Target and Gene-Based Therapeutic Strategies against Pancreatic Cancer: Current and Future Prospects.

IF 3.8 4区 医学 Q2 GENETICS & HEREDITY
Medha Dwivedi, Sayak Sanyal, Sakshi Singh, Manish Dwivedi, Somali Sanyal
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Abstract

Despite tremendous advancements in knowledge, diagnosis, and availability of both traditional and innovative treatments, pancreatic cancer remains a dangerous disease with a high death rate and dismal prognosis. The traditional strategy in adjuvant and palliative settings is still cytotoxic chemotherapy predicated on the purine derivative gemcitabine; nevertheless, there is an increasing need for new medicines that target the primary molecular pathways and pathophysiological abnormalities implicated. There is now just a tiny amount of evidence of therapeutic benefit when the targeted drug erlotinib is added to the conventional gemcitabine treatment. In preclinical and clinical trials, novel medications targeting mTOR, NF-κB, and proteasome, including the enzyme histone deacetylase, are currently being studied alongside the well-established monoclonal antibody treatments and small-molecule protein tyrosine kinase inhibitors. These novel medications may change the negative natural progression of this illness in conjunction with gene therapy and immunotherapy, both of which are undergoing clinical study. In this regard, leveraging miRNA manipulation to combat cancer is appealing due to its promise to deliver personalized treatment tailored to an individual's distinct gene or miRNA expression profile. Preclinical studies involving animals have showcased the effectiveness of miRNA-based therapies, with several of these treatments now progressing into human clinical trials for various malignancies and other medical conditions. This review describes the important developments of targeted therapeutics that are associated with pancreatic cancer and the discoveries which can help in dealing with this fatal malignancy in a more significant manner.

基于靶点和基因的胰腺癌治疗策略:当前和未来前景。
尽管在知识、诊断以及传统和创新治疗方法的可用性方面取得了巨大进步,但胰腺癌仍然是一种死亡率高、预后差的危险疾病。辅助治疗和姑息治疗的传统策略仍然是以嘌呤衍生物吉西他滨为基础的细胞毒性化疗;然而,针对主要分子通路和病理生理异常的新药需求与日俱增。目前,仅有极少量证据表明,在常规吉西他滨治疗的基础上加用靶向药物厄洛替尼可获得治疗效果。在临床前和临床试验中,针对 mTOR、NF-κB 和蛋白酶体(包括组蛋白去乙酰化酶)的新型药物目前正与成熟的单克隆抗体疗法和小分子蛋白酪氨酸激酶抑制剂一起进行研究。这些新型药物与正在进行临床研究的基因疗法和免疫疗法相结合,可能会改变这种疾病的消极自然发展过程。在这方面,利用 miRNA 操作来抗击癌症很有吸引力,因为它有望根据个人独特的基因或 miRNA 表达谱提供个性化治疗。涉及动物的临床前研究展示了基于 miRNA 的疗法的有效性,其中几种疗法现已进入针对各种恶性肿瘤和其他病症的人体临床试验阶段。本综述介绍了与胰腺癌相关的靶向疗法的重要发展,以及有助于更有效地治疗这种致命恶性肿瘤的发现。
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来源期刊
Current gene therapy
Current gene therapy 医学-遗传学
CiteScore
6.70
自引率
2.80%
发文量
46
期刊介绍: Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.
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