c-Met靶向成像在肿瘤诊断中的应用

肝细胞生长因子受体(c-Met)是一种酪氨酸激酶型受体,对于肿瘤的发生发展至关重要,c-Met靶向治疗已初步应用于临床,其对于癌症患者的治疗具有显著的益处。目前,由于无法对c-Met表达阳性的肿瘤患者进行有效的早期筛选,使得c-Met靶向治疗在肿瘤治疗中总体有效率偏低。c-Met靶向分子成像借助靶向分子成像探针能够实现肿瘤c-Met表达水平及活化状态的定量检测和直观揭示,对于肿瘤的早期诊断、治疗和预后具有重要意义和巨大的潜在价值。结合近年来c-Met靶向分子成像的研究,本文将深入分析、探讨c-Met靶向分子成像探针的构建及其在肿瘤诊断中的应用。     

Kruppel样转录因子4在恶性肿瘤中的作用及其在乳腺癌中的表达

随着乳腺癌发病率的逐年上升,找寻能评估乳腺癌风险、预测乳腺癌预后及提供乳腺癌靶向治疗意义的新型乳腺癌分子标志物至关重要。近年来Kruppel样转录因子4（Kruppel-like factors 4,KLF4）是否可以作为乳腺癌分子标志物成为研究的热点。KLF4主要参与细胞的周期调控、凋亡、代谢及干细胞自我更新等过程,在肿瘤中既表现促癌的作用也表现抑癌的机制,尤其在乳腺癌中颇受争议。本文通过总结归纳KLF4因子在不同肿瘤中的表达及作用,尤其在乳腺癌中可能存在的促癌、抑癌机制及其表达情况,发现KLF4具有乳腺癌预后及成为新型分子靶向治疗靶点的潜力。     

头颈部恶性肿瘤的靶向治疗进展

手术和放疗技术的进步对局部晚期或晚期头颈部肿瘤患者并未带来长期生存率的明显提高,靶向治疗日渐成为包括头颈部肿瘤在内的重要治疗选择。表皮生长因子受体在头颈部肿瘤中有较高水平表达,其表达情况与疾病的预后密切相关,并成为靶向治疗的重要靶点。针对该受体的抑制剂在头颈部肿瘤中应用取得了令人满意的疗效,目前临床资料显示该类药物单药及与其它治疗手段的联合在头颈部肿瘤中应用均取得较好疗效,但是靶向药物的作用机制及其敏感性的预测分子尚不明确。针对复发转移的头颈部肿瘤的二线治疗的Ⅲ期临床正在进行,与其他治疗手段的联合治疗的方法正在探索和验证,新的预测分子也在涌现。本文将对以上内容进行综述。     

基于分子影像的非小细胞肺癌分子靶向治疗及免疫治疗进展

我国癌症发病率与死亡率中肺癌均高居第一位，其中非小细胞肺癌（NSCLC）占肺癌85%以上， NSCLC传统治疗方式包括手术、化疗、放疗等。近十几年来，NSCLC相关临床治疗取得巨大突破，代表性治疗新方案即为分子靶向治疗和免疫治疗，然而，上述治疗方式成功发挥治疗作用前提和关键则是精准选择NSCLC患者治疗优势人群。分子影像可以在活体状态下，应用影像学方法对人或动物体内细胞和分子水平生物学过程进行成像、定性和定量研究，着眼于生物过程基础变化而不是生物变化最终结果，进而实现精准选择治疗优势人群、分子水平精准监测治疗效果、及时进行预后评估等目的，对分子靶向治疗以及免疫治疗意义重大。该文综述分子影像在NSCLC分子靶向治疗以及免疫治疗中开展的相关研究。     

分子检测与肿瘤靶向治疗

近年来,随着人们对肿瘤发病机制的进一步认识,以及对肿瘤细胞信号通路研究的深入,开始了以细胞受体、关键基因和调控分子为靶点的治疗,并称之为“靶向治疗”,然而靶点分子的基因多态性决定了靶向药物治疗的有效性。文章概述肿瘤靶向治疗中基因多态性检测的意义。     

以间皮素为靶点的肿瘤特异性核素成像研究进展

间皮素（mesothelin, MSLN）是多种肿瘤表面特异性表达的受体蛋白,特别是在以胰腺癌（80%~85%）为首的多种实体肿瘤中高表达,而在正常组织中间皮素的表达仅局限于胸膜、心包膜和腹膜中。通过新型核素标记抗MSLN抗体,可以对多种肿瘤进行特异性成像,对肿瘤早期诊断及预后评价起到重要的作用。本综述以间皮素为靶点,阐述与该靶点相关的胰腺癌等相关肿瘤间皮素靶点诊疗的重要进展,并重点阐述了核素标记的具有MSLN特异性的分子探针在肿瘤临床核素成像中的最新研究进展。     

HER2、EGFR信号通路与胃癌的靶向治疗

随着肿瘤分子生物学的发展,尤其是对肿瘤细胞增殖生长和转移过程中的信号转导通路作用机制研究的不断深入,继而为其特异性靶点而设计的分子靶向药物的开发,使肿瘤治疗已经进入了一个全新的时代。酪氨酸激酶受体HER家族中的HER2和EGFR在许多肿瘤中的过表达和（或）突变与许多肿瘤发生发展及预后密切相关,而以HER2和EGFR为靶向的胃癌治疗和针对其信号转导通路的信号转导干预治疗又备受关注。     

乳腺癌分子靶向治疗进展、困境和出路

乳腺癌是一种复杂的异质性疾病。近年来,随着分子生物学技术的飞速发展,从分子水平认识肿瘤的发生、发展机制,已经越来越深入、透彻。针对细胞受体、关键基因和调控分子为靶点的治疗,即靶向治疗在临床应用也愈来愈广泛。     

乳腺癌靶分子间相互作用

正随着肿瘤靶向治疗时代的到来,乳腺癌靶分子成为研究热点,同时对靶分子的深入研究也推动了乳腺癌靶向治疗的发展,改善了乳腺癌患者的预后但是在临床实际应用中,仍然存在针对单个特异性分子靶点的靶向药物治疗无效;或者在初始有效的患者中,继发耐药现象。由于乳腺癌的分子异质性,对于靶分子间的相互作用机制仍缺乏系统认识,因此限制了临床靶向治疗的发展。在众多靶分子相     

肝癌的分子靶向治疗研究进展

不能手术和已转移的原发性肝细胞癌预后很差,放化疗难以使患者受益。近年来,分子靶向治疗对一些肿瘤已取得突破性进展,肝癌的分子靶向治疗也在临床试验中取得了令人鼓舞的结果。目前的肝癌临床研究主要针对EGFR、VEGF/VEGFR、Raf/MAPK-ERK、HGF、乙肝表面抗原等靶点。本文针对肝癌的分子靶向治疗的研究进展进行了综述。     

从分子水平认识和治疗胶质瘤

胶质瘤是神经系统最常见的原发性肿瘤，临床预后还不乐观。我们在临床工作中注意到即使是相同病理类型和级别的胶质瘤，治疗效果存在很大差异。治疗上的差异无疑是重要影响因素，但肿瘤内在的生物学特性，特别是分子水平的差异是关键所在。近年来．神经胶质瘤的诊断和治疗已深入到了分子水平。影像学诊断已不单纯解剖定位，还可以提供分子和功能影像参考：胶质瘤的病理诊断也在组织学分型/分级的基础上进行分子病理分类，并以此为个体化治疗提供参考；治疗开始从传统的手术/放疗/化疗深化到了分子靶向治疗。随着对胶质瘤分子病因/病理机制的深入了解，胶质瘤的临床治疗效果将会进一步提高。     

Molekulare Bildgebung in der Tumortherapie

Targeted drugs that modulate the function of specific molecules in diseased tissues hold great promise for the treatment of many diseases, including malignant tumors. However, there are several challenges for the efficient evaluation of these drugs in clinical trials as well as for the use in clinical practice. These include (i) the selection of patients likely to benefit from treatment with a specific targeted drug, (ii) finding the right dose and dose schedule, (iii) monitoring target inhibition, and (iv) assessing tumor response to therapy. Standard anatomic imaging continues to play an important role for addressing these challenges, but molecular imaging provides several new opportunities to make the use of targeted drugs more efficient. Using molecular imaging, the expression of drug targets can be assessed noninvasively, the concentration of drugs can be measured in the tumor tissue, target inhibition can be monitored, and tumor response to therapy can be evaluated earlier than with anatomic imaging techniques. Therefore, it is expected that molecular imaging will play an increasing role for guiding molecularly defined therapeutic interventions.     

放射性核素分子成像在肿瘤精准诊疗中的临床应用

肿瘤的诊疗理念经历了从经验医学到循证医学的过渡,已步入“精准医学”的发展阶段。在精准医学中,精准诊断是指导临床决策、制定个体化诊治方案的重要依据,是实施精准治疗的必要前提。然而,由于恶性肿瘤具有时空异质性,给肿瘤精准诊断带来挑战,严重制约了肿瘤精准医疗效率的提升。分子影像能够实现肿瘤关键靶点的分子水平定性、定量检测,兼具解剖形态学和功能代谢检测的特点,能够更全面、直观地揭示肿瘤恶性生物学行为,从而为肿瘤精准诊断、指导肿瘤靶向及免疫治疗提供科学依据。借助多功能分子成像探针平台携载治疗药物或选择同时具有成像和治疗作用的放射性核素进行标记,分子影像又能同时实现肿瘤的精准治疗。因此,基于分子影像的精准医学可视化将在基础研究、转化医学以及健康医学领域发挥重要作用,尤其是随着分子影像技术的飞速发展,分子成像早已走出实验室,进入临床转化的关键阶段。其中,放射性核素分子成像凭借独特的优势走到了转化应用的技术前沿,为实现肿瘤精准诊疗带来新的机遇。本文将重点综述目前放射性核素分子影像在临床精准诊断中发挥的作用和价值,以期为致力于肿瘤研究的医务工作者和科研人员提供最新的技术讯息及研发思路。     

Noninvasive Determination of the IDH Status of Gliomas Using MRI and MRI-Based Radiomics: Impact on Diagnosis and Prognosis

Gliomas are the most common primary malignant brain tumors in adults. The fifth edition of the WHO Classification of Tumors of the Central Nervous System, published in 2021, provided molecular and practical approaches to CNS tumor taxonomy. Currently, molecular features are essential for differentiating the histological subtypes of gliomas, and recent studies have emphasized the importance of isocitrate dehydrogenase (IDH) mutations in stratifying biologically distinct subgroups of gliomas. IDH plays a significant role in gliomagenesis, and the association of IDH status with prognosis is very clear. Recently, there has been much progress in conventional MR imaging (cMRI), advanced MR imaging (aMRI), and radiomics, which are widely used in the study of gliomas. These advances have resulted in an improved correlation between MR signs and IDH mutation status, which will complement the prediction of the IDH phenotype. Although imaging cannot currently substitute for genetic tests, imaging findings have shown promising signs of diagnosing glioma subtypes and evaluating the efficacy and prognosis of individualized molecular targeted therapy. This review focuses on the correlation between MRI and MRI-based radiomics and IDH gene-phenotype prediction, discussing the value and application of these techniques in the diagnosis and evaluation of the prognosis of gliomas.     

Current perspectives in gliomas

The annual incidence of primary central nervous system tumors, including gliomas, is increasing, however, the prognosis of these tumors remains poor with a median survival of only 5 years. The imaging of tumors by computerised tomography, magnetic resonance imaging and newer methods such as positron emission tomography and proton magnetic resonance spectroscopy (¹H-MRS) is increasing our knowledge of tumor biology and extent of the disease. Advances within the field of neurosurgery have improved operative procedures reducing mortality and morbidity. Furthermore, radiotherapy planning, tumor targeting and repositioning for treatment have all improved initial tumor management The role of adjuvant chemotherapy remains controversial. Chemotherapy for advanced and recurrent disease has been extensively investigated, and although improvements in quality of life have been recorded, no prolongation of survival has been documented. With new discoveries and increasing knowledge of the physiology and molecular biology of these tumors the potential for targeting therapy at a genetic level is becoming increasingly promising. This review provides an overview of these current perspectives in glioma management.     

Prediction of proapoptotic anticancer therapeutic response in vivo based on cell death visualization and TRAIL death ligand-receptor interaction

Tumor growth is often associated with insufficient apoptosis. The Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) and its proapoptotic receptors death receptor 4 (DR4) and DR5 agonistic monoclonal antibodies are being developed as targeted therapeutics because they kill cancer cells while sparing normal cells. A challenge to targeted therapeutics is the selection of patients who are most likely to benefit from targeted drugs because of the heterogeneity of cancer. Molecular imaging may be useful in targeted drug development by assessing the target expression and drug-target interaction, and for predicting therapeutic response. We hypothesized that the cell surface expression level of DR4/5 may predict the proapoptotic targeted therapeutic response if the signaling pathway downstream is intact. The goal of this proof-of-concept study was to develop a molecular imaging strategy to predict proapoptotic anti-cancer therapy response at an early stage of treatment. TRAIL and the DR5 agonistic monoclonal antibody HGS-ETR2 (Lexatumumab, TRM-2) were labeled with a near-infrared dye and these were used to image the TRAIL receptors on cultured TRAIL sensitive and TRAIL resistant human tumor cells as well as tumor xenografts. Imaging of cells and tumor-bearing animals was conducted with near infrared fluorescence imagers and apoptosis in cells was assessed by western blots of PARP-cleavage and flow cytometry of sub-G1 content. Apoptosis in tumors was evaluated by imaging near-infrared dye-labeled Annexin V and tumor tissue activated caspase-3 staining. Both in vitro and in vivo studies showed that imaging of death inducing ligand-receptor interaction was consistent with the apoptosis readout. Thus TRAIL sensitive tumors that express TRAIL receptors underwent cell death following treatment whereas tumors lacking TRAIL receptor expression were shown to be TRAIL resistant. In vivo molecular imaging of TRAIL receptor expression correlated with response to TRAIL therapy and an apoptotic response in vivo.     

Inhibition of angiogenesis and invasion in malignant gliomas

Malignant gliomas confer a dismal prognosis. As the molecular events that underlie tumor angiogenesis are elucidated, angiogenesis inhibition is emerging as a promising therapy for recurrent and newly diagnosed tumors. Data from animal studies suggest that angiogenesis inhibition may promote an invasive phenotype in tumor cells. This may represent an important mechanism of resistance to antiangiogenic therapies. Recent studies have begun to clarify the mechanisms by which glioma cells detach from the tumor mass, remodel the extracellular matrix and infiltrate normal brain. An array of potential therapeutic targets exists. Combination therapy with antiangiogenic and novel anti-invasion agents is a promising approach that may produce a synergistic antitumor effect and a survival benefit for patients with these devastating tumors.     

Understanding the molecular pathogenesis and prognostics of bladder cancer: an overview

The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high-grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article outlines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.