利用生态和进化动力学设计和改进卵巢癌治疗方法

IF 7.9 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Translational Medicine Pub Date : 2024-08-29 DOI:10.1002/ctm2.70012
Grace Y. Q. Han, Monica Alexander, Julia Gattozzi, Marilyn Day, Elayna Kirsch, Narges Tafreshi, Raafat Chalar, Soraya Rahni, Gabrielle Gossner, William Burke, Mehdi Damaghi
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引用次数: 0

摘要

卵巢癌的生态系统极其复杂,由高度异质性的癌细胞组成。多聚 ADP 核糖聚合酶(PARP)抑制剂、靶向疗法和免疫疗法等药物的开发为连续或联合治疗提供了更多选择。尽管如此,转移性卵巢癌患者的死亡率仍然居高不下,因为癌细胞对单一疗法和综合疗法不断产生抗药性,这就迫切需要针对癌细胞的进化性设计治疗方案。导致抗药性的进化动力来自复杂的肿瘤微环境、异质性群体以及单个癌细胞的可塑性。我们认为,要成功治疗卵巢癌,就必须考虑该疾病的生态和进化动态。在此,我们回顾了卵巢癌治疗的现有选择和挑战,并讨论了肿瘤进化的原理。最后,我们提出了针对卵巢癌的进化设计策略,目的是将这些原则与纵向定量数据相结合,改进治疗设计和耐药性管理。 要点/亮点 肿瘤是一个生态系统,癌细胞和非癌细胞在其中以复杂而动态的方式相互作用和进化。 卵巢癌的传统疗法由于未能考虑肿瘤的异质性和细胞可塑性,不可避免地会导致耐药性的产生。 生态进化设计的疗法应考虑到癌细胞的可塑性和患者的特异性,以改善临床疗效并防止复发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Ecological and evolutionary dynamics to design and improve ovarian cancer treatment

Ovarian cancer ecosystems are exceedingly complex, consisting of a high heterogeneity of cancer cells. Development of drugs such as poly ADP-ribose polymerase (PARP) inhibitors, targeted therapies and immunotherapies offer more options for sequential or combined treatments. Nevertheless, mortality in metastatic ovarian cancer patients remains high because cancer cells consistently develop resistance to single and combination therapies, urging a need for treatment designs that target the evolvability of cancer cells. The evolutionary dynamics that lead to resistance emerge from the complex tumour microenvironment, the heterogeneous populations, and the individual cancer cell's plasticity. We propose that successful management of ovarian cancer requires consideration of the ecological and evolutionary dynamics of the disease. Here, we review current options and challenges in ovarian cancer treatment and discuss principles of tumour evolution. We conclude by proposing evolutionarily designed strategies for ovarian cancer, with the goal of integrating such principles with longitudinal, quantitative data to improve the treatment design and management of drug resistance.

Key points/Highlights

  • Tumours are ecosystems in which cancer and non-cancer cells interact and evolve in complex and dynamic ways.

  • Conventional therapies for ovarian cancer inevitably lead to the development of resistance because they fail to consider tumours’ heterogeneity and cellular plasticity.

  • Eco-evolutionarily designed therapies should consider cancer cell plasticity and patient-specific characteristics to improve clinical outcome and prevent relapse.

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来源期刊
CiteScore
15.90
自引率
1.90%
发文量
450
审稿时长
4 weeks
期刊介绍: Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
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