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通过综合方法和氨基酸代谢来解析和靶向血液系统恶性肿瘤中的致癌途径。

Deciphering and targeting oncogenic pathways through integrated approaches and amino acid metabolism in hematologic malignancies.

作者信息

Ikhtiar Farhan, Jamal Adil, Bokhari Syed M Safeer Mehdi

机构信息

University of Central Punjab, Lahore, Pakistan.

The University of Faisalabad, Faisalabad, Pakistan.

出版信息

Discov Oncol. 2025 Sep 16;16(1):1687. doi: 10.1007/s12672-025-03535-7.

Abstract

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, represent a diverse group of blood cancers driven by complex oncogenic pathways and genetic aberrations. Despite advances in treatment, resistance and relapse remain significant clinical challenges. This review presents an integrative approach to blood cancer therapy, highlighting the convergence of precision medicine, CRISPR-based gene editing, immunotherapy (including CAR-T cells and immune checkpoint inhibitors), and targeted modulation of amino acid metabolism. We investigate the molecular pathways driving tumour development and resistance, highlighting how multi-omic profiling facilitates personalised therapy approaches. Recent breakthroughs in reprogramming immune responses and editing driver mutations have revolutionized therapeutic paradigms. Additionally, the metabolic dependencies of cancer cells, particularly in amino acid biosynthesis and catabolism, offer novel vulnerabilities. This meticulous synthesis outlines a framework for translational techniques that integrate molecular targeting with immunological and metabolic regulation to improve treatment effectiveness and surmount therapeutic resistance in haematologic malignancies.

摘要

血液系统恶性肿瘤,包括白血病、淋巴瘤和多发性骨髓瘤,是由复杂的致癌途径和基因畸变驱动的多种血液癌症。尽管治疗取得了进展,但耐药性和复发仍然是重大的临床挑战。本综述提出了一种血液癌症治疗的综合方法,强调了精准医学、基于CRISPR的基因编辑、免疫疗法(包括嵌合抗原受体T细胞和免疫检查点抑制剂)以及氨基酸代谢的靶向调节的融合。我们研究了驱动肿瘤发展和耐药性的分子途径,强调了多组学分析如何促进个性化治疗方法。在重新编程免疫反应和编辑驱动突变方面的最新突破彻底改变了治疗模式。此外,癌细胞的代谢依赖性,特别是在氨基酸生物合成和分解代谢方面,提供了新的脆弱点。这种精心的综合概述了一个转化技术框架,该框架将分子靶向与免疫和代谢调节相结合,以提高血液系统恶性肿瘤的治疗效果并克服治疗耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8520/12440852/b013ec1e78d4/12672_2025_3535_Fig1_HTML.jpg

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