设计和改善卵巢癌治疗的生态和进化动力学
Ecological and evolutionary dynamics to design and improve ovarian cancer treatment
影响因子:6.80000
分区:医学2区 Top / 医学：研究与实验2区 肿瘤学2区
发表日期:2024 Sep
作者:
Grace Y Q Han, Monica Alexander, Julia Gattozzi, Marilyn Day, Elayna Kirsch, Narges Tafreshi, Raafat Chalar, Soraya Rahni, Gabrielle Gossner, William Burke, Mehdi Damaghi
摘要
卵巢癌生态系统非常复杂，包括癌细胞的高异质性。诸如聚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顺序或联合治疗提供了更多选择。然而，转移性卵巢癌患者的死亡率仍然很高，因为癌细胞始终对单一和联合疗法产生抗性，敦促需要针对癌细胞可增强性的治疗设计。从复杂的肿瘤微环境，异质种群和单个癌细胞的可塑性中出现了导致抵抗力的进化动力学。我们建议，成功管理卵巢癌需要考虑疾病的生态和进化动态。在这里，我们回顾了卵巢癌治疗中的当前选择和挑战，并讨论了肿瘤进化的原理。我们通过提出进化设计的卵巢癌策略来结束，目的是将这些原理与纵向，定量数据相结合，以改善耐药性的治疗设计和管理。关键点/亮点：肿瘤是生态系统，其中癌症和非癌细胞以复杂而动态的方式相互作用和发展。卵巢癌的常规疗法不可避免地会导致抗药性的发展，因为它们未能考虑肿瘤的异质性和细胞可塑性。生态进化设计的疗法应考虑癌细胞的可塑性和患者特异性特征，以改善临床结果并防止复发。
Abstract
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.