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黑色素瘤的异质性和分子特征:对靶向治疗的影响。

Heterogeneity and molecular landscape of melanoma: implications for targeted therapy.

机构信息

Laboratory of System Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

Software Engineering Department, Engineering Faculty, Istanbul Topkapi University, Istanbul, Turkey.

出版信息

Mol Biomed. 2024 May 10;5(1):17. doi: 10.1186/s43556-024-00182-2.


DOI:10.1186/s43556-024-00182-2
PMID:38724687
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11082128/
Abstract

Uveal cancer (UM) offers a complex molecular landscape characterized by substantial heterogeneity, both on the genetic and epigenetic levels. This heterogeneity plays a critical position in shaping the behavior and response to therapy for this uncommon ocular malignancy. Targeted treatments with gene-specific therapeutic molecules may prove useful in overcoming radiation resistance, however, the diverse molecular makeups of UM call for a patient-specific approach in therapy procedures. We need to understand the intricate molecular landscape of UM to develop targeted treatments customized to each patient's specific genetic mutations. One of the promising approaches is using liquid biopsies, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), for detecting and monitoring the disease at the early stages. These non-invasive methods can help us identify the most effective treatment strategies for each patient. Single-cellular is a brand-new analysis platform that gives treasured insights into diagnosis, prognosis, and remedy. The incorporation of this data with known clinical and genomics information will give a better understanding of the complicated molecular mechanisms that UM diseases exploit. In this review, we focused on the heterogeneity and molecular panorama of UM, and to achieve this goal, the authors conducted an exhaustive literature evaluation spanning 1998 to 2023, using keywords like "uveal melanoma, "heterogeneity". "Targeted therapies"," "CTCs," and "single-cellular analysis".

摘要

葡萄膜黑色素瘤(UM)具有复杂的分子特征,在遗传和表观遗传水平上均存在显著的异质性。这种异质性对塑造这种罕见眼部恶性肿瘤的行为和对治疗的反应起着关键作用。针对基因特异性治疗分子的靶向治疗可能有助于克服放射抵抗,但 UM 的多样化分子构成要求在治疗过程中采用个体化方法。我们需要了解 UM 的复杂分子特征,以开发针对每个患者特定基因突变的靶向治疗方法。一种很有前途的方法是使用液体活检,如循环肿瘤细胞(CTC)和循环肿瘤 DNA(ctDNA),在早期检测和监测疾病。这些非侵入性方法可以帮助我们确定每个患者最有效的治疗策略。单细胞是一个全新的分析平台,为诊断、预后和治疗提供了宝贵的见解。将这些数据与已知的临床和基因组学信息相结合,可以更好地了解 UM 疾病利用的复杂分子机制。在这篇综述中,我们重点关注 UM 的异质性和分子全景,为了实现这一目标,作者对 1998 年至 2023 年的文献进行了全面评估,使用了“葡萄膜黑色素瘤”、“异质性”、“靶向治疗”、“CTC”和“单细胞分析”等关键词。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/e7d6c43fca59/43556_2024_182_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/dbee45ddeeee/43556_2024_182_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/eaa1168e9e0b/43556_2024_182_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/4ebeee5dd58b/43556_2024_182_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/a0d8c63d63bb/43556_2024_182_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/e7d6c43fca59/43556_2024_182_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/dbee45ddeeee/43556_2024_182_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/eaa1168e9e0b/43556_2024_182_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/4ebeee5dd58b/43556_2024_182_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/a0d8c63d63bb/43556_2024_182_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b1c/11082128/e7d6c43fca59/43556_2024_182_Fig5_HTML.jpg

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引用本文的文献

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Advances in Materials Science for Precision Melanoma Therapy: Nanotechnology-Enhanced Drug Delivery Systems.

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[5]
[Disease burden and trend of melanoma among middle-aged and elderly population in China from 1990 to 2020, and prediction for 2022 to 2035].

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[6]
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[7]
[The concept of the liquid biopsy in the treatment of malignant eye tumours].

Ophthalmologie. 2024-12

[8]
Phenotyping Tumor Heterogeneity through Proteogenomics: Study Models and Challenges.

Int J Mol Sci. 2024-8-14

[9]
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Biomedicines. 2024-8-14

[10]
Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives.

Biomedicines. 2024-8-5

本文引用的文献

[1]
Integrating Single-cell and Bulk RNA-seq to Construct a Metastasis-related Model for Evaluating Immunotherapy and Chemotherapy in Uveal Melanoma.

Curr Med Chem. 2024

[2]
Recent approaches for the treatment of uveal melanoma: Opportunities and challenges.

Crit Rev Oncol Hematol. 2024-1

[3]
Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges.

Biomark Res. 2023-12-1

[4]
Single-cell characterization of macrophages in uveal melanoma uncovers transcriptionally heterogeneous subsets conferring poor prognosis and aggressive behavior.

Exp Mol Med. 2023-11

[5]
Decoding tumor heterogeneity in uveal melanoma: basement membrane genes as novel biomarkers and therapeutic targets revealed by multi-omics approaches for cancer immunotherapy.

Front Pharmacol. 2023-9-26

[6]
Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma.

Cell Rep. 2023-9-26

[7]
The immune checkpoint VISTA is associated with prognosis in patients with malignant uveal melanoma.

Front Immunol. 2023

[8]
Identification of co-expressed gene networks promoting CD8 T cell infiltration and having prognostic value in uveal melanoma.

BMC Ophthalmol. 2023-8-10

[9]
Effective methods for bulk RNA-seq deconvolution using scnRNA-seq transcriptomes.

Genome Biol. 2023-8-1

[10]
Radiotherapy in Uveal Melanoma: A Review of Ocular Complications.

Curr Oncol. 2023-7-3

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