微小RNA-551a参与晚期肝细胞癌患者索拉非尼应答机制研究

目的：索拉非尼是晚期肝细胞癌（hepatocellular carcinoma,HCC）患者化学药物治疗的标准一线用药之一。本研究旨在探索微小RNA(microRNA,miRNA)-551a在索拉非尼应答中的作用。方法：通过综合生物信息学方法分析HCC相关miRNAs表达谱特征,并鉴定索拉非尼应答miRNAs及其相关分子机制。选取2021年2月至2022年2月皖西卫生职业学院附属医院收治的24例晚期HCC患者。选择同期收治的18例肝硬化患者作为对照组。验证索拉非尼应答miRNAs的表达特征及预测HCC预后的价值。结果：高表达miRNA-551a的晚期HCC患者预后较差,其表达被索拉非尼抑制。miRNA-551a通过多种促癌通路和自噬途径参与HCC进展及索拉非尼应答机制。临床验证队列中,索拉非尼治疗前晚期HCC患者血清mi RNA-551a表达水平高于对照组（P<0.05）,治疗后其miRNA-551a表达水平降低（P<0.05）。治疗前血清高表达miRNA-551a的晚期HCC患者受益于索拉非尼治疗（P<0.05）。单因素及多因素Cox比例回归模型也证实,治疗前血清m...     

含奥沙利铂化疗方案治疗晚期原发性肝细胞癌的研究进展

索拉非尼是目前唯一被多国批准的治疗晚期原发性肝细胞癌（HCC）的分子靶向药物,但其对生存期改善有限,最终出现病情进展。近几年,含奥沙利铂的化疗方案显示出良好的临床疗效,且患者耐受性可,为晚期 HCC 患者提供了新的治疗选择。     

肝细胞癌免疫治疗的临床研究进展

早期肝细胞癌（hepatocellular carcinoma,HCC）手术切除、消融等局部治疗效果较好,但多数患者就诊时已属晚期,局部治疗效果有限,系统性治疗如索拉非尼（Sorafenib）等成为主要的治疗选择,但效果并不理想。免疫治疗近年获得了突破性进展,其疗效和安全性已在多种恶性肿瘤的临床实践中得到证实,有望改变现有的HCC治疗模式。本文就HCC免疫治疗的临床研究进展作一综述。     

索拉非尼治疗肝细胞癌进展后的二线治疗

原发性肝癌是临床最常见的恶性肿瘤之一,其病理分型绝大多数属于肝细胞癌（HCC）。索拉非尼是第一个亦是目前唯一一个被多个国家批准用于治疗HCC的分子靶向药物,但其疗效有限,多数患者口服一段时间后会出现耐药而病情进展,对于这些患者目前尚缺乏标准的二线治疗方案,本文就索拉非尼治疗HCC耐药后的最新二线治疗研究进展作一综述。     

PI3K/AKT/mTOR信号通路介导索拉非尼治疗原发性肝癌耐药机制的研究进展

索拉非尼（sorafenib）作为原发性肝癌（hepatocellular carcinoma,HCC）靶向治疗的一线药物已广泛应用于临床,然而部分HCC患者对索拉非尼治疗耐药导致临床疗效欠佳,联合其他靶向药物的临床实验仍未取得突破,故深入研究索拉非尼耐药机制,逆转索拉非尼耐药对于改善肝癌治疗的预后具有重要意义。最新研究发现,PI3K/AKT/mTOR信号通路在索拉非尼耐药机制中起重要作用,本文将从PI3K/AKT/mTOR信号通路促进肿瘤血管生成、参与细胞自噬、抑制肿瘤细胞凋亡并促进其增殖、与RAS/RAF/ERK/MEK信号通路交联及其促进上皮-间质转化等几个方面,概述其在索拉非尼治疗原发性肝癌时产生耐药的机制,为进一步开发治疗原发性肝癌的新型药物提供研究方向。     

2014年ASCO消化道肿瘤研讨会对晚期原发性肝癌研究进展的讨论

原发性肝癌是临床常见的消化系统恶性肿瘤之一,索拉非尼开启了肝癌分子靶向药物治疗的新时代,但其临床疗效仍然有限。2014年ASCO消化道肿瘤研讨会（GI）报道了靶向药物roTOR抑制剂依维莫司在晚期肝细胞癌中的Ⅲ期临床研究和抗ANG类抗肿瘤血管生成药物Trebananib在晚期肝细胞癌中的Ⅱ期临床研究结果,但结果均不尽如人意。索拉非尼仍然是晚期肝细胞癌重要的靶向治疗药物,研究者对如何发挥其在肝癌患者中的最大疗效进行了进一步的探索。相信随着肿瘤分子生物学研究的不断深入,肝癌发生发展机制的逐步阐明,一些驱动基因的发现以及针对这些驱动基因的药物研发,肝癌的疗效终会出现一个跨越式的提高,给患者带来希望。     

舒尼替尼治疗肝癌引起病灶大面积坏死1例

肝细胞癌（hepatocellular carcinoma,HCC）是我国最常见的恶性肿瘤之一,目前手术切除仍是获得长期生存最重要的手段,但由于其起病隐匿,发展迅速,60％的患者确诊时已处于晚期,失去手术机会;即使能够手术切除,其复发率仍较高,因此药物治疗占有重要的地位。索拉非尼是唯一被多个国家批准用于治疗晚期不能手术HCC的分子靶向药物。     

分子靶向药物在肝细胞癌治疗中的临床研究进展

肝癌是全球第六大常见的恶性肿瘤,也是第四大肿瘤相关死亡原因,其中肝细胞癌（hepatocellular carcinoma,HCC）占90%,且80%以上的HCC发生在肝炎和肝硬化等患者中。对于HCC的治疗方面,仅20%的HCC患者可进行手术切除、肝脏移植或射频消融治疗,而晚期HCC患者无法进行根治性治疗,其生存率也逐渐下降。近年来,分子靶向药物治疗已成为研究热点,该类药物可通过特异性的与致癌位点靶向结合而发挥抗癌作用。目前,抗HCC的靶向药物主要分为一线药物与二线药物,其中一线药物主要包括索拉非尼、仑伐替尼,二线药物主要包括瑞戈非尼、卡博替尼及雷莫芦单抗等。本文对此类分子靶向药物在HCC治疗中的临床研究进展进行综述。      

长链非编码RNA与肝细胞癌索拉非尼耐药：分子机制与治疗靶点新进展

肝细胞癌(HCC)是一种发病率及死亡率较高的恶性肿瘤,以索拉非尼为代表的全身性药物治疗效果并不理想,索拉非尼耐药严重阻碍其临床应用。近年来不断有报道指出长链非编码RNA(lncRNA)参与调控HCC细胞增殖、凋亡、自噬、转移等生物学过程,诱导索拉非尼耐药。笔者以索拉非尼耐药机制为基点,综述多种与HCC索拉非尼耐药有关的lncRNA,揭示lncRNA通过调控癌细胞增殖与死亡、增强癌细胞恶性特征、促进药物外排的方式诱导HCC索拉非尼耐药,旨在为逆转索拉非尼耐药提供新的治疗思路和潜在靶点,增强HCC患者治疗有效性。     

节律性化疗在晚期肝细胞肝癌中的应用进展

原发性肝癌是我国常见的消化系统恶性肿瘤,其中以肝细胞肝癌（hepatocellular carcinoma,HCC）为最多见。多数HCC患者确诊时已为晚期,丧失了手术和局部治疗的机会,系统治疗被认为是晚期HCC的主要治疗方式。传统细胞毒类药物化疗对晚期HCC效果不明显,分子靶向药物索拉非尼虽有生存获益,但客观有效率仅为2%~3%,且价格昂贵。节律性化疗由于靶向肿瘤新生血管,在晚期转移性癌症中的治疗作用越来越受到关注。本文拟对节律性化疗在晚期HCC中的治疗进展做一简要综述。      

索拉非尼治疗肝细胞癌的现状

在我国肝细胞癌有较高的发病率、术后复发率和病死率。肝细胞癌对放化疗不敏感,尤其是进展期肝细胞癌尚缺乏有效的治疗手段。索拉非尼是第一个用于肝细胞癌临床治疗的分子靶向药物,是肝细胞癌药物治疗的里程碑。然而,在临床应用中存在耐药现象。因此,探究索拉非尼的耐药机制、寻找耐药的分子标记物有重要意义。本文对索拉非尼治疗肝细胞癌的现状进行综述。     

仑伐替尼治疗肝细胞癌的研究进展

肝细胞癌（hepatocellular carcinoma,HCC）是严重威胁人类生命健康的疾病之一,其发病率和死亡率逐年上升,具有发展迅速、高侵袭性和高复发性等特点。大多数患者确诊时已是进展期,而靶向治疗作为进展期肝癌的主要治疗策略,已广泛应用于临床。以往该类患者的一线治疗药物仅有索拉菲尼,但其不良反应大,肿瘤应答率低,对乙型肝炎病毒（hepatitis B virus,HBV）阳性患者的总生存率并无明显改善。近年来,新的靶向治疗药物仑伐替尼在肝癌的治疗研究中取得了良好的疗效,成为继索拉菲尼后治疗进展期肝癌的第2个一线药物。本文就仑伐替尼在治疗HCC中的研究进展进行综述。      

Long-term survival of patients with hepatocellular carcinoma with inferior vena cava tumor thrombus treated with sorafenib combined with transarterial chemoembolization:report of two cases and literature review

The prognosis of hepatocellular carcinoma （HCC） with tumor thrombus formation in the main vasculature is extremely poor. Sorafenib combined with transarterial chemoembolization is a novel treatment approach for advanced HCC. In this study, we report two HCC patients with inferior vena cava tumor thrombus who underwent the combination treatment. The overall survival times for these two patients were 44 months and 35 months, respectively. Our report suggests that sorafenib combined with transarterial chemoembolization may be a viable choice for patients with advanced HCC even with inferior vena cava tumor thrombus. Further studies are required to verify the efficacy and safety of this combination therapy for patients with advanced HCC with inferior vena cava tumor thrombus.     

Hepatic arterial infusion of chemotherapy for advanced hepatocellular carcinoma

Treatment of advanced hepatocellular carcinoma (HCC) remains a significant problem for clinicians. Sorafenib, the only approved agent, improves survival rate, but is associated with a low tumor response rate. Alternative approaches for the treatment of advanced HCC are urgently needed. Hepatic arterial infusion of chemotherapy (HAIC) is a promising modality for the treatment of advanced HCC. Since its introduction, there have been improvements in implantable pumps, in catheter implantation and in the convenience and safety of HAIC in general. Numerous clinical studies have shown that HAIC provides moderate therapeutic efficacy with substantially favorable toxicity profiles in selected patient groups with advanced HCC. However, the lack of large randomized studies means that HAIC is not yet a well‐established treatment for advanced HCC. We believe there is an urgent need for the further investigation of HAIC for the treatment of advanced HCC.     

Targeted therapy for hepatocellular carcinoma: novel agents on the horizon

Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for 90% of primary liver cancers. In the last decade it has become one of the most frequently occurring tumors worldwide and is also considered to be the most lethal of the cancer systems, accounting for approximately one third of all malignancies. Although the clinical diagnosis and management of early-stage HCC has improved significantly, HCC prognosis is still extremely poor. Furthermore, advanced HCC is a highly aggressive tumor with a poor or no response to common therapies. Therefore, new effective and well-tolerated therapy strategies are urgently needed. Targeted therapies have entered the field of anti-neoplastic treatment and are being used on their own or in combination with conventional chemotherapy drugs. Molecular-targeted therapy holds great promise in the treatment of HCC. A new therapeutic opportunity for advanced HCC is the use of sorafenib (Nexavar). On the basis of the recent large randomized phase III study, the Sorafenib HCC Assessment Randomized Protocol (SHARP), sorafenib has been approved by the FDA for the treatment of advanced HCC. Sorafenib showed to be able to significantly increase survival in patients with advanced HCC, establishing a new standard of care. Despite this promising breakthrough, patients with HCC still have a dismal prognosis, as it is currently the major cause of death in cirrhotic patients. Nevertheless, the successful results of the SHARP trial underscore the need for a comprehensive understanding of the molecular pathogenesis of this devastating disease. In this review we summarize the most important studies on the signaling pathways implicated in the pathogenesis of HCC, as well as the newest emerging drugs and their potential use in HCC management.     

lncRNA在肝细胞癌索拉非尼耐药中的最新研究进展

肝细胞癌(Hepatocellular carcinoma,HCC)是全球最常见和最致命的癌症之一。大多数中晚期患者接受药物为主的治疗,索拉非尼(Sorafenib)作为晚期肝细胞癌的独特靶向药物,在临床上得到了广泛应用。然而,索拉非尼靶向治疗不仅单药有效率低,且耐药性也是亟待解决的大问题。最近研究显示长链非编码RNA(Long non-coding RNA,lncRNA)与肝细胞癌的发生发展、侵袭转移、预后及耐药有着密不可分的联系,并且在耐药研究方面成为新兴热点。本文就lncRNA在肝细胞癌索拉菲尼耐药中的最新发现及调控耐药性的具体机制展开综述。     

Enhancing the efficacy of photodynamic therapy by a chinese herbal medicine for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) ranks the sixth among the most common malignancies, with chronic HBV infection being the most common cause. HCC is more common in Africa, China and south-east Asia, but its incidence in the USA, Canada and Australia is rising. Current treatment modalities for HCC are not effective, and only a small percentage of patients are suitable for surgical resection and liver transplantation. Thus other treatment options and improvement of available modalities are badly in need. Photodynamic therapy (PDT) may have some therapeutic benefit for patients with HCC. The study by Tang et al. has implicated that coupled with Pheophorbide a (Pa), PDT may offer therapeutic benefit for patients with HCC. Inhibition of cell proliferation and induction of apoptosis by Pa may be mechanistically responsible for Pa-PDT. As Pa is an extract from a Chinese herbal medicine Scutellaria Barbata, which is widely available, less toxic and less expensive, such a combination may find a better clinical usage in the treatment of HCC patients. More studies are mandatory to fully elucidate the efficacy and mechanisms of Pa-mediated PDT.     

Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5–30%. In China, HCC seriously threatens the nation''s health; the incidence of HCC ranks fourth among all theriomas, and the mortality rate is the third highest worldwide. The main therapies for HCC are surgical treatment or liver transplantation; however, most patients with HCC will experience postoperative recurrence or metastasis, eventually resulting in mortality. As for advanced or unresectable HCC, the current appropriate treatment strategy is transarterial chemoembolization; however, limited therapeutic effect and natural or acquired drug resistance affect the efficacy of this approach. Previous studies have demonstrated that PD-L1 expression on host cells and myeloid cells plays an important role in PD-L1 blocked-mediated tumor regression. Thus, further research on programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is required. Countries including the United States, France, Britain and China have developed PD-1/PD-L1 blockers, including nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, toripalimab, sintilimab and camrelizumab. Notably, all of these blockers have therapeutic effect and influencing factors in HCC. Factors that influence the clinical outcome of PD-1 have also been discovered, such as inflammatory genes, specific receptors and signaling pathways. The discovery of these factors will help to identify novel methods, such as combination treatment, to decrease the influence of other factors on the efficacy of PD-1/PD-L1. Sorafenib and lenvatinib have been approved for first-line treatment for patients with advanced HCC. When first-line treatment frequently fails, pembrolizumab and ipilimumab plus nivolumab are used following sorafenib (but not lenvatinib) treatment in advanced HCC. Thus, tumor immunotherapy using PD-1/PD-L1 blockers exhibits promising outcomes for the treatment of HCC, and more novel PD-1/PD-L1 inhibitors are being developed to fight against this disease. The present review discusses the clinical results and influencing factors of PD-1/PD-L1 inhibitors in HCC to provide insight into the development and optimization of PD-1/PD-L1 inhibitors in the treatment of HCC.