迈向肝癌个体化治疗。

IF 2.6 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Radhika Tippani, Pallavi Kagithoju, Ranjith Pabbati, Maheswara Reddy Mallu, Mahendar Porika
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引用次数: 0

摘要

由于缺乏适当的选择性治疗,肝细胞癌(HCC)仍然是癌症相关死亡的主要原因之一。慢性肝功能衰竭几乎总是伴随着HCC,医生通常只有在疾病发展到无法治愈的程度后才会发现它。尽管HCC具有不同的形态和表型模式,但治疗选择仅限于相对同质的药物,如多靶点酪氨酸激酶阻滞剂和免疫检查点阻滞剂。评估不同药物有效性的多项研究得出了令人失望的结果,表明HCC对化疗的免疫力较差,并因多药耐药而加剧。因此,需要更成功的治疗方法来解决HCC的紊乱代谢和分子途径。综合基因组图谱显示,HCC患者中经常发生的基因序列变化和分子靶点是端粒酶逆转录酶、Wnt/-catenin信号通路癌基因(CTNNB1)和TP53基因。此外,基因组尺度的代谢复制等新方法可以用来解释基本的癌症特异性代谢,从而探索有前途的生物标志物和候选药物。在氧化还原反应、代谢物使用和亚型特异性途径的基础上,代谢网络驱动hcccas2异质性的临床意义有助于加速个体化医疗的发展。另一个有趣的策略是基于microRNA的治疗,包括miRNA拮抗剂阻断致癌miRNA和miRNA替代,这需要重新引入肿瘤抑制miRNA来恢复功能损伤后的功能。本综述总结了分子靶点和基于代谢网络的方法的现有和不断发展的临床目的,为成功治疗HCC患者铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Towards a Personalized Medicine Approach for HCC.

Owing to the lack of appropriate selective treatments, hepatocellular carcinoma (HCC) remains one of the major reasons of cancer associated death. Chronic liver failure nearly always accompanies HCC, and doctors usually detect it only after the disease has progressed beyond the point where curative therapies are possible. Despite the fact that HCC has distinct morphological and phenotypic patterns, therapeutic options are limited to comparatively homogeneous drugs such as multi-targeted tyrosine kinase blockers and immune checkpoint blockers. Multiple studies evaluating the effectiveness of different medications have yielded disappointing findings, indicating that HCC has poor immunity to chemotherapy, which is exacerbated by multidrug resistance. As a result, more successful therapies addressing HCC's disordered metabolic and molecular pathways are needed. The quite often change in sequence of genes and molecular targets in HCC patients are telomerase reverse transcriptase, Wnt/-catenin signaling pathway oncogene (CTNNB1), and the TP53 gene, according to integrated genomic profiling. Furthermore, new approaches like genome-scale metabolic replicas may be utilized to explicate the basic cancer specific metabolism, allowing for such exploration of promising biomarkers and drug candidates. The clinical implications of metabolic network driven heterogeneity of HCCcaseson the basis of redox response, metabolite use, and subtype specific pathways could help accelerate the advancement of personalised medicine. Another interesting strategy is microRNA- based therapy which involves miRNA antagonists to block oncogenic miRNAs and miRNA substitution, which entails reintroducing a tumor-suppressor miRNA to restore function following a functional impairment. The existing and evolving clinical purpose in context of molecular targets and metabolic network-based approaches are summarised in this review, paving the way for successful HCC patient care.

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来源期刊
Current pharmaceutical biotechnology
Current pharmaceutical biotechnology 医学-生化与分子生物学
CiteScore
5.60
自引率
3.60%
发文量
203
审稿时长
6 months
期刊介绍: Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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