肿瘤相关成纤维细胞在胰腺癌发生发展中的研究进展

胰腺癌是致命的恶性肿瘤之一,由于缺乏早期、敏感及特异性的诊断标志物,大多数患者确诊时已处于晚期。胰腺癌又称硬癌,其肿瘤组织中含有大量的间质成分,广泛的纤维化是胰腺癌的重要特征。肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)是肿瘤微环境中重要的组成成分,研究表明CAFs参与胰腺癌细胞增殖、迁移、侵袭、耐药等生物学过程。全文主要介绍胰腺癌中CAFs的异质性及其在胰腺癌发生发展中的作用,并阐述了类器官培养技术在CAFs研究中的应用,以及靶向CAFs进行肿瘤治疗的进展。     

肿瘤的内科治疗新策略北大核心CSCD

传统的肿瘤治疗策略是寻找和消灭肿瘤。当肿瘤治疗进入精准治疗时代,肿瘤的治疗策略也转变为靶向、控制、调变和重构,即通过精确的靶向治疗,控制肿瘤的复制、血管生成以及侵袭和转移,调变肿瘤细胞进入凋亡或休眠状态,同时重构新的结构、微环境和代谢体系。治疗策略的新转变无疑将提高肿瘤患者的临床获益。     

CAFs在胰腺癌肿瘤微环境中作用的研究进展

胰腺癌肿瘤微环境中癌相关成纤维细胞（cancer-associated fibroblasts,CAFs）具有促进胰腺癌组织增殖、侵袭、转移、血管生成、免疫抑制及耐药等作用,在胰腺癌的演变和进展中发挥了重要作用。由于CAFs的起源较多且具有表型和功能异质性,给靶向CAFs的抗肿瘤治疗带来了巨大挑战,但是探究CAFs与胰腺癌细胞的相互作用可以为日后靶向CAFs治疗胰腺癌提供帮助。本文将探究胰腺癌肿瘤微环境中CAFs的作用机制并对近些年来国内外有关CAFs对胰腺癌作用的相关文献进行综述。     

精准医疗背景下晚期恶性黑色素瘤治疗的现状与进展

恶性黑色素瘤过去一直以手术切除和药物化疗为主要治疗手段,预后不佳。随着高通量基因测序技术的发展和对肿瘤分子机制认识的加深,人们发现肿瘤异质性和肿瘤微环境多样性影响了肿瘤的形成、耐药和治疗选择,导致了黑色素瘤患者对同种治疗方法的反应和获益不同。靶向治疗和免疫治疗的出现与进展,黑色素瘤患者的生存率显著上升,推动了黑色素瘤治疗的个体化与精准化,促使精准医疗成为研究的热点与趋势。本文旨在总结建立在精准分型和分子水平上的晚期黑色素瘤个体化综合治疗的研究进展,阐述精准医疗时代背景下黑色素瘤患者的生存现状,以及发展多种靶向治疗、免疫治疗或联合疗法的前景与必要性。     

胰腺癌免疫治疗研究进展

胰腺癌作为一种致命的恶性肿瘤，起病隐匿，对放化疗、靶向治疗等传统治疗不敏感，患者预后极差。免疫治疗是当今多种恶性肿瘤综合治疗的有效手段，以其显著临床疗效而备受瞩目。然而胰腺癌因其较低的肿瘤免疫原性和独特的肿瘤微环境在免疫治疗迅速发展的当今成为难以攻破的一方“免疫荒漠”。目前胰腺癌免疫治疗的研究方向主要包括：肿瘤疫苗、免疫检查点抑制剂、单克隆抗体、溶瘤病毒、T细胞治疗等。本文将对以上相关研究进展作一综述，以期为胰腺癌的免疫治疗提供新思路。     

肿瘤微环境与免疫治疗耐药的关系及应对

免疫治疗的革命性进展开创了肿瘤精准化治疗的新时代，为肿瘤患者带来了长期生存获益。然而，在临床实践中仍存在免疫治疗耐药等诸多挑战。肿瘤微环境（tumor microenvironment,TME）的动态抑制性变化、异质性等特点在肿瘤发生发展、恶性进展、免疫逃逸和治疗耐药中发挥重要作用。因此，了解免疫治疗与TME之间的相互作用不仅对剖析其作用机制至关重要，而且有助于为提高免疫治疗疗效提供新的途径。本综述就TME的起源、动态抑制性变化、异质性特点进行总结，介绍关于TME如何影响免疫疗效的研究进展，以期通过靶向TME角度或联合治疗方式寻求优化免疫治疗疗效的应对策略。     

晚期胰腺癌的分子治疗研究现状

胰腺癌是全球第七大致命的恶性肿瘤，分别是美国胃肠道恶性肿瘤和癌症相关死亡的第二大和第三大原因。与其他恶性肿瘤相比，晚期胰腺癌患者的生存率最低，中位总体生存率为2~8个月，5年生存率为8.5%。治疗十分困难，给临床医生带来极大挑战。目前晚期胰腺癌的治疗药物匮乏，化疗仍然是其主要治疗方法。虽然化疗能短暂的控制疾病的进展，但是在生存期的延长方面却差强人意。分子靶向治疗已在其他的瘤种中取得了里程碑般的成就，譬如肺癌、结直肠癌等，但晚期胰腺癌患者的分子靶向治疗效果并不显著。这需要我们去寻找新的治疗靶点和药物。本文基于胰腺癌信号传导通路及肿瘤微环境，总结和分析晚期胰腺癌分子治疗的研究现状，探索未来胰腺癌治疗的发展方向。     

可切除胰腺癌的围手术期治疗与全程管理

胰腺癌是恶性程度和致死率极高的消化道恶性肿瘤。可切除胰腺癌是指可以通过手术达到根治性切除的胰腺癌，临床研究表明辅助化疗能延长可切除胰腺癌患者的生存期，但总体预后仍不乐观。目前国内缺乏一套规范的可切除胰腺癌患者全程管理模式。本文通过对可切除胰腺癌近20年来辅助治疗、新辅助治疗、分子靶向治疗、靶向肿瘤微环境的治疗如免疫治疗和肿瘤疫苗、特殊类型可切除胰腺癌的治疗进展进行综述，以期为临床医生对可切除胰腺癌患者的全程管理提供参考。      

靶向TROP2在胰腺癌治疗中的潜力

胰腺癌是发病率高、进展速度快且生存率低的一种恶性肿瘤,临床上亟待寻找可用于精准治疗或提高预后的新靶标。近年来研究发现,滋养层细胞表面抗原2（trophoblast cell surface antigen 2,TROP2）在多种恶性肿瘤中高表达,通过细胞表面受体信号参与恶性肿瘤细胞的增殖、迁移及黏附等进展过程。概述TROP2在胰腺癌中的表达、参与介导的信号转导通路及以TROP2为靶点的抗肿瘤药物的研究进展,为靶向TROP2在胰腺癌治疗中的机制和提高胰腺癌患者预后方面提供参考。     

纳米材料在肿瘤免疫治疗中的应用

肿瘤免疫治疗是一种通过增强自身免疫应答来治疗肿瘤的新兴策略,能够防止肿瘤的转移和复发。然而,由于肿瘤的复杂性、患者的异质性及肿瘤免疫抑制微环境等问题的存在,导致免疫治疗整体有效率仅20%左右。近年来,纳米材料以其良好的生物相容性、靶向性和可控释放等优势,在肿瘤免疫治疗领域受到了越来越广泛的关注。纳米材料能够赋予免疫刺激分子、治疗药物等靶向肿瘤的能力,增强肿瘤部位药物的聚集,达到局部免疫调节,改善免疫抑制微环境,提高肿瘤免疫治疗的效果。本文就目前免疫治疗的现状及多种纳米材料在提高免疫治疗效果中的研究进展进行综述。     

Novel therapies targeting hypoxia mechanism to treat pancreatic cancer

Pancreatic cancer (PC) is one of the deadliest malignancies. The high mortality rate of PC largely results from delayed diagnosis and early metastasis. Therefore, identifying novel treatment targets for patients with PC is urgently required to improve survival rates. A major barrier to successful treatment of PC is the presence of a hypoxic tumor microenvironment, which is associated with poor prognosis, treatment resistance, increased invasion and metastasis. Recent studies have identified a number of novel molecules and pathways in PC cells that promote cancer cells progression under hypoxic conditions, which may provide new therapy strategies to inhibit the development and metastasis of PC. This review summarizes the latest research of hypoxia in PC and provides an overview of how the current therapies have the capacity to overcome hypoxia and improve PC patient treatment. These findings will eventually provide guidance for future PC management and clinical trials and hopefully improve the survival of patients with PC.     

Current perspectives in the treatment of advanced prostate cancer

Prostate cancer (PC) continues to be an important world health problem for men. Patients with locally confined PC are treated with either radiotherapy or surgery. However, treatment of more advanced stages of the disease is problematic. Initially, androgen deprivation offers a period of clinical stability, which is however invariably followed by progression to non-responsiveness to hormonal manipulation. Current management of patients with androgen-independent prostate cancer (AIPC) displays modest response rates and achieves only short-term benefit. Recently, knowledge in the complex pathophysiology of advanced PC has led to the identification of mechanisms and target molecules permitting the introduction of new therapies. Consequently, many investigational treatments are ongoing for AIPC in Phase-II and Phase-III trials aiming at the combination of chemotherapeutic regimens along with immunotherapy targeting PC-associated antigens. Other attractive options are gene therapy, as well as the targeting of survival signaling, differentiation, and apoptosis of the malignant PC cells. Further treatment modalities are directed against the tumor microenvironment, bone metastasis, or both. Collectively, the aforementioned efforts introduce a new era in the management of advanced PC. Novel pharmaceutical compounds and innovative approaches, integrated into the concept of individualized therapy will hopefully, during the next decade, improve the outcome and survival for hundreds of thousands of men worldwide.     

Targeting the microenvironment of pancreatic cancer: overcoming treatment barriers and improving local immune responses

Historically, patients diagnosed with metastatic pancreatic cancer have faced a grim prognosis. The survival benefit seen with systemic chemotherapies and even combinations thereof have been disappointing. However, growing data suggest that the microenvironment of pancreatic cancer may be contributing to this poor prognosis. This microenvironment has a dense fibrotic stroma, and is hypoxic and highly immunosuppressive, all of which pose barriers to treatment. Newer strategies looking to disrupt the fibrotic stroma, target hypoxic areas, and improve local immune responses in the tumor microenvironment are currently undergoing clinical evaluation and seem to offer great promise. In addition to these therapies, preclinical work evaluating novel cytotoxic agents including nanoparticles has also been encouraging. While much research still needs to be done, these strategies offer new hope for patients with pancreatic cancer.     

Therapeutic exploitation of the physiological and molecular genetic alterations in head and neck cancer.

Despite improvements in the diagnosis and management of head and neck squamous cell carcinomas, there has been minimal increase in the long-term survival in these patients over the last 30 years. Treatment intensification with concurrent chemoradiotherapy has been shown to increase survival and improve organ preservation over radiotherapy alone in patients with locally advanced tumor; however, at a cost of increased long-term toxicity. Recent advances in molecular technology have ushered in a new age of targeted therapy, which holds promise for a better outcome for these patients with potentially less normal tissue toxicity. Some of the new approaches aim to specifically inhibit tumor growth and metastasis by targeting the tumor microenvironment or vasculature, whereas others focus on specific protein or signal transduction pathways. This review will summarize these new molecular and physiological based strategies that can be used for both treatment and chemoprevention of head and neck squamous cell carcinoma.     

Autophagy Inhibition in Pancreatic Adenocarcinoma

Although some progress has been made in recent years with the development of more effective chemotherapy regimens, new treatment approaches are needed to improve outcomes for patients with pancreatic adenocarcinoma. The cellular process of autophagy, a cell survival mechanism that allows cancer cells to survive the hazardous conditions of the tumor microenvironment and treatment, has emerged as a viable target in pancreatic cancer. We review the mechanism of autophagy, its role in pancreatic carcinogenesis, the preclinical and clinical evidence supporting targeting autophagy in patients with pancreatic adenocarcinoma, and areas of future investigation that hold promise for improving this treatment approach.     

放疗联合免疫检查点抑制剂在胶质母细胞瘤治疗中的研究进展

胶质瘤是颅内最常见的原发性肿瘤,大部分患者表现为胶质母细胞瘤,发病率及致死率极高。尽管胶质母细胞瘤患者经过手术切除联合放、化疗的标准化治疗,但预后仍然很差。近年来,免疫治疗在多种实体肿瘤治疗中取得了突破性进展,但现有数据显示免疫治疗对提高胶质母细胞瘤患者生存期的效果不佳。然而研究表明,免疫治疗可以与放疗产生协同效应,放疗可以增加抗原呈递,并促进促炎性肿瘤微环境的形成,为免疫治疗提供更多相关靶点。本文旨在讨论放疗对肿瘤免疫微环境的影响,以及放疗联合免疫检查点抑制剂在胶质母细胞瘤治疗中的作用。     

Integrating tumor‐initiating cells into the paradigm for melanoma targeted therapy

There is growing evidence to suggest that not all cancer cells have similar levels of malignant potential and that tumor progression may be driven by specialized sub‐sets of “tumor initiating” cells. It is likely that as tumor initiating cells have lower proliferation rates and enhanced survival mechanisms they may also drive drug resistance. Melanoma is known to be an exceptionally therapy resistant tumor, with no treatment yet identified to alter the natural progression of the disseminated disease. In the current review, we discuss evidence for the existence of melanoma initiating cells and described possible therapeutic strategies to eradicate this population via the targeting of specific cell‐surface markers or through the disruption of the interaction of the melanoma initiating cells with their local microenvironment. It is hoped that the targeting of melanoma initiating cells may be one approach to overcome the incredible therapy resistance of this tumor. © 2008 Wiley‐Liss, Inc.     

Chemotherapy for non-small-cell lung cancer. Part 2: Advanced disease

The prognosis of patients with advanced non-small-cell lung cancer (NSCLC) remains poor. Systemic chemotherapy prolongs survival in this group of patients and palliates symptoms compared to best supportive care alone but more effective therapeutic strategies are needed. Novel agents that selectively target biological pathways of tumor growth offer hope of improving response and survival rates beyond what has been achieved with standard cytotoxic chemotherapy. Part 2 of this two-part article addresses the role of chemotherapy in locally advanced and advanced NSCLC, including the use of novel agents, considerations in elderly patients, and studies of second-line treatment.