甲状腺癌的分子靶向治疗进展

甲状腺癌的治疗方法主要以手术为主,但对于转移性的、侵袭性的和晚期的甲状腺癌患者来说,手术效果有限,而且碘放射治疗和化疗对这些恶性程度较高的肿瘤治疗效果往往不太理想,因此分子靶向治疗的出现则为这些患者带来了新的希望。本文将从甲状腺癌发病的分子机制,分子靶向治疗药物的作用机制、治疗效果和不良反应等方面作一综述。     

软组织肉瘤分子靶向治疗临床研究进展

软组织肉瘤(STS)发生中会涉及某些异常分子和基因,使用针对特定分子和基因靶点的药物,选择性杀伤肿瘤细胞,较传统化疗更有效,不良反应更小.但目前绝大多数STS的有效作用靶点尚不明确,试验性靶向治疗疗效多不理想,多靶点药物可能是今后STS靶向治疗的研究方向.     

软组织肉瘤靶向治疗进展

化学治疗晚期软组织肉瘤疗效似已达到平台,靶向药物是进一步提高疗效的关键.尽管第1代靶向治疗药物开发的种类繁多,但仅有少数药物在前瞻性、随机的Ⅲ期临床试验中显示出生存优势.第2代靶向治疗药物多靶点抑制剂可同时阻断肿瘤多个信号传导,临床试验的初步结果表明,不良反应可以耐受,效果较好,治疗软组织肉瘤已显示出较好的应用前景.     

分子靶向药物在肺癌治疗中的临床进展

人类表皮生长因子受体(human epidermal growth factor receptor,EGFR)家族由四个受体成员构成:HER1(亦称c-erbB1,EGFR)、HER2(亦称c-erbB2,neu)、HER3(c-erbB3)及HER4(c-erbB4).EGFR是一分子量为170 kD的跨膜糖蛋白,有配体依赖性的酪氨酸激酶活性,存在于大多数细胞中,在多种肿瘤中都有过表达,如非小细胞肺癌(NSCLC)中鳞癌EGFR表达率为85%,腺癌和大细胞癌为65%,而小细胞肺癌罕见EGFR表达.EGFR高表达的肿瘤细胞增长迅速,容易发生转移,复发率高,因此被认为是非小细胞肺癌靶向治疗的一个比较理想的分子靶点.阻断EGFR信号传导通路有两种方法:(1)酪氨酸激酶抑制剂与EGFR胞内部分的磷酸化酶位点结合,阻止磷酸化酶的活化.目前已有多种药物开发,以吉非替尼和Erlotinib为代表.(2)单克隆抗体与HER的胞外区结合从而阻断其活化.以HER2特异性的Herceptin及HER1/EGFR特异性单抗Cetuximab(C-225)为代表.     

肿瘤分子靶向治疗的新观点

传统的细胞毒药物治疗肿瘤疗效已经达到了平台,单克隆抗体类靶向药物与化疗联合应用成为进一步提高疗效的关键.尽管靶向药物的特定性标靶人群尚未明确,但根据检测基因及蛋白状态、分子标准和临床标准选择合适的靶向药物已显示一定的应用前景.     

乳腺癌分子靶向治疗进展

分子靶向治疗是当今肿瘤治疗领域的热点,代表了肿瘤药物治疗的最新发展方向。在乳腺癌领域里,目前已广泛用于临床治疗;或已在我国进行临床试验,获得较好疗效,有望上市的分子靶向治疗共有四种,介绍如下。1赫赛汀用于HER2过表达乳腺癌的治疗赫赛汀(曲妥珠单抗)是一种人源化单克隆     

肺癌分子靶向治疗新进展

近几年来 ,肺癌的分子靶向治疗取得了较大的进展 ,靶向治疗新药不断涌现 ,在临床试验或正式临床应用中取得非常鼓舞人心的结果 ,其中最引人注目的有Iressa (ZD183 9,Gefitinib)、OSI774(Tarceva ,erlotinib)、Herceptin(Trastuzumab ,贺赛汀 )、IMC C2 2 5 (cetuximab ,Erbitux)和Bevacizumab(Avastin)等。     

肿瘤分子靶向治疗进展

随着对肿瘤细胞生长、增殖、凋亡的分子机制研究的深入,使人类靶向性治疗肿瘤成为可能.针对肿瘤的特异性分子靶点设计的治疗方案,具有治疗特异性强、基本不损伤正常组织的优点,是肿瘤治疗中最有前景的方案.目前,全球有80余种“靶向治疗”制剂已经或正在进行临床试验,以肿瘤血管生成和表皮生长因子受体（EGFR）为靶点的药物占总数的一半以上.     

胃癌分子靶向治疗的进展

分子靶向治疗是近年来肿瘤治疗领域中的研究热点,已在胃肠间质瘤、淋巴瘤、乳腺癌、结直肠癌、非小细胞肺癌等治疗中显示出高效、低毒等特点。有关胃癌分子靶向治疗的研究已取得了不少进展,这些研究主要针对EGFR通路、抗血管生成、细胞周期素激酶以及NF—κB信号传导通路等。本文就此进行综述。     

肿瘤的靶向治疗

靶向治疗通过针对肿瘤特异性的靶点来杀死和抑制肿瘤细胞，避免了对正常细胞的伤害，成为目前肿瘤研究的热点之一。近几年来，靶向治疗新药不断涌现，在许多临床试验或正式临床应用中取得很好的疗效。     

食管癌分子靶向治疗

与传统细胞毒性化疗相比,分子靶向治疗能更特异地作用于肿瘤而毒性反应较轻.分子靶向治疗是一种全新治疗模式,食管癌的分子靶向治疗的临床研究才刚刚开始.     

Molecular targeted therapy for advanced hepatocellular carcinoma

Systemic anticancer therapy for hepatocellular carcinoma (HCC) is limited by intrinsic drug resistance and accompanying liver dysfunction. However, recent advances in molecular targeted therapy (MTT) have shed light on the treatment of advanced HCC. A recent randomized, placebo-controlled trial demonstrated that sorafenib, a multi-target tyrosine kinase inhibitor, prolonged overall survival and time-to-progression in patients with advanced HCC. This breakthrough highlights the potential of MTT targeting hepatocarcinogenic pathways, such as the Raf/MAPK/ERK pathway, angiogenic pathways and the EGFR signaling pathway. This review discusses the current status and the potential of developing novel MTTs for advanced HCC.     

Molecular pathogenesis and targeted therapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) constitutes the 5th most frequent cancer worldwide, and due to a lack of treatment options, HCC represents the 3rd most lethal cancer worldwide. The incidence of HCC is continuously rising in Europe and Northern America, which can be explained by spreading of hepatitis C virus infections. Systemic chemotherapy is not an option for most patients with HCC. The most promising strategy for systemic treatment of HCC is targeted therapy. Successful targeted therapy has to inhibit pathways which are necessary for tumor growth, even in the late stages of carcinogenesis. The p16/Rb, p53, and IGF2R checkpoints as well as oncogenic alterations of telomerase, c-myc, Wnt/beta-catenin, PI3K/Akt, hedgehog, and c-met/HGF are most frequently involved in human hepatocarcinogenesis. However, currently, the most attractive target for molecular therapy of HCC appears to be the vascular endothelial growth factor (VEGF). Phase I/II studies showed high progression-free survival rates with antibodies or small molecules targeting the VEGF receptor pathway. Recently, a randomized placebo-controlled phase III study showed that the multikinase inhibitor sorafenib, which inhibits VEGF and Raf, significantly improves survival of patients with advanced HCC and Child A cirrhosis. As a consequence of this study, sorafenib is now the first available drug for effective systemic treatment of patients with advanced HCC.     

Molecular targeted therapies in hepatocellular carcinoma

In vivo tumor progression requires the supply of oxygen and nutrition by neovasculature. Hepatocellular carcinoma (HCC) is one of the typical tumors with neovascularization, and the dramatic alteration in the arterial vascularity may lead to acquisition of the potential for vascular invasiveness and metastasis. In 2008, phase III clinical trials revealed anti-angiogenic agent "sorafenib" as the first drug that demonstrated an improved overall survival in patients with advanced HCC. A new era of HCC treatment had arrived, but there has been limited further improvement in survival benefits. This review summarizes molecular targeted therapy with a focus on angiogenesis, growth signals, and mitotic abnormalities, as well as the promising concepts of "cancer stemness" and "synthetic lethality" for the strategy of targeted therapy.     

Molecular targeted therapy in gastrointestinal cancer

Gastrointestinal cancer is one of the highly prevalent malignant diseases worldwide which is a major cause of morbidity and mortality. Gastric cancer is the second leading cause of cancer mortality in the world and its management, especially in advanced stages, has evolved relatively little[1]. Colorectal cancer (CRC) remains the third most common malignancy and the third leading cause of cancer death worldwide[2]. The surgical treatment is still the most effective therapy for the gastrointestinal cancer. However, the majority of the patients had lost the opporunity of surgical therapy when it was detected at advanced stage, so to seek means other than surgical treatment of gastrointestinal cancer metastasis and recurrence also has an important significance. With the deeping research of the molecular biology, molecular targeted therapy has become the hotspot and focus of comprehensive treatment of gastrointestinal cancer which is proposed against the molecular biological targets such as tumor cell growth, apoptosis, cell cycle, invasion and angiogenesis. Molecular targeted therapy can be grouped into six main areas: the epidermal growth factor receptor (EGFR) inhibitors, anti-angiogenic factors, cell cycle inhibitors, apoptosis promoters and matrix metalloproteinase inhibitors, cyclooxygenase inhibitors. The review of the progress are as follows.     

胃肠癌分子靶向治疗

Gastrointestinal cancer is one of the highly prevalent malignant diseases worldwide which is a major cause of morbidity and mortality. Gastric cancer is the second leading cause of cancer mortality in the world and its management, especially in advanced stages, has evolved relatively little [1]. Colorectal cancer (CRC) remains the third most common ma-lignancy and the third leading cause of cancer death worldwide [2]. The surgical treatment is still the most effective therapy for the gastrointestinal cancer...     

Molecular targeted therapy of glioblastoma

Glioblastomas are intrinsic brain tumors thought to originate from neuroglial stem or progenitor cells. More than 90% of glioblastomas are isocitrate dehydrogenase (IDH)-wildtype tumors. Incidence increases with age, males are more often affected. Beyond rare instances of genetic predisposition and irradiation exposure, there are no known glioblastoma risk factors. Surgery as safely feasible followed by involved-field radiotherapy plus concomitant and maintenance temozolomide chemotherapy define the standard of care since 2005. Except for prolonged progression-free, but not overall survival afforded by the vascular endothelial growth factor antibody, bevacizumab, no pharmacological intervention has been demonstrated to alter the course of disease. Specifically, targeting cellular pathways frequently altered in glioblastoma, such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), the p53 and the retinoblastoma (RB) pathways, or epidermal growth factor receptor (EGFR) gene amplification or mutation, have failed to improve outcome, likely because of redundant compensatory mechanisms, insufficient target coverage related in part to the blood brain barrier, or poor tolerability and safety. Yet, uncommon glioblastoma subsets may exhibit specific vulnerabilities amenable to targeted interventions, including, but not limited to: high tumor mutational burden, BRAF mutation, neurotrophic tryrosine receptor kinase (NTRK) or fibroblast growth factor receptor (FGFR) gene fusions, and MET gene amplification or fusions. There is increasing interest in targeting not only the tumor cells, but also the microenvironment, including blood vessels, the monocyte/macrophage/microglia compartment, or T cells. Improved clinical trial designs using pharmacodynamic endpoints in enriched patient populations will be required to develop better treatments for glioblastoma.     

肝癌靶向治疗靶点的研究进展

随着现代医学的不断发展,医疗整体水平的进一步提高,肝癌的治疗手段已经不仅仅局限于几种传统手段,如手术切除、放射治疗和化学治疗,众多医学同仁正致力于研发更加有效的治疗手段。自20世纪80年代起,靶向治疗走进了人们的视线,经过不断的探索和研究,正逐渐成为肝癌治疗的主要途径之一。据报道肝癌的靶向治疗方法多种多样,但都不同程度地提高了肝癌的治疗效果,本文主要从受体靶点、肽靶点、标志性分子靶点这三个方面进行概述。     

以RET为靶点治疗甲状腺髓样癌

甲状腺髓样癌(MTC)是甲状腺滤泡旁细胞的恶性肿瘤,分为散发型和遗传型,它是MEN2A、MEN2B和FMTC 3种遗传性综合征共同的临床特征.RET原癌基因编码跨膜的酪氨酸激酶受体,该基因的突变及多态性可以通过不同的信号转导途径激活RET酪氨酸激酶区引起MTC的发生.目前,RET原癌基因已被作为MTC分子治疗的靶点,但尚无针对RET基因相关肿瘤的有效治疗策略.