在Braf基因突变，而结直肠锯齿状病变中该突变较多见。以Braf基因突变为治疗靶点或作为入选标准选取患者．并采用特定药物治疗在结直肠癌的治疗中具有良好的应用前景。     

结直肠癌肝转移新辅助治疗研究进展

结直肠癌的发病率及死亡率在全世界范围内逐年上升,其主要的死亡原因是肝转移。现代医学技术快速发展推动了诊治理念不断更新。个体化治疗及多学科综合治疗协作组（MDT）诊治理念的提出,外科技术以及局部治疗的迅速发展,使患者的生存期得以明显延长。结直肠癌肝转移新辅助治疗的应用有助于降低肿瘤分期,提高手术切除率,进而转化为患者生存获益,这一点在其他实体瘤中也已得到证实。但新辅助治疗是否延长所有患者生存期以及患者能否从局部治疗中获益仍存在争议,本文就结直肠癌肝转移新辅助治疗研究进展进行综述。     

Amelanotic Malignant Melanoma with a BRAF V600E Mutation Mimicking Primary Lung Cancer

Amelanotic melanoma is a rare type of melanoma that shows little or no melanin pigmentation. When tumor lesions are not detected in cutaneous sites, the presence of melanin is the hallmark sign of malignant melanoma. We herein report a case of amelanotic melanoma with a BRAF V600E mutation mimicking primary lung cancer that was finally diagnosed on an autopsy. The current case suggests important caveats for the differential diagnosis of patients with BRAF V600E mutation-positive poorly differentiated lung tumors. In terms of the pathological diagnosis, routine immunohistochemical staining may be useful, especially in patients with a poorly differentiated lung tumor without TTF-1 expression.     

Clinical significance of K-ras and BRAF mutations in Chinese colorectal cancer patients

AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%)...     

BRAF(V600E) mutation and the biology of papillary thyroid cancer

BRAF((V600E)) mutation is the most frequent genetic alteration in papillary thyroid carcinomas (PTCs) that are 80-90% of all thyroid cancers. We evaluated the relationship between BRAF((V600E)) and tumor, host, and environmental factors in PTCs from all geographical areas of Sicily. By PCR, BRAF((V600E)) was investigated in a series of 323 PTCs diagnosed in 2002-2005. The correlation between clinicopathological tumor, host, and environmental characteristics and the presence of BRAF((V600E)) were evaluated by both univariate and multivariate analyses. BRAF((V600E)) was found in 38.6% PTCs, with a 52% frequency in the classical PTCs and 26.4% in the tall cell variant. Univariate analysis indicated that BRAF((V600E)) was associated with greater tumor size (P=0.0048), extra-thyroid invasion (P<0.0001), and cervical lymph nodal metastases (P=0.0001). Multivariate logistic regression analysis confirmed that BRAF((V600E)) was an independent predictor of extra-thyroid invasion (P=0.0001) and cervical lymph nodal metastasis (P=0.0005). The association between BRAF((V600E)) and extra-thyroid invasion was also found in micro-PTCs (P=0.006). In 60 classical PTCs, BRAF((V600E)) was positively correlated with matrix metalloproteinase-9 expression (P=0.0047), suggesting a possible mechanism for BRAF((V600E)) effect on PTC invasiveness. No association was found between BRAF((V600E)) and patient age, gender, or iodine intake. In contrast, a strong association was found with residency in Eastern Sicily (P<0.0001 compared with Western Sicily). These results indicate that BRAF((V600E)) mutation is a marker of aggressive disease in both micro- and macro-PTCs. Moreover, for the first time, a possible link between BRAF((V600E)) mutation and environmental carcinogens is suggested.     

2018年ASCO GI会议结直肠癌诊疗进展

结直肠癌是高发肿瘤,靶向治疗和免疫治疗的出现使得患者生存较前明显改善。2018 ASCO GI会议在结直肠癌早筛研究中发现外周血循环肿瘤细胞（CTC）有助于筛查早期结直肠癌,息肉甲基化检测可以筛选高复发风险患者。而在靶向治疗方向,研究表明,既往接受氟尿嘧啶/奥沙利铂/伊立替康治疗失败的转移性结直肠癌患者,瑞戈非尼序贯西妥昔单抗（R-C）对比相反治疗（C-R）顺序,R-C模式OS更有优势。免疫治疗领域,nivolumab联合CTLA-4抑制剂ipilimumab的双靶向治疗,在dMMR/MSI-H的晚期患者中获得了更好的疗效,同时安全性可控。     

The role of salvage treatment in advanced colorectal cancer

The selection of salvage therapy after first-line treatment failure for metastatic colorectal cancer patients has become more complex with the development of several active drugs in this setting. The addition of oxaliplatin and irinotecan to 5-fluorouracil in the first-line therapy has conditioned the election of the regimen used in second-line, becoming a standard of care the switch between both schedules at the time of disease progression. The recent introduction of new targeted drugs has complicated the scenario even more, allowing different possible combinations in first-, second-, third- and even fourth-line therapy. The role of hepatic arterial infusions has been reconsidered with the availability of new and more active cytotoxic drugs and has become an approach to be taken in mind in the management of these patients. With the possibility of active salvage therapy, surgery rescue approaches should be taken in account during all the course of the patients’ disease.