肾细胞癌治疗药物的研发进展

肾细胞癌(renal cell carcinoma, RCC)是一种致命的恶性肿瘤,其治疗方式包括手术切除、靶向治疗、免疫治疗和联合治疗等。近年来,随着分子生物学和药物研发技术的不断发展,肾细胞癌的药物治疗取得了长足的进展,包括靶向治疗药物的不断更新、免疫治疗的革命性突破以及联合治疗的策略优化。该文将对肾细胞癌的靶向治疗、免疫治疗以及联合治疗进行系统综述。     

肾细胞癌免疫治疗的研究进展

肾细胞癌（renal cell carcinoma, RCC）是成年男性常见的恶性肿瘤, 其发病率和死亡率排名均较前。免疫治疗能够激活机体免疫系统产生对肿瘤的反应使疾病稳定,但高剂量不良反应限制了其在临床的广泛应用。而靶向药物的兴起让肾癌患者治疗方式向靶向治疗转变。随着对肾癌临床治疗方式的不断深入研究,发现单纯的免疫或靶向治疗难以得到令人满意的疗效。因此有学者提出肾细胞癌的治疗应该向免疫联合靶向治疗方向转变。本文旨在对当前肾细胞癌相关免疫治疗的临床研究作一综述,以期为临床肾细胞癌的免疫治疗提供一定的理论依据。     

基于生物学行为的晚期胆管癌靶向免疫治疗进展

胆管细胞癌（cholangiocarcinoma，CCA，简称胆管癌）是一种起源于胆管上皮细胞且具有高度异质性的胆道恶性肿瘤。早期症状不明显，发现时多为晚期。晚期CCA恶性程度高，目前一线化疗疗效有限，预后差。近年来，随着测序技术的发展，对不同亚型CCA的基因组和转录组特征有了更深的认识，也为CCA靶向治疗和免疫治疗奠定基础。近期随着Pemigatinib被FDA批准用于FGFR2基因融合或其他重排类型的晚期经治CCA，以及帕博利珠单抗被批准用于微卫星不稳定性高（microsatellite instability-high，MSI-H）或 DNA错配修复缺陷（different mismatch repair，dMMR）晚期实体瘤，免疫靶向药物治疗晚期CCA随之成为新的研究方向。本综述将结合CCA的生物学特征，总结当前靶向治疗和免疫治疗在CCA中的应用现状。     

晚期肝细胞癌的系统治疗现状及研究进展

摘 要：肝细胞癌（hepatocellular carcinoma，HCC），是一种发病率和死亡率高、预后差且易复发和转移的消化系统恶性肿瘤。以靶向治疗和免疫治疗为主的系统治疗在晚期HCC一线治疗中疗效肯定。靶向治疗联合免疫治疗可有效延长患者生存期，改善预后，中药辅助治疗也在综合抗肿瘤治疗中发挥作用。病因治疗和新的抗HCC作用靶点也是肝细胞癌领域的研究热点。全文主要围绕晚期HCC的靶向治疗、免疫治疗等系统治疗以及病因和新作用靶点研究的现状及进展进行综述。     

肺鳞状细胞癌靶向治疗研究进展

肺鳞状细胞癌是肺癌的主要组织学类型之一。与肺腺癌不同,肺鳞状细胞癌患者从靶向治疗中的获益有限。虽然免疫治疗显著改善了肺鳞状细胞癌患者的预后,但是相对较低的有效率和相关不良反应限制了免疫治疗在肺鳞状细胞癌患者中的应用。肺鳞状细胞癌的发生与发展过程中存在多种基因突变,随着分子生物学、表观遗传学和代谢组学的进一步发展,针对肺鳞状细胞癌的发病过程相关信号通路的研究也在不断进行,目前临床也对一些治疗靶点进行了相关研究。了解肺鳞状细胞癌的发病机制以及不同信号通路之间的内在联系对靶向药物的研发至关重要。本文主要对表皮生长因子受体（epidermal growth factor receptor,EGFR）通路、血管内皮生长因子（vascular endothelial growth factor,VEGF）/血管内皮生长因子受体（vascular endothelial growth factor receptor,VEGFR）、磷脂酰肌醇3激酶（phosphoinositide3-kinase,PI3K）信号通路和周期蛋白依赖性激酶（cyclin-dependent kinase,CDK）4/6等...     

肝内胆管细胞癌免疫治疗和靶向治疗研究现状

肝内胆管细胞癌（intrahepatic cholangiocarcinoma，ICC）是发病率第二的原发性肝癌。由于其恶性程度高，转移扩散早，患者多因黄疸或周围压迫不适感前来就医，使其确诊较晚。且ICC切除后易复发，对化疗不敏感，故预后差，生存率低。目前对于能手术切除的ICC患者采取以手术为主的多学科综合治疗，对于无法手术切除的晚期ICC患者采取以局部治疗联合化疗为主的综合治疗。免疫治疗可利用自身免疫系统清除肿瘤细胞，分子靶向治疗可通过抑制对肿瘤发生发展有促进作用的细胞膜表面分子而杀死肿瘤细胞。目前，这两种治疗方法已成为ICC治疗的研究热点，本文就其研究现状进行综述。      

晚期肾癌的抗血管内皮生长因子靶向治疗

晚期肾癌预后差而且对放化疗抗拒，免疫治疗仅使极少部分患者受益。血管内皮生长因子（VEGF）在肾透明细胞癌过量表达，表明它可以作为一个新的靶向治疗途径。经过临床试验证实，以VEGF为靶向通路的药物在治疗肾癌方面取得令人鼓舞的效果。     

头颈部鳞状细胞癌的肿瘤微环境及免疫治疗研究进展

头颈部鳞状细胞癌（HNSCC）是最常见的一类异质性恶性肿瘤。超过60%的HNSCC患者在确诊时已处在肿瘤晚期 或转移阶段，针对复发性或转移性HNSCC（R/MHNSCC）患者可选择的治疗方式及其疗效有限。肿瘤免疫治疗是治疗HNSCC的 重要手段之一，尽管免疫治疗持久的反应率较高，但目前只有很低比例的HNSCC患者作出反应，临床上仍存在免疫治疗耐药等 挑战。HNSCC肿瘤微环境（TME）的生物学特征、动态抑制性变化和异质性等特点，在HNSCC的发生与发展、免疫逃逸和治疗耐 药中起重要的作用。在综述中，论述了抗肿瘤免疫细胞以及细胞外成分在HNSCC的TME中的作用及其机制，总结了HNSCC相 关免疫治疗策略，并展望了免疫治疗与放射或化学治疗等传统肿瘤治疗方式组合提高HNSCC个体精准化免疫治疗的疗效。     

小细胞肺癌脑转移治疗进展

肺癌是呼吸系统发病率、死亡率最高的恶性肿瘤,小细胞肺癌属于神经内分泌癌,侵袭性强、恶性程度高,易发生脑转移,严重影响患者生活质量及生存期。小细胞肺癌脑转移治疗方式有手术、化疗、放疗、靶向治疗和免疫治疗,治疗措施多,治疗效果差异大。随着各种诊断、治疗措施进展,小细胞肺癌脑转移治疗效果较前明显改善,对不同患者如何选择个体精准有效的临床治疗措施,延长脑转移患者生存时间,提高生活质量,是目前研究的热点之一。     

肾细胞癌靶向治疗研究现状

肾细胞癌被认为是最难治的恶性肿瘤之一。由于对肾细胞癌分子发病机制研究的进一步深入，在晚期肾细胞的治疗中出现了一系列成功范例。在过去20年，非特异性免疫治疗被认为是晚期肾细胞癌治疗标准。近年，随着分子靶向药物的研发和临床使用，肿瘤的分子靶向治疗已成为肿瘤治疗的研究热点，同时由于对肾细胞癌进一步了解，肾细胞癌的治疗已开始转向抗-血管内皮生长因子及其相关通路研究，大量的临床研究试验，证明了分子靶向治疗在晚期肾细胞癌的疗效，其中Sorafenib（索拉非尼）和Sunitinib（舒尼替尼）分别于2005年和2006年经美国FDA批准用于晚期肾细胞癌。本文将围绕VEGF在肾细胞癌的重要性和Bevacizumab（贝伐单抗）、Sunitinib和Sorafenib治疗晚期肾细胞癌研究进展等问题进行简要阐述。     

光动力联合治疗在不可切除肝外胆管癌中的应用进展

胆管癌是起源于胆管上皮的恶性肿瘤,发病率逐年升高,其早期症状不典型,诊断率低,就诊时大多已是晚期,失去最佳的手术时期。目前对于不可切除性肝外胆管癌的保守治疗方法有支架置入、射频消融、放疗和化疗、靶向、免疫治疗等,但由于胆道肿瘤恶性程度高,易产生耐药,且新兴治疗方式的获益人群有限,因此我们亟需探索新的治疗策略来突破此瓶颈。光动力疗法作为一种治疗胆管癌的新手段,其临床应用效果引起广泛关注。本文主要针对光动力治疗原理、光动力与其他治疗方式的联合使用,尤其是光动力联合新兴的免疫和靶向治疗进行归纳总结,并阐述目前国内外光动力治疗研究的热点方向,为临床及科研提供参考。     

靶向治疗对多发性骨髓瘤患者疗效及生存的影响

目的 探讨分子靶向治疗（沙利度胺、来那度胺或硼替佐米）对多发性骨髓瘤（MM）患者疗效及生存的影响.方法 回顾性分析217例自1989年至2013年上海交通大学附属第一人民医院血液科收治的MM患者治疗情况,对比不同时期诊治患者的生存情况,分析治疗措施的改进对患者疗效及生存的影响.结果 基于靶向治疗的普及从1998年后开始,1998年之后确诊的MM患者较之前确诊患者的生存期有显著改善.共有75例患者在初始治疗中接受了沙利度胺或硼替佐米治疗,其疗效优于接受MP、VAD等传统方案的患者.在复发、进展阶段中接受靶向治疗的患者有49例,其疗效较传统方案占优.共有16例患者接受了自体或异基因造血干细胞移植,其中接受自体及异基因双移植的有4例,其疗效及生存期较其他未接受移植治疗的患者占优.结论 分子靶向治疗的应用提高了MM的疗效,并进一步使患者的生存时间得到延长.     

甲磺酸阿帕替尼治疗恶性肿瘤的临床不良反应分析

抗血管生成在恶性肿瘤治疗中的作用日益突出，其在转化、维持治疗过程中都发挥重要作用。我国自主研发的抗血管生成靶向药甲磺酸阿帕替尼（apatinib，YN968D1）已批准用于晚期胃腺癌或胃-食管结合部腺癌的三线及三线以上的治疗，并在多个实体肿瘤中探索应用。随着对阿帕替尼研究的深入，其安全性问题受到广泛关注。本文重点介绍了阿帕替尼在临床应用中常见的不良反应，综合分析了现有的临床数据，对比了阿帕替尼与其他常用抗血管生成药物不良反应的优劣，以期帮助临床医生更好地把握该药的安全性，从而为患者提供更加安全、有效的治疗。      

肝内胆管细胞癌的治疗进展

肝内胆管细胞癌(ICC)当前首选治疗手段仍为手术治疗.吉西他滨联合顺铂全身化疗方案可推荐为不可切除ICC患者的标准治疗方案.近年来新辅助治疗联合肝移植方案的提出为肝移植治疗ICC开拓了新的治疗前景.此外,放疗、介入治疗、射频消融治疗、分子靶向治疗等也是综合治疗ICC的重要组成部分.     

The role of interventional radiology in the treatment of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma. Complete surgical resection remains the only potentially curative option for patients with ICC. However, until now, early diagnosis with potential surgical intervention has been the exception rather than the rule with only 30% of patients qualifying for attempted surgical cure. Many patients are unresectable because of disease stage, anatomic conditions, medical comorbidities, and small future remnant liver. Interventional radiology procedures are available for these types of patients with intra-arterial therapies and/or ablative treatments both for curative and for palliative treatment. The goals of interventional therapy are to control local tumor growth, to relieve symptoms, and to improve and preserve quality of life. The choice of treatment depends largely on tumor extent and patient performance. No randomized studies exist to compare treatments. The present review describes the current evidence of the interventional treatments in the management of the ICC. Moreover, interventional procedures available to increase the future liver reserve before surgery were analyzed.     

晚期雌激素受体阳性乳腺癌的治疗进展

针对晚期雌激素受体阳性乳腺癌虽然主要使用内分泌、靶向等治疗方法，但内分泌治疗的耐药问题在临床上较常见。随着对CDK4/6、PI3K-Akt1-mTOR通路等治疗靶点和耐药机制的研究，晚期雌激素受体阳性乳腺癌的靶向治疗已成为研究热点，利用基因靶向治疗等也可能成为新的突破点，同时在如何针对不同患者选择最佳治疗方案、最佳治疗时间等问题上仍存在挑战。本文将就晚期雌激素受体阳性乳腺癌的治疗进展进行综述。      

Treatment of metastatic breast cancer: looking towards the future

The armamentarium for the treatment of metastatic breast cancer is increasing with the introduction of newer chemotherapeutic agents and the development of molecular targeted therapies. The clinical utility of anthracyclines in advanced breast cancer has been limited by significant adverse events; therefore the taxanes are increasingly used in the metastatic setting. Trastuzumab with a taxane as first-line therapy is now standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Other targeted therapies, including the antiangiogenesis agents such as bevacizumab, are being investigated both as monotherapy and in combination regimens. While the number of available agents is growing rapidly, challenges remain concerning appropriate dose, schedule, treatment duration and management of drug resistance. This paper reviews recent data regarding the established and investigational medical treatments for endocrine-refractory metastatic breast cancer, and presents treatment recommendations.     

Recent advances in the treatment of prostate cancer

As new evidence for prostate cancer treatment has emerged in the last few years, longstanding controversies in the treatment of prostate cancer have resurfaced. A number of long-held tenets of prostate cancer therapy have been revisited, sometimes with surprising and challenging results. Although neoadjuvant hormonal therapy prior to radical prostatectomy decreases positive surgical margin rates, longer follow-up is needed to support survival improvement of this combined modality therapy. Androgen deprivation combined with radiation therapy appears to improve disease-free survival (and survival in one series) in patients with locally advanced cancer. Another approach to locally advanced prostate cancer using three-dimensional conformal radiation therapy may improve long term outcome. The data are currently insufficient to conclude that interstitial low dose rate brachytherapy is equivalent to conventional treatments: patients with small tumor volumes and low Gleason grade seem to obtain more benefit, whereas for large tumors with higher gleason grades this approach seems inferior to conventional treatments. In advanced prostate cancer recent data suggest that immediate hormonal therapy improves survival. In this group of patients the use of maximum androgen blockade remains controversial but may adversely affect quality of life compared to orchiectomy alone. Intermittent hormonal therapy may improve quality of life, although effect upon survival is unknown. Chemotherapy in combination with androgen deprivation is currently being studied as front-line therapy in advanced prostate cancer. Palliative benefit of chemotherapy for hormone refractory prostate cancer remains an important endpoint; survival advantage has not been seen in any randomized trials. Suramin may delay disease progression in hormone refractory prostate cancer. Many aspects of prostate cancer treatment will remain controversial until results of large, randomized trials with longer follow-up are available.     

The Wide Experience of the Sequential Therapy for Patients with Metastatic Renal Cell Carcinoma

Sequential targeted therapies are the standard of care for patients with metastatic renal cell carcinoma (mRCC). Several drugs are available for patients whose disease progresses while they receive initial tyrosine kinase inhibitor (TKI) therapy; these include nivolumab (an inhibitor of PD-1 receptor), everolimus (an inhibitor of the mechanistic target of rapamycin) or additional TKIs. Until now, there has been no clinical evidence to support the use of one strategy versus another, so investigators and physicians rely on experience, judgement and findings from molecular analyses to select the appropriate treatment. However, with the arrival of nivolumab and cabozantinib that provide an overall survival higher than other alternative treatments, therapeutic strategies may have changed. Here, we discuss findings from preclinical and clinical studies that might help clinicians to choose the optimal treatment approach for patients with mRCC who progress to initial therapy.     

Biology and management of malignant pleural mesothelioma

Malignant mesothelioma is an aggressive tumour, with a poor prognosis and an increasing incidence as a result of widespread exposure to asbestos. The results of the treatments available are poor. Surgery and radiotherapy have a limited role in highly selected patients and systemic therapy is the only potential treatment option for the majority of patients. Despite some definite activity of the novel antifolates such as pemetrexed and raltitrexed, the results, even in combination with platinating agents, are still modest, with a median survival of approximately one year. The better understanding of the biology of mesothelioma makes the assessment of a number of targeted agents particularly interesting. Unfortunately, the targeted agents imatinib, gefitinib, erlotinib and thalidomide have been shown to be ineffective in unselected patients. Studies with anti-angiogenesis agents are ongoing. An improvement of the knowledge of major molecular pathways involved in malignant mesothelioma is needed in order to define proper targets for the systemic treatment of this disease.