原发性肝癌分子靶向治疗临床研究进展

随着分子生物学技术的发展,分子靶向治疗已成为21世纪肿瘤治疗的主要方向和潮流.针对VEGF/VEGFR、EGFR、Raf-MAPK-ERIC、HGFR等靶点的分子靶向治疗以及与其他治疗的联合治疗开始用于原发性肝癌的临床,并在一些临床试验中取得了令人鼓舞的结果.针对原发性肝癌的分子靶向治疗的临床研究进展进行综述.     

胃癌的靶向治疗研究进展简

近年来,手术、化疗、放疗在胃癌治疗方面取得了一定的进步,然而进展期胃癌疗效仍不理想.靶向治疗在胃癌的应用逐渐受到越来越多的关注.目前,已有众多的Ⅱ/Ⅲ期临床试验用于评估胃癌分子靶向治疗疗效,针对Her-2的分子靶向治疗已取得突破性进展,更多的靶点和靶向药物有待发掘.     

乳腺癌分子靶向治疗现状

近年来,乳腺癌的分子靶向治疗取得了长足的发展.曲妥珠单抗联合化疗已成为Her-2阳性乳腺癌患者的标准一线治疗.全文从抗Her-2治疗药物-PI3K/AKT/mTOR通路中的抑制剂,抗血管生成治疗药物,针对BR-CA1/2突变的PARP抑制剂,细胞周期蛋白依赖性激酶4和6(CDK4/6)抑制剂几个方面就当前乳腺癌分子靶向治疗现状作一综述.     

分子靶向药物在肝细胞肝癌治疗中的研究进展

对于不适宜手术切除的晚期肝细胞肝癌,传统的化疗并不能改善患者的预后。分子靶向药物的出现为肝细胞肝癌的治疗提供了新的治疗手段。分子靶向药物治疗肝细胞肝癌的临床试验中,包括多靶点抑制剂、血管内皮生长抑制剂、小分子酪氨酸激酶抑制剂以及分子靶向药与化疗的联合等已经显示出了潜在的疗效和良好的发展前景。临床试验显示索拉非尼可延长肝细胞肝癌的中位无疾病进展时间至9.2个月,中位总生存至10.5个月,贝伐单抗与厄洛替尼联合治疗肝细胞肝癌延长中位总生存达68周。本文针对肝细胞肝癌使用多靶点抑制剂、血管内皮生长抑制剂等的临床研究进展进行综述。     

原发性肝癌的治疗进展

肝癌是我国常见的恶性肿瘤之一,预后很差。随着对肝癌认识的深入和技术手段的改进,肝癌的手术和药物治疗都取得了可喜的进展。本文就近年来不同类型肝癌的手术治疗、系统化疗和分子靶向治疗等方面的进展作一阐述。     

原发性肝癌的治疗进展

肝癌是我国常见的恶性肿瘤之一,预后很差.随着对肝癌认识的深入和技术手段的改进,肝癌的手术和药物治疗都取得了可喜的进展.本文就近年来不同类型肝癌的手术治疗、系统化疗和分子靶向治疗等方面的进展作一阐述.     

索拉非尼治疗原发性肝癌的研究进展

原发性肝癌是我国高发常见的恶性肿瘤，起病隐袭，早诊困难，确诊时大多数已达局部晚期或远处转移，治疗棘手，预后很差；常规化疗药物的作用有限，没有证据显示有明显的生存获益。已知肝癌的发病机制十分复杂，其发生、发展和转移与多种基因突变、细胞信号传导通路和新生血管增生异常密切相关，其中存在着多个关键性环节，正是采用分子靶向治疗的理论基础和潜在的靶点。近年来，应用分子靶向药物治疗肝癌的研究逐渐受到重视，正在成为新的热点，而多靶点、多激酶抑制剂索拉非尼（多吉美）作为代表性药物，已经取得突破性成果，能够有效地延长晚期患者的生存时间，开创了肝癌靶向治疗的新时代。为了尽快地熟悉了解有关动态，本文全面而系统地综述了索拉非尼治疗肝癌的实验研究、临床上单药和联合治疗研究的新进展，并讨论展望了未来的发展方向。     

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。     

逆转晚期原发性肝癌化疗耐药的研究进展

姑息化疗是晚期原发性肝癌的主要治疗手段,但化疗耐药常常是治疗失败的主要因素之一。本文对靶向抑制细胞周期G2检查点、靶向PI3K/Akt/mTOR信号传导通路、抑制肿瘤对乏氧的反应、节拍化疗联合分子靶向药物抗血管生成和热疗化疗联合以及癌细胞微量元素调控等逆转原发性肝癌化疗耐药的研究进展作一综述。     

肝癌分子靶向药物的研究进展

原发性肝癌是我国常见的恶性肿瘤,其发病隐袭,进展迅速,发现时多数已失去手术机会,因此预后极差。对于晚期肝癌,索拉非尼是唯一有生存获益的分子靶向药物,该药自2007年上市以来,引起了肝癌分子靶向药物的研究热潮,但遗憾的是,此后未再有新的药物批准用于临床。本文就分子靶向药物在肝癌领域临床研究的相关热点问题作一综述。     

Biomarker-Driven and Molecular Targeted Therapies for Hepatobiliary Cancers

The recent accumulation of molecular profiling data for primary hepatobiliary malignancies, including hepatocellular carcinoma and biliary tract cancers, has led to a proliferation of promising therapeutic investigations in recent years. Treatment with pathway-specific targeted inhibitors and immunotherapeutic agents have demonstrated promising early clinical results. Key molecular alterations in common hepatobiliary cancers and ongoing interventional clinical trials of molecularly targeted systemic agents focusing on hepatocellular carcinoma and biliary tract cancer are reviewed.     

Molecularly targeted therapy for advanced hepatocellular carcinoma in 2012: current status and future perspectives

Improving the overall survival for patients with advanced hepatocellular carcinoma (HCC) requires development of effective systemic therapy. Despite the successful approval and extensive application of sorafenib, the prognosis for patients with advanced HCC remains poor and the benefits with sorafenib are modest. In the past few years, there have been renewed and continued interests and active research in developing other molecularly targeted agents in HCC. While the initial efforts are focusing on anti-angiogenic therapy, other agents targeting the epidermal growth factor-receptor, mammalian target of rapamycin (mTOR), hepatocyte growth factor/c-Met among others have entered HCC clinical trials. Combining different molecularly targeted agents or combining targeted agents with chemotherapy represent other strategies under investigation. This review will attempt to summarize the current status of other molecularly targeted agents or regimens beyond sorafenib under development in advanced HCC and the future perspectives.     

肝癌的靶向治疗

肝癌（HCC）是全球最富有挑战性的恶性肿瘤之一。HCC需要综合治疗，目前尚无特效的治疗药物。分子靶向药物的发展，使HCC的全身治疗有了新的希望。阐述了分子靶向药物的现状，多激酶抑制剂、抗血管生成和抗表皮生长因子受体药物在临床上的进展，认为索拉芬尼是晚期HCC的新的标准治疗药物。     

Molecularly targeted therapy in head and neck cancer

The emergence of molecularly targeted therapy did not spare head and neck cancers. Head and neck squamous cell carcinomas (HNSCC) were indeed one of the first tumor types to get a molecularly targeted agent approved (cetuximab, a monoclonal antibody targeting EGFR), not only in the recurrent or metastatic setting but also in the locally advanced setting. However, the development of molecularly targeted agents inhibiting non-EGFR targets appears to be complex. This article summarizes recent data on molecularly targeted agents in most frequent head and neck cancers including HNSCC, nasopharyngeal carcinoma and adenoid cystic carcinoma of salivary glands. Challenges for the development of these agents are then discussed.     

Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma

It is well appreciated that hepatocellular carcinoma (HCC) represents one of the most challenging malignancies of worldwide importance. In fact, HCC is the fifth most common cancer and the third most common cause of cancer-related death globally. The incidence rates for HCC in the U.S. and Western Europe have been rising. Unresectable or metastatic HCC carries a poor prognosis, and systemic therapy with cytotoxic agents provides marginal benefit. Because of the poor track record of systemic therapy in HCC, there has been a sense of nihilism for this disease in the oncology community for decades. However, with the arrival of newly developed, molecularly targeted agents and the success of some of these agents in other traditionally challenging cancers, such as renal cell carcinoma, there has been renewed interest in developing novel systemic therapy in HCC. At the recent Annual Meeting of the American Society of Clinical Oncology, results of a phase 3, randomized, placebo-controlled trial were presented in which sorafenib demonstrated improved survival in patients with advanced HCC. This landmark study represents the first agent that has demonstrated an improved overall survival benefit in this disease and sets the new standard for first-line treatment of advanced HCC. For this review, the author concisely summarized the current status of molecularly targeted agents that are under clinical development in advanced HCC.     

Current challenges for the early clinical development of anticancer drugs in the era of molecularly targeted agents

The emergence of molecularly targeted agents in oncology has not only revolutionized the care of cancer patients, but also changed the daily practice of medical oncologists. Molecularly targeted agents indeed often differ from traditional cytotoxic agents by their administration schedules and routes, their toxicity profiles, and/or the assessment of their antitumor activity. In addition, the observation that molecularly targeted agents sometimes have limited antitumor activity as single agents has led clinical investigators to combine molecularly targeted agents together or with cytotoxic agents. We review here the current challenges for the early clinical development of anticancer agents in the era of molecularly targeted agents. We focus on the choice of end points in phase I oncology clinical trials, as well as on the choice of dose escalation methods with an emphasis on available dose escalation methods for molecularly targeted agents and for combination trials.     

Targeted agents for the systemic treatment of advanced hepatocellular carcinoma

The prognosis for advanced hepatocellular carcinoma is poor and systemic therapy has historically been of limited benefit. However, novel targeted agents offer promise in improving patient outcomes. In a recent phase III study the oral multi-tyrosine kinase inhibitor sorafenib was demonstrated to have a survival advantage over a placebo in advanced hepatocellular carcinoma. Similar efficacy was demonstrated in a phase III trial limited to an Asian–Pacific group of patients. While these results are encouraging, it is vital to make further progress. In this review we examine current knowledge of targeted agents in advanced hepatocellular carcinoma. We also address some of the key issues that require exploration regarding the use of targeted agents in advanced hepatocellular carcinoma.     

Targeted therapy for locally advanced renal cell carcinoma

A number of molecularly targeted agents are now available for patients with metastatic renal cell carcinoma. Their role in locally advanced disease is not well defined, and the mechanisms of progression in the high-risk patient are poorly understood. For an agent to be effective in locally advanced renal cell carcinoma it needs to be able to downstage primary tumors, and to prevent the formation of metastases. In this review, we summarize clinical trials assessing the ability of these new agents to cytoreduce primary tumors, and explore available evidence on their ability to prevent the formation of metastases. Ongoing adjuvant clinical trials assessing molecularly targeted agents in the high-risk setting will provide valuable information on their utility in this patient population. Future trials using agents with optimized cytoreductive capabilities in conjunction with therapies capable of preventing metastatic dissemination may improve the outcomes of patients with locally advanced renal cell carcinoma.     

Nanomedicine in management of hepatocellular carcinoma: Challenges and opportunities

Hepatocellular carcinoma is the second leading cause of cancer deaths worldwide. It is characterized by unique features that can be utilized for selective and targeted therapy, which aids in preserving healthy tissues from deteriorating effects of traditional chemotherapeutics. In this minireview, a brief overview of recent drug delivery attempts for the management of hepatocellular carcinoma with the aid of nanomedical structures is presented. The beneficial impact of nanomaterials in terms of prolonged retention in blood and target sites, controlled biodistribution and improved stability of the encapsulated payloads, will be described, together with the possibility of incorporating more than one cargo into the same nanostructure. Incorporation of stimuli‐responsive components, decoration with targeting moieties and the use of molecularly targeted drugs for treatment of hepatocellular carcinoma are also highlighted.