Tasadenoturev

The dynamics of the glioma market are anticipated to change in the coming years owing to the positive outcomes of the emerging pipeline candidates during the developmental stage by key players, such as Bayer, VBL Therapeutics, Candel Therapeutics, AstraZeneca, DNAtrix, DelMar Pharmaceuticals, Chimerix, KaryoPharma, VBI Vaccines, Kazia Therapeutics, and others LAS VEGAS, May 1, 2023 /PRNewswire/ -- DelveInsight's Glioma Market Insights report includes a comprehensive understanding of current treatment practices, glioma emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan]. Key Takeaways from the Glioma Market Report As per DelveInsight analysis, the glioma market size in the 7MM was approximately USD 1 billion in 2022. According to the assessment done by DelveInsight, the estimated total incident glioma cases in the 7MM were approximately 47K in 2022. Leading glioma companies such as Bayer, Chimerix, Aivita Biomedical, Denovo Biopharma, Northwest Therapeutics, VBL Therapeutics, Laminar Pharmaceuticals, MedImmune, DNAtrix, Immunomic Therapeutics, Imvax, MimiVax, CNS Pharmaceuticals, Epitopoietic Research Corporation (ERC), Istari Oncology, SonALAsense, Kintara Therapeutics, Bristol Myers Squibb, Medicenna Therapeutics, BioMimetix, Eisai and Merck Sharp & Dohme, Kazia Therapeutics, Oblato, Genenta Science, Enterome, Inovio Pharmaceuticals, Karyopharm Therapeutics, VBI Vaccines, TME Pharma, Day One Biopharmaceuticals, Servier, Orbus Therapeutics, TVAX Biomedical, AnHeart Therapeutics, Beigene, SpringWorks Therapeutics, Forma Therapeutics, Hoffmann-La Roche, Incyte Corporation, Eli Lilly, and others are developing novel glioma drugs that can be available in the glioma market in the coming years. The promising glioma therapies in the pipeline include Regorafenib, ONC201, AV-GBM-1, Enzastaurin (DB-102), DCVax-L, Ofranergene Obadenovec (VB-111), LAM561 (2-OHOA), MEDI4736 (durvalumab), Tasadenoturev (DNX-2401), ITI-1000 (pp65 DC Vaccine), IGV-001, SurVaxM, Berubicin, GLIOVAC (Sitoiganap), Lerapolturev + Pembrolizumab, SONALA-001 + Exablate 2.0 Device, VAL-083 (dianhydrogalactitol), Pomalidomide, MDNA55, BMX-001, Lenvatinib ± Pembrolizumab, Paxalisib (GDC-0084), OKN-007, Temferon, EO2401, INO-5401+ INO-9012+ LIBTAYO (cemiplimab), Selinexor (KPT-330), Olutasidenib (FT-2102), VBI-1901, NOX-A12 (Olaptesed Pegol), Tovorafenib (DAY101), Vorasidenib (AG-881), Eflornithine, TVI-Brain-1, AB-218, BGB-290, Mirdametinib, FT-2102 (Olutasidenib), Vinblastine + Bevacizumab, Cobimetinib, PEMAZYRE (Pemigatinib), VERZENIO (abemaciclib) , and others. In December 2022, Chimerix announced the successful launch of the ONC201 Phase III ACTION study in patients with H3 K27M-mutant glioma. In June 2022, Day One Biopharmaceuticals announced positive initial data from its pivotal Phase II (FIREFLY-1) study with tovorafenib (DAY101) in relapsed pediatric low-grade glioma (pLGG). Discover which therapies are expected to grab the major glioma market share @ Glioma Market Report Glioma Overview Glioma is the most common kind of glial cell tumor in the central nervous system (CNS). Gliomas are infiltrative tumors that affect the brain tissue surrounding them. Glioblastoma is the most hazardous type of brain tumor, whereas pilocytic astrocytomas are the least dangerous. Previously, diffuse gliomas were classified into subgroups and grades depending on histopathologies, such as diffuse astrocytomas, oligodendrogliomas, or mixed gliomas/oligoastrocytomas. The specific etiology of glioma, like other primary brain tumors, remains unknown. However, certain variables may increase the risk of getting a brain tumor. Glioma symptoms vary depending on tumor type, size, location, and growth rate. Some common glioma symptoms include headache, nausea or vomiting, memory loss, urine incontinence, speech problems, and others. A medical history and a physical examination are used for glioma diagnosis. Glioma Epidemiology Segmentation DelveInsight estimates that there were approximately 47K incident cases of glioma in the 7MM in 2022. As per our analysis, the United States contributed to the largest incident population of glioma, acquiring ~40% of the 7MM in 2022. The glioma market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Total glioma incident cases Glioma grade-specific cases Glioma age-specific cases Glioma type-specific cases Download the report to understand which factors are driving glioma epidemiology trends @ Glioma Epidemiological Insights Glioma Treatment Market Glioma treatment is based on the type of glioma, its size and location, and the patient's unique characteristics. Chemotherapy and radiation therapy will be administered after surgery, particularly in individuals when the tumor cannot be removed entirely because it has invaded critical parts of the brain or is inaccessible. The typical glioma treatment protocol comprises surgery, chemotherapy, and radiation. Chemotherapy may include carmustine (BCNU), lomustine (CCNU), or gleostine (generic), cisplatin, carboplatin, etoposide, and irinotecan in case of low-grade glioma whereas temozolomide (TEMODAR) is the standard chemotherapy used in case of high-grade glioma majorly, Gliadel wafer implants (biodegradable discs injected with BCNU) are usually given as adjunctive treatment after surgery, although usage of Gliadel wafers remains a point of controversy due to its questionable survival benefits. Avastin (Genentech) and Temodar/Temodal (Merck), among others, are approved medications for HGG. However, due to patent expiration, the generic version of Temodar and biosimilars of Avastin are available on the glioma market. As generics and biosimilars are more cost-effective for patients than new medicines, intense competition exists among them. Furthermore, due to a lack of knowledge concerning bevacizumab's overall survival benefit, it is not recommended in unselected patients with newly diagnosed GBM. Currently, only one medication for LGG is approved, Tafinlar (dabrafenib) plus Mekinist (trametinib). Moreover, the current therapeutic market lacks a viable method for curing glioblastoma; therefore, the survival rate of people diagnosed with glioma remains poor. Glioma is incurable, and treatment choices are limited. Furthermore, the tumor has a high recurrence rate and a poor patient prognosis. In addition, there is currently no approved therapy for the unmethylated MGMT patient pool. To know more about glioma treatment guidelines, visit @ Glioma Management Glioma Therapies and Key Companies Regorafenib: Bayer ONC201: Chimerix AV-GBM-1: Aivita Biomedical Enzastaurin (DB-102): Denovo Biopharma DCVax-L: Northwest Therapeutics Ofranergene Obadenovec (VB-111): VBL Therapeutics LAM561 (2-OHOA): Laminar Pharmaceuticals MEDI4736 (durvalumab): MedImmune Tasadenoturev (DNX-2401): DNAtrix ITI-1000 (pp65 DC Vaccine): Immunomic Therapeutics IGV-001: Imvax SurVaxM: MimiVax Berubicin: CNS Pharmaceuticals GLIOVAC (Sitoiganap): Epitopoietic Research Corporation (ERC) Lerapolturev + Pembrolizumab: Istari Oncology SONALA-001 + Exablate 2.0 Device: SonALAsense VAL-083 (dianhydrogalactitol): Kintara Therapeutics Pomalidomide: Bristol Myers Squibb MDNA55: Medicenna Therapeutics BMX-001: BioMimetix Lenvatinib ± Pembrolizumab: Eisai and Merck Sharp & Dohme Paxalisib (GDC-0084): Kazia Therapeutics OKN-007: Oblato Temferon: Genenta Science EO2401: Enterome INO-5401+ INO-9012+ LIBTAYO (cemiplimab): Inovio Pharmaceuticals Selinexor (KPT-330): Karyopharm Therapeutics VBI-1901: VBI Vaccines NOX-A12 (Olaptesed Pegol): TME Pharma Tovorafenib (DAY101): Day One Biopharmaceuticals Vorasidenib (AG-881): Servier Eflornithine: Orbus Therapeutics TVI-Brain-1: TVAX Biomedical AB-218: AnHeart Therapeutics BGB-290: Beigene Mirdametinib: SpringWorks Therapeutics FT-2102 (Olutasidenib): Forma Therapeutics Vinblastine + Bevacizumab: Hoffmann-La Roche Cobimetinib: Hoffmann-La Roche PEMAZYRE (Pemigatinib): Incyte Corporation VERZENIO (abemaciclib): Eli Lilly Learn more about the FDA-approved drugs for glioma @ Drugs for Glioma Treatment Glioma Market Dynamics Glioma market growth can be ascribed to various factors, including an aging population, evolving research, better diagnostic tests, developing surgical procedures, improved radiotherapy techniques, and novel systemic medicines. Commercially, there is a greater emphasis on high-grade glioma than low-grade glioma because patients with low-grade glioma often live longer than those with high-grade glioma. As a result, just a few therapies are in late-stage studies, while the majority are in early-stage trials. In the case of GBM, on the other hand, the pipeline is robust, with numerous potential therapies in late and mid-stage research that have yet to be marketed. The pipeline includes drugs with varied modes of action and administration routes. It is interesting to note that the emerging market of glioma includes budding gene therapy, i.e., ofranergene obadenovec (VB-111) by VBL Therapeutics, followed by four vaccine/immunotherapy candidates such as VBI-1901, AV-GBM-1 and ITI-1000 (pp65 DC Vaccine), tasadenoturev (DNX-2401) by VBI Vaccines, Aivita Biomedical, Immunomic Therapeutics, and DNAtrix, respectively, and these therapies are going to alter the glioma market dynamics in the upcoming years. The current glioma market has been categorized based on the dominant treatment pattern across the 7MM, which shows slight variances in the overall prescription pattern. The forecast model considers surgery, chemotherapy/radiation therapy, bevacizumab + radiotherapy/chemotherapy, and OPTUNE with temozolomide. The anticipated launch of new therapies and improved integration of early patient screening, medication in secondary care and other clinical settings, research on optimum implementation methods, and increased awareness may eventually facilitate the development of successful treatment alternatives. However, there are a few challenges to the timely identification and treatment of these patients, such as a lack of a reliable biomarker that can aid in diagnosis and patient classification and identifying recurrence and signaling medication response. Furthermore, the failure rate of high-phased drug trials is significant, making it impossible to predict trial success, exacerbating the need for medicines that could assist ease the patient segment with this severe kind of cancer. Scope of the Glioma Market Report Therapeutic Assessment: Glioma current marketed and emerging therapies Glioma Market Dynamics: Conjoint Analysis of Emerging Glioma Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's Views, Analyst's Views, Glioma Market Access and Reimbursement Discover more about glioma drugs in development @ Glioma Clinical Trials Table to Contents Related Reports Glioma Epidemiology Forecast Glioma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted glioma epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Glioma Pipeline Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key glioma companies, including PTC Therapeutics, Ono Pharmaceuticals, Philogen, SpringWorks Therapeutics, Xennials Therapeutics, AnHeart Therapeutics, Istari Oncology, among others. High-Grade Glioma Pipeline High-Grade Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key high-grade glioma companies, including PTC Therapeutics, Aadi, Lee's Pharmaceutical, among others. Malignant Glioma Pipeline Malignant Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key malignant glioma companies, including Bexion Pharmaceuticals, Inc., Lee's Pharmaceutical Limited, Merck & Co, Oblato, Inc., OncoSynergy, Inc, among others. Recurrent Malignant Glioma Pipeline Recurrent Malignant Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key recurrent malignant glioma companies, including Bexion Pharmaceuticals, Inc., Merck, Oblato, OncoSynergy, Inc, among others. Glioblastoma Pipeline Glioblastoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key glioblastoma companies, including AstraZeneca, BioNTech, Merck, Pfizer, Roche, among others. 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It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

胰腺癌属致命恶性肿瘤之一，死亡率居世界第七位，主要分为胰腺导管腺癌（PDAC）和胰腺神经内分泌肿瘤。胰腺癌具有高度转移倾向，大部分患者诊断即为晚期，其化疗耐药性和特殊的肿瘤微环境会影响治疗效果，不可通过手术切除的局部晚期胰腺癌患者（LAPC）生存率小于5%。晚期常出现腹痛、恶心、中背痛、体重减轻、阻塞性黄疸、胃肠道 (GI) 出血、静脉血栓栓塞 (VTE)等相关症状。目前临床上针对LAPC患者常使用放化疗（CRT）结合吉西他滨等药物治疗，而转移性PDAC患者使用FOLFIRINOX（亚叶酸、5-氟尿嘧啶、伊立替康和奥沙利铂）能有效延长生存期。除了常规治疗手段，近来免疫疗法特别是溶瘤病毒疗法备受关注。近日，Frontiers in Oncology杂志刊登了题为《An Extensive Review on Preclinical and Clinical Trials of Oncolytic Viruses Therapy for Pancreatic Cancer》的研究综述，详细阐述了胰腺癌进展的分子机制以及总结了2000年以来已发表的溶瘤病毒疗法临床研究。胰腺癌细胞基因突变及分子机制研究发现，胰腺癌中大量聚集癌症干细胞（CSC），可能导致化疗耐药，肿瘤转移和复发，而产生CSC富集现象与上皮间充质转化（EMT）相关。针对各类胰腺癌进行全基因组测序分析，报告显示平均每个胰腺癌患者有63个突变，相关信号通路在大部分肿瘤中被阻断。“关于EMT-MET上皮细胞由于细胞黏附分子(如E-钙黏蛋白)表达减少、细胞角蛋白细胞骨架转化为波形蛋白（Vimentin）为主的细胞骨架，转变为间充质细胞，获得了较高的迁移与侵袭、抗凋亡和降解细胞外基质等能力。癌细胞在EMT激活后获得侵袭特性，从而导致癌细胞转移。当癌性间充质细胞到达（转移部位）时，会再次经历间充质-上皮转化 (MET)，以恢复上皮表型。miRNA失调MicroRNAs (miRNAs) 是小的非编码RNAs（20-25 nt），可调节靶mRNA的翻译。许多表达失调的miRNA与胰腺癌进展相关，如肿瘤转移、肿瘤耐药、癌症干性。过表达上调：过表达miR-301通过抑制胰腺癌细胞中E-cadherin的表达来调节EMT并导致吉西他滨耐药；过表达miR-296-5p靶向并下调BOK（凋亡调节基因），促进EMT、癌症侵袭和耐药性；过表达miR-103/107、miR-9、miR-181a促进EMT相关信号传导。干扰下调：胰腺癌细胞中Let-7和miR-200家族miRNA表达下调，抑制 Notch信号传导。在发现了 Let-7 和 miR-200 的下调；miR-148a、miR-141、miR-200家族、miR-216a、miR-217和miR-375等其他miRNA在胰腺癌中表达水平降低。K-Ras基因突变K-Ras蛋白是一种小GTPase转导蛋白，通过将外部信号传递到细胞核来调节细胞分裂。其在酪氨酸激酶激活后被激活，表皮生长因子 (EGF)与其受体结合，为表皮生长因子受体 (EGFR)。活化的K-Ras与GTP结合并通过MAPK和P13K/Akt引导的级联将活化信号转导到细胞核，从而调节细胞转化。致癌K-Ras基因突变使K-Ras因GTP水解被抑制而永久激活，导致对化学疗法产生抗性。在胰腺癌患者中，K-Ras基因突变高度发生且参与肿瘤形成发展，可作为重要治疗靶点。近日，一种直接共价靶向G12C突变体KRAS的策略揭示了潜在的动态药物结合位点，其他直接抑制K-Ras的基于结构的药物设计项目正在进行中。P13K信号通路磷脂酰肌醇3-激酶(PI3K)信号级联激活与生长因子刺激和细胞因子有关。细胞因子通过高亲和力细胞表面受体酪氨酸激酶(RTK)进入癌细胞，P13K下游信号通过进一步激活其他信号通路介导各种致癌功能，如癌细胞代谢、生长和运动。在PDAC和K-Ras构建的胰腺癌小鼠模型中P13K/Akt被激活，控制黏蛋白（MUC1）介导的放化疗法抗性。由此，MUC1-P13k信号的调节可作为胰腺癌的有效治疗靶点，使用P13K特异性抑制剂和下游信号分子衰减剂可尝试治疗PDAC患者。MAPK信号通路丝氨酸-苏氨酸激酶（MAPK），参与与各种细胞活动，如增殖、分化、转化和凋亡相关的细胞内信号传导，包括ERK（细胞外信号调节激酶）、JNK（c-Jun NH2-末端激酶）和p38。MAPK信号通路的中断显著加快了胰腺癌的进展。靶向MAPK信号下游基因可能使胰腺癌治疗效果提高。TGF-β信号通路转化生长因子-β（TGF-β）包含TGF- β、骨形态发生蛋白(BMP)和激活素/抑制素，调节细胞迁移、分化、增殖、凋亡和EMT等功能，在胰腺癌癌症初期通过阻止细胞周期进程和促进细胞凋亡表现肿瘤抑制特性，在癌症晚期阶段通过增强转移表达肿瘤促进特性。在靶向TGF-β的临床前试验中，与免疫检查点抑制剂联合使用时，靶向药物疗效改善。 缺氧信号通路在各种实体瘤中可以观察到缺氧介导的治疗抗性和生物学变化导致肿瘤转移率增加。肿瘤细胞通过刺激某些对氧敏感的信号通路进行反应，包括缺氧诱导因子1/2 (HIF1/2)信号通路和未折叠蛋白反应(UPR)，缺氧信号级联的变化导致新血管形成，最终导致肿瘤侵袭。胰腺癌中缺氧区域与不良预后和肿瘤发展有关，可作为胰腺癌恶性肿瘤的潜在治疗靶点。Wnt信号通路Wnt信号通路是一种进化保守的调控通路，包括非经典平面细胞极性(PCP)通路、非经典 Wnt/钙通路和经典通路，主要在细胞增殖、分化和存活中起作用。在胰腺癌中，该通路通过调节EMT、血管生成、细胞凋亡、干性和肿瘤微环境来促进癌变，瘤内经典Wnt配体过表达，通路持续激活也与胰腺癌耐药性有关。Notch信号通路Notch信号通过配体与Notch受体的结合而激活，显著促进细胞增殖、存活和分化。在癌症中，通过表达EMT标志物来促进细胞运动和侵袭特性，且会根据细胞环境发挥肿瘤抑制和致癌双重作用。胰腺癌中，Notch过表达，起致癌作用，信号通路的再激活也与胰腺癌的发生和进展有关，因此可作为胰腺癌有效生物标志物和治疗靶点。溶瘤病毒疗法癌症免疫疗法通过增强机体免疫系统识别和破坏癌细胞，溶瘤病毒（OVs）疗法作为一种新型的靶向免疫疗法，通过裂解作用选择性地消灭癌细胞，从而产生抗肿瘤免疫。由于肿瘤细胞内信号通路失调，使得病毒对异常的肿瘤细胞具有靶向选择性，而抗病毒信号传导的主要蛋白质编码基因突变导致的功能不完全丧失，有助于肿瘤细胞中的病毒复制，中断的信号传导也受到抑制以提高溶瘤病毒治疗的效果。研究表明，将相关信号通路抑制剂与溶瘤病毒协同作用，增强了病毒的细胞毒性，在癌症治疗中良好的临床治疗效果。（图为溶瘤病毒设计各通路靶点的应用汇总）腺病毒腺病毒是是非包膜双链DNA病毒，具有二十面体衣壳，55种血清型，通过柯萨奇和腺病毒受体（CAR）进入细胞。设计工程化腺病毒旨在提高抗肿瘤疗效和癌细胞选择性。临床前试验：① 溶瘤腺病毒Ad5/3-E2F-d24-vIL2使用具有携带Ad5型核酸和Ad3-Fiber的病毒基因组骨架，编码vIL-2、IL-2免疫调节变体蛋白。62%的小鼠模型显示出长期存活率以及免疫反应的激活。② 溶瘤腺病毒AdNuPAR-E-miR222-S外包被聚乙二醇化寡肽修饰的聚β-氨基酯，避免中和抗体产生，通过干扰miR-222在胰腺癌细胞中表达，有效控制了PANC-1肿瘤小鼠模型进展。③ 重组腺病毒DNX-2401易在具有缺陷P16 / RB / E2F通路的细胞中复制，有效抑制胰腺癌细胞系中肿瘤细胞的进展。在I期临床试验中显示针对脑癌的有效结果。临床试验：单纯疱疹病毒单纯疱疹病毒是包膜双链DNA病毒，具有二十面体衣壳，通过HVEM、nectin1、nectin2受体进入细胞，常用的工程化疱疹病毒有T-VEC, G207, HF10, HSV1716和OrienX010。临床前试验：① 具有突变ICP6基因的Myb34.5单纯疱疹病毒1型（HSV-1），在过表达β-myb基因的胰腺肿瘤细胞中显示有效的复制，与吉西他滨低剂量组合治疗小鼠模型，能够有效减小肿瘤大小。② 重组单纯疱疹病毒HSVGM-CS缺失3个基因（γ134.5，ICP47和ICP6），过表达GM-CSF。在基于胰腺癌细胞系的测试中发现，甲氨蝶呤（MTX）影响HSV-1在肿瘤细胞中的复制；5-氟尿嘧啶（5-FU），伊立替康（CPT-11），细胞因子如肿瘤坏死因子-α（TNF-α）与HSV-1联合用药改善了病毒复制并增加HSV-1的活性。临床试验：呼肠孤病毒呼肠孤病毒是非包膜分节段双链RNA病毒，对人体具有非致病性，通常选择性感染K-Ras、BRAF、EGFR突变的肿瘤细胞并复制。临床前试验：① 呼肠孤病毒（Reolysin）与硼替佐米（BZ）联合治疗胰腺癌，体外和体内测试发现增强了癌细胞凋亡，抗癌反应水平高。② 重组呼肠孤病毒rS1-mmGMCSF表达小鼠GM-CSF，临床前胰腺癌小鼠模型试验显示改善了免疫细胞（DC、 T细胞）全身抗肿瘤活性。③ 呼肠孤病毒与CD3-双特异性抗体（CD3-bsAbs）分别给药胰腺癌模型，病毒显著增强（CD3-bsAbs）抗肿瘤疗效，诱导了非注射远端病变的消退。临床试验：牛痘病毒牛痘病毒是包膜双链DNA病毒，设计工程化牛痘病毒增强胰腺癌细胞特异性裂解作用。临床前试验：① 牛痘病毒mpJX-594（mpJX）联合抗程序性死亡受体-1抗体（PD1）在小鼠胰腺神经内分泌肿瘤模型中提高抗肿瘤免疫反应，细胞凋亡水平增加，增殖减少。② 重组牛痘病毒VVL-21表达B5R和白细胞介素-21（IL-21）基因，在胰腺癌转移性小鼠和仓鼠模型中全身给药VVl-21与α程序性细胞死亡蛋白1（α-PD1），免疫细胞中CD8+T细胞、自然杀伤细胞和巨噬细胞活性水平增加。③ 重组牛痘病毒VV-ING4表达生长抑制剂ING4基因。在胰腺癌小鼠模型中测试VV-ING4单独使用发现其有效诱导癌细胞毒性和凋亡，与吉西他滨联合治疗中，VV-ING4改善吉西他滨抗癌疗效。④ 重组牛痘病毒vvdd-tdtomato-hGMCSF表达GMCSF基因，在免疫功能正常的仓鼠上测试，表达牛痘病毒的GMCSF有助于通过中性粒细胞和巨噬细胞的激活和侵袭完全清除皮下胰腺病变。临床试验：细小病毒细小病毒是非包膜单链DNA病毒，可降低胰腺癌细胞中IG和HERV的水平，减弱细胞先天免疫。临床前试验：① 腹膜转移的胰腺癌小鼠模型中，在肿瘤内注射H-1PV导致肿瘤减少，同时注射IFNγ，进一步改善了机体免疫反应。② 携带细胞趋化因子IL-2、MCP-3/CCL7和IP-10/CXCL10的细小病毒在胰腺癌异种移植中抗肿瘤疗效显著，表达IL-12的细小病毒比其他两种变体表现出更强的抗肿瘤反应。临床试验：麻疹病毒麻疹病毒是包膜单链负义RNA病毒，通过信号传导淋巴细胞活化分子（SLAM）受体或CD46受体进入细胞。临床前试验：① 重组麻疹病毒MeV-CD-FmiRTS148a表达5-氟胞嘧啶及前体，在胰腺癌异种移植模型中瘤内注射，治疗的小鼠显示出肿瘤大小减小，无进展生存期延长。少量MeV与吉西他滨联合给药，肿瘤体积减小大于50%。② 麻疹病毒MV-EGFPmtd编码miRTS（miR-122，miR-7和miR-148a），在体外和体内测试发现MV-EGFPmtd的高靶向胰腺癌细胞。水疱性口炎病毒水疱性口炎病毒是包膜非分段负义RNA病毒，优先在肿瘤细胞中感染复制。临床前试验：① 混合水疱性口炎病毒（VSV-FH）替换了麻疹病毒包膜蛋白F、H，通过突变K174E和E238K，降低了肿瘤对VSV的耐药性。② 重组VSV-ΔM51变异体通过下调IFN信号传导，并联合小分子抑制剂，显著消除了胰腺癌细胞中VSV耐药性。新城疫病毒新城疫病毒是包膜单链负义RNA病毒，通过病毒内吞作用或质膜融合进入细胞，对人类不具有致病性。因癌细胞过表达I型IFN、Bcl-xL和小GTPase，NDV选择性地在癌细胞中感染和复制。临床前试验：① 在小鼠低表达TGF-β模型中静脉注射NDV，发现肿瘤有效减少，无进展生存期延长。② 在异种移植模型肿瘤内注射rNDV-F3aa，显示肿瘤消退和抗肿瘤细胞毒性。小结溶瘤病毒疗法通过工程化插入外源基因或miRNA提高了胰腺癌治疗的有效性、特异性和安全性，特别是跟吉西他滨联合给药时，能显著降低吉西他滨的高剂量毒性，同时得到有效的临床结果。针对胰腺癌细胞中受损通路的有效靶点，设计特异的溶瘤病毒将是一种安全且有前景的治疗方式。（图为吉西他滨与重组或天然溶瘤病毒联合治疗相关的临床前研究汇总）