大肠癌的靶向治疗

癌症靶向治疗(targeted cancer therapy)是癌症治疗的新纪元,是建立在肿瘤分子生物学研究基础上,靶向治疗主要可以归纳为4个方面:①针对表皮生长因子受体(EGFR通道的靶向治疗;②针对血管内皮生长因子(VEGF)通道的靶向治疗;③基质金属蛋白酶(MMP)抑制剂;④选择性环氧化酶-2(COX-2)抑制剂,其中EGFR和VEGF是目前最为主要的靶点,有多种药物均是针对此靶点,且在临床试验或临床应用中取得很好疗效。1对表皮生长因子受体(EGFR)通道的靶向治疗人EGF受体(human epidermal growth factor receptor,HER)家族由4个成员组成,分别称为HER1(…     

脂肪肉瘤的靶向治疗研究进展

脂肪肉瘤是起源于间叶组织的恶性肿瘤,是较为常见的软组织肉瘤亚型之一,由于其对放疗和化疗不敏感,早期根治性手术是其首选的治疗方式.尽管进行了彻底的手术切除,但术后局部复发率仍然很高,患者的预后较差.因此,寻找驱动脂肪肉瘤发生发展的潜在分子机制及治疗靶点的相关转化研究和临床试验已成为近年来临床研究的热点.本文总结脂肪肉瘤潜...     

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...     

大肠癌分子靶向治疗

大肠癌为消化道常见恶性肿瘤之一，但传统的化疗效果仍不理想。新近在分子靶向治疗方面已经取得了实质性的进展，其高效低毒的特性越来越引起人们的重视。本文就目前在大肠癌分子靶向治疗方面的新进展进行综述。     

大肠癌靶向治疗现状

大肠癌(colorectal cancer,CRC)是世界第三大常见肿瘤,2008年全球新发病例120万,死亡608 700例,40%～50%的患者发生转移。病变早期手术,患者5年生存率可以达到90%,而转移性大肠癌(metastatic colorectal cancer,mCRC)患者5年生存率仅为10%。mCRC的治疗在过去几十年得到了长足的进步,随着肿瘤发生发展过程中分子通路和生物进程机制的不断明了,靶向治疗药物开始出现并应用于临床。目前批准用于大肠癌临床治疗的靶向药物有贝伐单抗、西妥昔单抗、帕尼单抗三种。     

大肠癌肝转移的分子靶向治疗进展

大肠癌(colorectal cancer,CRC)是全球第3大恶性肿瘤,在我国是第5大常见肿瘤。目前,CRC的5 a生存率仅60%左右,肝转移是主要的死亡原因之一。大约40%的CRC患者最终死于癌肿转移,肝脏是最常见的转移部位,近50%的CRC患者会发生肝转移,15%～25%的CRC患者确诊时即伴有肝转移,另有约     

以分子分型为基础的肺癌靶向治疗研究进展

随着基因分析技术的不断发展, 对肿瘤的发病机制以及治疗的研究愈加透彻。依靠传统的组织病理学分类无法充分实现对肿瘤患者的个体化治疗方案选择在制定临床研究的方案时, 研究者在考虑病理类型和临床因素之外, 还要充分考虑受试个体的基因特征。那么, 分子异常改变对肿瘤治疗意义如何, 以基因特征为基础的肿瘤临床试验时代离我们到底有多远?本文在此将可能影响肿瘤治疗方向的基因改变类型, 以及近年肺癌研究领域一系列基于分子特征的临床试验做一综述。      

大肠癌靶向治疗进展

大肠癌是最常见的恶性肿瘤之一，近年来靶向治疗的成功应用为大肠癌患者带来了新的希望。针对血管内皮生长因子（VEGF）和表皮生长因子受体（EGFR）的单克隆抗体（贝伐单抗和西妥昔单抗）已在临床上广泛应用。本文就目前大肠癌靶向治疗方面的新进展进行综述。     

胃癌靶向治疗的研究进展

目前手术仍是治疗胃癌的主要手段,但后续发生的复发和转移,使得仅有30%～40%比例的胃癌患者可从中获益,因而寻求手术以外的途径成为胃癌综合治疗的重点和热点。靶向治疗已经成为诸多实体瘤的新型治疗模式,胃癌在分子靶向治疗方面也取得实质性的进展,如ToGA试验,为晚期胃癌的靶向治疗掀开了新的篇章;但因缺乏充分的循证医学依据,具体的治疗方案至今仍未能明确。文章就其作用的不同靶点,如EGFR通路、血管生成、靶向NF-κB信号传导通路以及细胞周期素激酶抑制剂等等,在胃癌中的研究和临床应用进行简要综述。     

食管癌靶向治疗的研究进展

摘 要：近年来由于手术、化疗和放疗技术的发展,食管癌的临床治疗有了很大的进展,但5年总生存率仍然较低。分子靶向治疗通过作用于肿瘤细胞特定靶点,在多种肿瘤中显示出了良好的疗效。在食管癌的治疗中也相继有一些药物进行了临床探索和应用。但在EGFR、HER2+、VEGF、c-MET、PI3K/Akt/mTOR等通路的靶向药物中多数Ⅱ、Ⅲ期临床研究结果令人失望。酪氨酸蛋白激酶抑制剂和血管内皮生长因子单克隆抗体在部分食管癌人群中显示出一定的生存受益。当然,还有一些新靶向药物（PD-1单克隆抗体、c-MET通路的单克隆抗体）研究结果值得期待。但目前大多数食管癌相关靶向研究均来自于西方人群的食管腺癌或食管胃结合部癌,国内数据相对缺乏,我们期待国内进行的尼妥珠单抗的临床研究能带来振奋人心的结果。     

Biomarker-driven and molecular targeted therapies for colorectal cancers

Improved clinical selection and identification of new molecules and innovative strategies have widened treatment options and increased overall survival in metastatic colorectal cancer patients in recent years. Biomarker-driven therapies represent an emerging issue in this field and new targeted treatments are under investigation and probably will be soon adopted into daily clinical practice. In the present review, the role RAS, BRAF mutations, Her2 amplification, microsatellite instability, and CpG island methylator phenotype are discussed according to their possible roles as prognostic, predictive markers, as well as possible biomarker-driven treatment options.     

New targeted therapies in gastrointestinal cancers

Opinion statement Despite surgical, radiotherapeutic, and chemotherapeutic advances, a large proportion of gastrointestinal (GI) cancers remain incurable. An improved understanding of the molecular pathogenesis of cancer has promulgated the development of novel agents designed to target critical pathways involved in cancer development and progression. The crucial role of the epidermal growth factor receptor (EGFR) in tumor proliferation and the overexpression of EGFR in several GI cancers provides the rationale for targeting and interrupting this key signaling network. EGFR blockade through monoclonal antibodies (C225 and ABX-EGF) and tyrosine kinase inhibitors (ZD1839 and OSI-774) has translated into promising evidence of clinical benefit. Ras-mediated signal transduction has been targeted using inhibitors of farnesyl transferase (R115777 and SCH66336) to block the post-translation modification of Ras. Inhibitors of vascular growth factor receptor (bevacizumab and PTK787) and matrix metalloproteinase target the effects of the host environment. Cyclooxygenase-2 inhibitors in colorectal cancer and STI571 in GI stromal tumors represent novel therapies of interest for these specific GI cancers. Evidence suggests that novel agents can be administered alone or in combination with standard therapies with little additional toxicity. The results of ongoing and future research efforts will clarify the optimal use and survival benefit of targeted therapies for patients with GI malignancies.     

A review of cutaneous toxicities from targeted therapies in the treatment of colorectal cancers

Currently there are three targeted therapies approved for the treatment of colorectal cancers. These include the epidermal growth factor receptor (EGFR) inhibitors, cetuximab and panitumumab, and the multikinase inhibitor regorafenib. It is important to understand and recognize the common presentations of cutaneous toxicity that result from these agents to effectively manage symptoms and prevent premature discontinuation of anticancer treatment.Key Words: Cetuximab, panitumumab, regorafenibCurrently there are three targeted therapies approved for the treatment of colorectal cancers. These include the epidermal growth factor receptor (EGFR) inhibitors, cetuximab and panitumumab, and the multikinase inhibitor regorafenib. It is important to understand and recognize the common presentations of cutaneous toxicity that result from these agents to effectively manage symptoms and prevent premature discontinuation of anticancer treatment.     

Molecularly targeted therapies for malignant gliomas: advances and challenges

The identification of molecular markers associated with tumor but not with normal tissue has allowed the development of highly specific, targeted therapies for the treatment of cancer. Over the last several years, tremendous advances in our understanding of the genetic and molecular changes involved in the progression of malignant gliomas have triggered a large effort in the development of targeted therapies to treat these tumors. However, to date only a modest clinical benefit, limited to subsets of patients, has been demonstrated. Furthermore, despite a high degree of target selectivity, the use of targeted therapies often has systemic toxicity. The reasons behind this limited clinical success are complex and include the intricacy of the signaling pathways in gliomas and the heterogeneity of the disease process, compounded by existing limitations in assessing the efficacy of these novel agents when conventional end points and clinical trial designs are utilized. However, despite these difficulties targeted therapies remain a very attractive avenue of treatment for malignant gliomas. Three basic approaches are needed to overcome the hurdles associated with targeted therapies: first, further development of genetic profiling techniques will help to better determine the genetic changes and molecular pathways involved in gliomas and will potentially allow the design of individualized therapies based on the genetic and molecular signature of each tumor. Second, there is a need for the development of better combination strategies (complementary targeted agents or targeted agents with chemotherapy drugs) directed towards disease heterogeneity. Third, we need to optimize the design of preclinical and clinical trials to obtain the maximum amount of information in the shortest period of time.     

Molecularly targeted therapies for malignant gliomas: advances and challenges

The identification of molecular markers associated with tumor but not with normal tissue has allowed the development of highly specific, targeted therapies for the treatment of cancer. Over the last several years, tremendous advances in our understanding of the genetic and molecular changes involved in the progression of malignant gliomas have triggered a large effort in the development of targeted therapies to treat these tumors. However, to date only a modest clinical benefit, limited to subsets of patients, has been demonstrated. Furthermore, despite a high degree of target selectivity, the use of targeted therapies often has systemic toxicity. The reasons behind this limited clinical success are complex and include the intricacy of the signaling pathways in gliomas and the heterogeneity of the disease process, compounded by existing limitations in assessing the efficacy of these novel agents when conventional end points and clinical trial designs are utilized. However, despite these difficulties targeted therapies remain a very attractive avenue of treatment for malignant gliomas. Three basic approaches are needed to overcome the hurdles associated with targeted therapies: first, further development of genetic profiling techniques will help to better determine the genetic changes and molecular pathways involved in gliomas and will potentially allow the design of individualized therapies based on the genetic and molecular signature of each tumor. Second, there is a need for the development of better combination strategies (complementary targeted agents or targeted agents with chemotherapy drugs) directed towards disease heterogeneity. Third, we need to optimize the design of preclinical and clinical trials to obtain the maximum amount of information in the shortest period of time.     

胆系肿瘤化疗及其分子靶向治疗

 胆系肿瘤是一种起源于胆管上皮的恶性肿瘤。多数患者发病时已达局部晚期或已发生远处转移。尽管系统化疗方案层出不穷,但是无法行手术切除的患者预后极差。吉西他滨与顺铂联合方案化疗可显著延长患者的生存期,是目前局部晚期或转移性胆系肿瘤化疗的标准方案。应用分子靶向药物治疗进展期胆系肿瘤是临床研究的新趋势。     

从2010年美国临床肿瘤学会会议看结直肠癌靶向治疗

近年来的关于结直肠癌靶向治疗的研究逐渐从晚期的姑息治疗扩展到新的领域,如维持治疗和辅助治疗等,同时关于预后和疗效预测标记物的研究也逐渐深入.这些研究正逐渐引起现有临床治疗策略的变化.关于结直肠癌靶向治疗2010年美国临床肿瘤学会会议上发布的数据给人们一些新的发现和启示.     

Targeted therapies in the treatment of colorectal cancers.

BACKGROUND: In solid organ malignancies, no tumor type has seen a greater impact from the development of novel targeted therapies in 2004 than metastatic colorectal cancer. METHODS: We review the current progress to date with the use of monoclonal antibodies in colorectal cancer and look at newer therapies under investigation. RESULTS: Two monoclonal antibodies received Food and Drug Administration approval in early 2004, both for the indication of advanced, metastatic colorectal cancer. A large, randomized, placebo-controlled study demonstrated that the addition of a monoclonal antibody to vascular endothelial growth factor, bevacizumab, led to a statistically significant improvement in overall survival, with tolerable additional toxicity. Chimeric monoclonal antibody therapy directed at the epidermal growth factor receptor was associated with radiographic responses in a significant minority of patients with irinotecan-refractory colon cancer in a randomized phase II study of patients with irinotecan-refractory disease. CONCLUSIONS: These dramatic successes have led to further clinical studies of targeted therapy in colorectal cancer, making it one of the most promising areas of cancer research.     

Differentiated thyroid cancers: a comprehensive review of novel targeted therapies

Differentiated thyroid carcinoma (DTC) accounts for more than 90% of new thyroid cancer diagnoses, and includes papillary, follicular and Hürthle cell carcinoma. The prognosis for the vast majority of individuals diagnosed with DTC is excellent, with current treatment that includes surgery, radioactive iodine ablation and postoperative thyroid-stimulating hormone suppression. Unfortunately, the small proportion of individuals who develop radioactive iodine-resistant recurrent disease have few treatment options, and the vast majority will eventually die from their disease. Recently, several novel targets for anticancer agents have been identified and offer new hope for thyroid cancer patients diagnosed with progressive disease. In addition to targeting genes commonly altered in thyroid cancer, which include mutations in BRAF, RAS and RET, proangiogenic growth factor receptors and the sodium-iodide symporter have also been targeted. Several clinical trials evaluating tyrosine kinase and angiogenesis inhibitors for treatment of individuals diagnosed with metastatic or treatment-refractory DTC are currently underway. The objective of this review is to evaluate recent clinical trials that have studied novel targeted drugs for treatment of DTC.