In silico antiplasmodial effects of phytocompounds derived from Andrographis paniculata on validated drug targets of different stages of Plasmodium falciparum

Background:Andrographis paniculata has been widely reported as an herbal plant for malaria treatment.The increasing rate of resistance to recommended antimalarial drugs has justified the need for a continuous search for new and more potent drugs that target all stages of the Plasmodium falciparum life cycle from natural plant sources.This study aimed to determine the antiplasmodial effect of phytocompounds derived from A.paniculata on the stages of plasmodium falciparum.Methods:Phytocompounds from A.paniculata were identified by Gas Chromatography-Mass Spectrophotometry(GCMS)analysis.The phytocompounds were screened for their druggability using Lipinski’s rule of five and subjected to Absorption,Distribution,Metabolism,Excretion,Toxicity(ADMET)and druglikeness analysis.The phytocompounds were docked against some validated drug targets at different stages of Plasmodium falciparum(hepatic,asexual,sexual,and vector targets)using PyRx software to analyze the inhibitory potential and protein-ligand interaction.Thereafter,the stability and flexibility of the best complexes were assessed through molecular dynamics simulations at 50ns using WebGRO.Result:The 7a-Isopropenyl-4,5-dimethyloctahydroinden-4-yl exhibited a higher binding affinity and better stability throughout the simulation period with P.falciparum dihydrofolate reductase-thymidylate synthase and Plasmodium falciparum M1 alanyl aminopeptidase for asexual blood stage and gametocyte stage of Plasmodium falciparum,respectively than the existing drugs.Meanwhile,N-Ethyl-3-methoxy-4-methylphenethylamine was also found to have a higher binding affinity and more stability throughout the simulation period with P.falciparum purine nucleoside phosphorylase and Plasmodium falciparum gametocyte surface protein for Hepatic schizonts stage of Plasmodium falciparum and gametocyte transmission blocking stage,respectively,than the existing drugs.Conclusion:The 7a-Isopropenyl-4,5-dimethyloctahydroinden-4-yl and N-Ethyl-3-methoxy-4 methylphenethylamine from A.paniculata are predicted as an antimalarial drug candidate.Thus,it is recommended that in vitro and in vivo bioassays be conducted on these hit compounds to validate these predictions.

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous seizures.The pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy.Although current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting epileptogenesis.To this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets.Emphasizing early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden.In this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

Molecularly imprinted nanoparticles and their releasing properties, bio-distribution as drug carriers

Molecular imprinted nanoparticles(MINPs) can memorize the shape and functional group positions complementary to template, which account for the large drug loading capacity and slow drug release behavior as drug carriers. We synthesized MINPs via precipitation polymerization with vinblastine(VBL) as a model drug, and investigated the drug loading,releasing property in vitro and bio-distribution in vivo. The obtained MINPs, from 300 to 450 nm,had smooth surface and favorable dispersibility. The entrapment efficacy and drug loading capacity of VBL loaded MINPs(MINPs-VBL) were 83.25% and 8.72% respectively. In PBS(pH 7.4),MINPs-VBL showed sustained release behavior. The cumulative release percentage reached about 70% during 216 h and no burst release was observed. The releasing behavior of MINPsVBL in vitro conformed to the first-order kinetics model. MINPs-VBL and commercially available vinblastine sulfate injection(VBL injection) were injected via tail vein of SD rats respectively to investigate the bio-distribution. MINPs-VBL group showed higher concentration of VBL in tissues and serum than VBL injection group after 60 min, and the drug level in liver was the highest. MINPs-VBL exhibited liver targeting trend to some extent, which was based on the evaluation of drug targeting index(DTI) and drug selecting index(DSI).

Overview of Research and Development for Anticancer Drugs

Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.

Evaluation of Targeted Therapy for Locally Advanced or Metastatic Renal Cell Carcinoma in Tunisia

Introduction: Renal cell carcinoma (RCC) is known to be chemo resistant but with the introduction of targeted therapies;there has been a “revolution” in its treatment strategies. The only targeted therapy available in Tunisia for the treatment of metastatic and/or locally advanced RCC is sunitinib. Objective of the Study: To evaluate therapeutic results and tolerance of sunitinib in metastatic and/or locally advanced RCC. Subjects and Methods: This was a retrospective study covering a period of six years (from January 2008 to January 2014) conducted in 5 medical oncology departments in Tunisia. The population of the study consisted of 29 patients treated with sunitinib for metastatic and/or locally advanced RCC. Results: The mean age of patients was 51 years. Three patients had tumor recurrence and 26 patients had a metastatic RCC. The prognosis was good for 5 patients, intermediate for 19 patients and poor for 5 patients. The median duration of treatment was 5 months. Because of side effects, treatment was discontinued in 12.5% of cases and the dose was reduced in 10.3% of cases. Side effects consisted of asthenia (95.8%), stomatitis (70.8%), anemia (50%), hand-foot syndrome (55.8%) in addition to nausea and vomiting (54.2%). Objective response was observed in 37.5% of patients after 3 months of treatment and in 50% after 6 months. The median progression-free survival was 14 months (95% CI, 7.9 to 20.6). The median overall survival was 22 months (95% CI, 15.6 to 28.7). Conclusion: The prognosis of RCC in Tunisian patients has clearly improved with the introduction of sunitinib, but other therapies with a proven efficacy as a first and second line therapy should be considered.

Roles of lncRNAs in pancreatic ductal adenocarcinoma: Diagnosis,treatment, and the development of drug resistance

Background: Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs(lnc RNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. Data sources: We carried out a systematic review on lnc RNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lnc RNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in Pub Med with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lnc RNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. Results: Lnc RNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting mi RNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. Conclusions: The functional lnc RNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.

槐耳颗粒联合分子靶向药物治疗脾虚型原发性肝癌的临床疗效

目的 探讨槐耳颗粒联合分子靶向药物治疗脾虚型原发性肝癌(PHC)的临床疗效及对肝功能、免疫功能的影响。方法 回顾性分析2020年1月—2021年12月本院收治的PHC患者70例,按就诊先后顺序分为A组和B组各35例。两组患者均实施常规支持治疗。A组在常规治疗上使用分子靶向药物治疗,B组在A组的基础上联合槐耳颗粒治疗,两组患者皆进行4周的治疗。对两组治疗前后中医证候积分、生活质量、肝功能及免疫功能指标的变化实施观察,并评价两组临床疗效与安全性。结果 B组总有效率(97.14%)显著高于A组(80.00%)(P<0.05)。治疗前,两组中医症候积分比较,差异无统计学意义(P>0.05);两组中医症候积分在治疗后均降低,且B组积分低于A组(P<0.05);治疗前,两组患者的CD8^(+)、CD4^(+)和CD4^(+)/CD8^(+)比较,差异无统计学意义(P>0.05);治疗后,两组患者的CD8^(+)、CD4^(+)水平较治疗前显著降低;B组CD4^(+)/CD8^(+)水平较治疗前提高,A组CD4^(+)/CD8^(+)水平较治疗前降低,且B组的CD8^(+)水平低于A组,CD4^(+)与CD4^(+)/CD8^(+)水平高于A组(P<0.05)。治疗前,两组的AST、ALT和TBIL水平比较,差异无统计学意义(P>0.05);治疗后两组AST、ALT和TBIL水平显著减少(P<0.05),且B组明显低于A组(P<0.05)。B组不良反应发生率(11.42%)高于A组(8.57%),但两组高血压、手足综合征、皮疹、恶心呕吐及腹泻等不良反应比较,差异无统计学意义(P>0.05)。治疗后两组生活质量均上升,且B组生活质量优于A组(P<0.05)。结论 槐耳颗粒联合分子靶向药物治疗PHC患者疗效确切,可减轻患者临床症状,改善患者的肝功能以及免疫功能指标,安全性较高,可在临床推广。

关于北京医院老年类风湿关节炎生物分子靶向治疗的调查研究

目的:调查近3年就诊于北京医院的老年类风湿关节炎患者生物靶向制剂使用情况、使用及未使用生物靶向制剂治疗联用激素情况,疾病缓解程度、药物使用依从性,以及药物停用情况。方法:选取2019年6月至2022年6月就诊于北京医院的180例老年类风湿关节炎患者为研究对象,利用院内电子病历系统提取患者的就医信息,包括性别、年龄、病程、实验室检查、药物使用情况,及停药原因,采用SPSS 25.0软件进行统计分析。结果:①180例老年类风湿关节炎患者中,选择使用生物分子靶向治疗患者51例,药物选择按比例由高到低依次为:肿瘤坏死因子拮抗剂、Janus激酶抑制剂、白细胞介素-6受体拮抗剂。②追踪规律使用生物靶向制剂者25例,统计患者初诊、用药3个月、6个月肿胀及压痛关节数量、C反应蛋白检测结果等,依据SDAI评分计算公式对患者疾病活动程度进行判断,规律使用生物制剂治疗半年后均可达到疾病缓解。③追踪统计未遵医嘱规律进行药物治疗的26例患者停药原因,其中以感染、肿瘤较为多见。④180例患者中,规律生物分子靶向治疗患者中激素使用率较传统改善病情抗风湿药治疗患者明显减低。结论:目前就诊于北京医院的老年类风湿关节炎患者,生物制剂或分子靶向治疗的药物选择主要为肿瘤坏死因子受体拮抗剂;规律使用生物制剂或分子靶向药物可以有效控制疾病,减轻关节肿痛症状,降低疾病活动度;老年类风湿关节炎治疗过程中应注意监测感染及肿瘤风险,并做好患者随访,与患者家属合作积极促进患者规律用药,减少因依从性差所致停药情况。

滋燥养荣方治疗抗肿瘤靶向药所致大鼠皮肤干燥的分子机制

目的 基于网络药理学分析和动物实验探讨中药滋燥养荣方治疗抗肿瘤靶向药所致皮肤干燥的分子机制。方法采用在线数据库筛选滋燥养荣方各单味药成分的靶点和皮肤干燥及瘙痒的靶点,对共同靶点进行分析,通过通路富集预测中药可能的效应途径。应用靶向药吉非替尼建立与患者皮肤干燥皮损表现一致的大鼠模型,分为模型组、阳性对照组和中药组,分别予生理盐水、维生素E乳、中药进行干预,以正常大鼠作为正常对照组,观察各组皮肤表型、组织病理学变化、信号通路相关蛋白和炎症因子表达。结果 滋燥养荣方各单味药筛选出预测靶点共3 125个,靶向药所致皮肤干燥及伴有瘙痒的对应靶点共660个。对173个共同靶点进行分析,通路富集预测结果显示表皮角质细胞内磷脂酰肌醇-3-激酶(PI3K)-丝苏氨酸蛋白激酶B (Akt)通路可能是中药起效的信号途径。动物实验表明,与正常对照组比较,其余各组均出现靶向药相关的皮损、结痂、脱屑等皮肤干燥表现;与模型组比较,阳性对照组和中药组小鼠的皮肤干燥均改善,中药组小鼠皮损愈合、毛发生长情况优于阳性对照组。与正常对照组比较,模型组表皮增厚(P<0.05);与模型组比较,阳性对照组、中药组表皮厚度变薄(P<0.05)。与正常对照组比较,模型组Akt蛋白和p-Akt 308蛋白染色呈棕黄色,强度较弱;与模型组比较,中药组Akt蛋白和p-Akt 308蛋白染色呈棕黄色,强度较强,且强于阳性对照组,与正常对照组相近。各组p-Akt 473蛋白染色强度差异不明显。Western blotting检测结果:与正常对照组比较,中药组皮肤组织中p-Akt 308蛋白相对表达量低(P<0.05);与模型组比较,中药组皮肤组织中p-Akt 308蛋白相对表达量高(P<0.05)。各组皮肤组织及血清炎症因子水平比较差异无统计学意义(P>0.05)。结论 中药滋燥养荣方能缓解抗肿瘤靶向药所致大鼠局部皮肤炎症、促进皮肤修复,其分子机制可能与Akt相关信号通路有关。

奥希替尼在老年非小细胞肺癌患者靶向治疗中的应用效果及对T细胞水平的影响

目的 探讨奥西替尼在老年非小细胞肺癌患者靶向治疗中的效果及对免疫水平的影响。方法 回顾性选择2018年1月至2020年12月老年非小细胞肺癌患者116例研究,根据治疗方法不同分为2组,各58例。对照组采用常规放化疗治疗,观察组在对照组基础上联合奥西替尼治疗,3个月治疗后评估患者效果,比较2组总有效率、T细胞水平(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、肿瘤标志物水平、不良反应发生率。结果 观察组治疗3个月总有效率为44.8%高于对照组25.9%(P<0.05);2组治疗后3个月CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均低于治疗前(P<0.05);CD8^(+)水平高于治疗前(P<0.05);观察组治疗后3个月CD3^(+)(58.95±4.21)%、CD4^(+)(32.59±3.11)%、CD4^(+)/CD8^(+)(1.21±0.22)高于对照组(P<0.05);CD8^(+)(26.81±3.32)%低于对照组(P<0.05);观察组干预3个月后CA125(91±8)U/ml、CYFRA21-1(1.26±0.24)μg/L及癌胚抗原(CEA)水平(34±5)μg/L均低于对照组(P<0.05);2组不良反应发生率差异无统计学意义(P>0.05)。结论 奥西替尼用于老年非小细胞肺癌患者靶向治疗中,能获得较好的总有效率,对患者T细胞水平影响较小,可降低肿瘤标志物水平,未增加不良反应发生率,值得临床推广应用。

微波消融联合TKI分子靶向治疗非小细胞肺癌的研究现状

肺癌作为高发且致死率极高的恶性肿瘤,尽管通过手术、化放疗、免疫治疗、分子靶向等在临床上取得显著的疗效,但患者的5年生存率仍然不尽人意,微波消融作为一种较新的局部治疗方法,以其微创、副作用小、能够延长生存期并保留器官完整性的优势,正逐渐成为肺癌治疗领域的焦点。该文旨在总结微波消融联合奥希替尼的协同治疗效果,分析其临床效益,并对微波消融与分子靶向药物联合治疗前景进行展望。

基于妇科肿瘤耐药治疗中工程化外泌体的应用研究进展

妇科恶性肿瘤严重威胁着女性健康,在女性各类疾病中其发病率和死亡率均位居前列,关键原因在于传统化疗对复发、耐药患者的疗效欠佳。近年来,探讨肿瘤细胞化疗的耐药机制,开发新型药物逆转耐药已成为妇科肿瘤研究者关注的热点。外泌体(exosome)是一种来源于细胞内溶酶体微粒内陷的多囊泡体,具有低免疫原性、先天靶向性及获得靶向性和高传递效率等生物学特性。因此,外泌体可作为一种理想的、天然的纳米递送药物载体,不仅可以降低肿瘤细胞对化疗药物的耐药性,提高药物治疗效果,还可以减少化疗药物对全身的毒副反应。本文就外泌体作为妇科肿瘤耐药治疗中药物载体的研究进展进行综述,以期对妇科肿瘤的临床治疗提供帮助。

靶向异常通路的动脉性肺动脉高压新型药物研发

动脉性肺动脉高压(pulmonary arterial hypertension,PAH)是以肺血管阻力和肺动脉压力升高为主要表现的肺血管疾病,肺小血管重塑是其重要病理改变,如不及时治疗可导致右心室衰竭,威胁生命。目前针对PAH的治疗选择有限,已上市药物的主要作用是扩张肺血管,虽能缓解症状,但对预后的改善效果不佳。近年来,对PAH发病机制的研究取得了多项突破,多种信号通路的异常对PAH的作用已被逐渐阐明,以这些通路中的关键成员为靶点,已有多种新型药物正在研发和开展临床试验。本综述将这些疾病相关的信号通路归纳为5类,讨论针对这些异常通路的药物研发最新进展,重点关注已进入Ⅱ期临床试验阶段的新药物,探讨其作用机制及疗效,以期为今后PAH的新药研发提供参考。

分子靶向药物联合CAR-T细胞疗法在淋巴瘤治疗中的应用进展

嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞疗法在淋巴瘤中的疗效得到了肯定,但部分患者存在耐药,安全性等方面问题也影响其预后。分子靶向药物可以调节肿瘤微环境、增强肿瘤特异性抗原表达能力,有助于减少抗原逃逸的发生。部分小分子靶向药物可以通过调节抗凋亡和促凋亡信号传导之间的平衡,诱导肿瘤细胞死亡;还可以调节免疫抑制和免疫激活信号通路提高CAR-T细胞疗法的抗肿瘤功效,逆转CAR-T细胞的耗竭表型,增强其抗肿瘤效果。分子靶向药物与CAR-T细胞在淋巴瘤中联合使用的疗效、安全性及发挥作用的机制也越来越受关注。本文就CAR-T细胞疗法联合常用分子靶向药物在淋巴瘤治疗中的研究进展进行综述。

多发性骨髓瘤耐药机制和分子靶向治疗新进展——第20届国际骨髓瘤学会年会研究热点报道

多发性骨髓瘤(MM)是一种血液恶性肿瘤,其特征为恶性浆细胞的克隆性增殖。蛋白酶体抑制剂、免疫调节药物以及自体造血干细胞移植治疗明显改善了MM患者的生活质量和生存状况,然而几乎所有患者都将产生耐药导致疾病复发难治,预后较差。因此,探究MM患者耐药性产生的分子机制,寻找新的治疗靶点并开发新的靶向治疗策略尤为重要。现对MM耐药机制和分子靶向治疗研究的最新进展进行综述。

基于网络药理学和分子对接技术探讨柴胡疏肝散改善肠黏膜损伤的作用机制

目的利用网络药理学探讨柴胡疏肝散改善肠黏膜损伤的作用机制,并通过分子对接技术加以验证。方法利用TCMSP数据库筛选出柴胡疏肝散各中药的活性成分及作用靶点信息,利用GeneCards和OMIM等数据库收集肠黏膜损伤疾病的靶点;将柴胡疏肝散的活性成分靶点与肠黏膜损伤疾病靶点的交集作为关键靶点;利用STRING数据库构建蛋白互作网络(PPI);用Cytoscape 3.9.1软件构建柴胡疏肝散-活性成分-潜在靶点网络;运用David网站进行GO分析和KEGG富集分析。应用Pymol、AutoDock Tools等软件对核心成分与关键靶点进行分子对接的验证,并利用Pymol进行可视化分析。结果获得柴胡疏肝散的活性成分靶点432个,肠黏膜损伤疾病靶点1307个,取交集得到柴胡疏肝散与肠黏膜损伤的关键靶点142个;用PPI网络对关键靶点进行分析,得到核心靶点蛋白激酶B(Akt1)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF)、IL-1β;富集分析结果显示,柴胡疏肝散可能通过调节高级糖基化终末产物-受体(AGE-RAGE)、IL-17和TNF等信号通路来改善肠黏膜损伤。分子对接结果显示,核心化合物β-谷甾醇与Akt1、IL-6、TNF等有良好的结合活性。结论柴胡疏肝散可通过多靶点、多通路发挥改善肠黏膜损伤的作用,为治疗肠黏膜损伤的新药研究提供了新的思路。

抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展

胃癌(GC)是极具异质性和侵袭性的消化系统恶性肿瘤之一,传统化疗药物及曲妥珠单抗等人表皮生长因子受体2(HER2)靶向药物在GC的治疗过程中仍然存在耐药性发生率高、毒副作用大、患者耐受差等缺点。因此,研发更为有效的抗GC药物势在必行。目前针对HER2的新型靶向药层出不穷,但在某些情况下无效或产生耐药,这与HER2在某些GC细胞中低表达有关,HER2低表达(HER2 IHC1+或IHC2+/ISH-)约占全部类型的40%~60%,但在临床实践中,这类患者仍被报告为HER2阴性GC。因此准确检测HER2表达状态对于确定可能受益于曲妥珠单抗治疗的患者至关重要。抗体药物偶联物(ADC)的出现为HER2阳性GC提供了新的治疗选择,凭借其精准高效的抗肿瘤作用,有望在未来替代传统GC化学疗法。近期有研究发现ADC可能在HER2低表达GC中具有潜在抗肿瘤活性,相关临床研究正在评估其在HER2低表达GC治疗中的有效性和安全性。本文就靶向治疗时代ADC在HER2低表达GC患者中的应用和最新研究进展作一综述,并讨论HER2靶向ADC在应用和研发过程中面临的挑战。

从温病学理论探讨论治肿瘤分子靶向药物相关皮肤毒性

分子靶向药物已成为许多肿瘤治疗的重要药物,然而皮肤毒性是运用靶向药物发挥抗肿瘤疗效时出现的主要不良反应,严重影响肿瘤患者治疗期间的生活质量,因此,缓解其不良反应对于提高患者的治疗依从性、生活质量甚为重要。从皮肤毒性临床表现及发生演变规律看,均符合温热病演变规律。采用温病学卫气营血辨证论治体系进行综合诊治,把“透法”思维贯穿在诊治全过程,取得较好的临床疗效,为靶向药物皮肤毒性的治疗提供全程中医药干预治疗思路并提高肿瘤患者生活质量。

Anti-tumor targeted drug delivery systems mediated by aminopeptidase N/CD13

Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing the Asn-Gly-Arg(NGR)motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells.This article reviews the literature and recent developments related to APN/CD13,its role in tumor growth and some antitumor drug delivery systems containing NGR peptides designed to target APN/CD13.

Novel therapeutic approaches targeting L-type amino acid transporters for cancer treatment

L-type amino acid transporters(LATs) mainly assist the uptake of neutral amino acids into cells. Four LATs(LAT1, LAT2, LAT3 and LAT4) have so far been identified. LAT1(SLC7A5) has been attracting much attention in the field of cancer research since it is commonly up-regulated in various cancers. Basic research has made it increasingly clear that LAT1 plays a predominant role in malignancy. The functional significance of LAT1 in cancer and the potential therapeutic application of the features of LAT1 to cancer management are described in this review.