Telomeres, which are situated at the terminal ends of chromosomes, undergo a reduction in length with each cellular division, ultimately reaching a critical threshold that triggers cellular senescence. Cancer cells circumvent this senescence by utilizing telomere maintenance mechanisms (TMMs) that grant them a form of immortality. These mechanisms can be categorized into two primary processes: the reactivation of telomerase reverse transcriptase and the alternative lengthening of telomeres (ALT) pathway, which is dependent on homologous recombination (HR). Various strategies have been developed to inhibit telomerase activation in 85-95% of cancers, including the use of antisense oligonucleotides such as small interfering RNAs and endogenous microRNAs, agents that simulate telomere uncapping, expression modulators, immunotherapeutic vaccines targeting telomerase, reverse transcriptase inhibitors, stabilization of G-quadruplex structures, and gene therapy approaches. Conversely, in the remaining 5-15% of human cancers that rely on ALT, mechanisms involve modifications in the chromatin environment surrounding telomeres, upregulation of TERRA long non-coding RNA, enhanced activation of the ataxia telangiectasia and Rad-3-related protein kinase signaling pathway, increased interactions with nuclear receptors, telomere repositioning driven by HR, and recombination events between non-sister chromatids, all of which present potential targets for therapeutic intervention. Additionally, combinatorial therapy has emerged as a strategy that employs selective agents to simultaneously target both telomerase and ALT, aiming for optimal clinical outcomes. Given the critical role of anti-TMM strategies in cancer treatment, this review provides an overview of the latest insights into the structure and function of telomeres, their involvement in tumorigenesis, and the advancements in TMM-based cancer therapies.

Zahra Sadr

Masoumeh Ghasemi

Soheyla Jafarpour

Reyhaneh Seyfi

Aida Ghasemi

Elham Boustanipour

Hamid Reza Khorram Khorshid

Naeim Ehtesham

Molecular Genetics and Genomics

分子遗传学和基因组学 (MGG) 发表同行评议的文章，涵盖遗传学和基因组学的所有领域。任何研究基因和基因组的方法都被考虑在内，无论是实验的、理论的还是合成的。 MGG 发表对遗传学、基因组学、生物学、医学和生物技术领域工作人员广泛感兴趣的所有生物的研究。该杂志调查了广泛的主题，包括最近几期的主题：延长寿命的机制生物体；筛选涉及线粒体功能的酵母金属稳态基因；稻瘟病菌品种特异性无毒基因的分子作图等。

Molecular Genetics and Genomics (MGG) publishes peer-reviewed articles covering all areas of genetics and genomics. We welcome any research methods related to genes and genomes, whether experimental, theoretical, or synthetic. The research published in this journal is of broad interest to professionals in genetics, genomics, biology, medicine, and biotechnology. The topics we explore are diverse, including recent themes such as mechanisms of lifespan extension; screening of yeast metal homeostasis genes involved in mitochondrial function; and molecular mapping of variety-specific avirulence genes in rice blast fungus.

《Molecular Genetics and Genomics》是一本发表同行评审文章的期刊，涵盖遗传学和基因组学的各个领域。我们欢迎任何研究基因和基因组的方法，无论是实验性的、理论性的还是合成性的。该期刊发表的研究对遗传学、基因组学、生物学、医学和生物技术领域的专业人士具有广泛的吸引力。我们探讨的主题范围广泛，包括最近几期的研究：延长寿命的机制；筛选与线粒体功能相关的酵母金属稳态基因；以及稻瘟病菌品种特异性无毒基因的分子作图等。

Category	Quartile
生物学	3
生物学, 生化与分子生物学	3
生物学, 遗传学	3

Beginning at the ends: telomere and telomere-based cancer therapeutics

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Journal Info

Category	Quartile
GENETICS & HEREDITY	3