Review

生态与进化动力学在卵巢癌治疗设计与优化中的应用

Ecological and evolutionary dynamics to design and improve ovarian cancer treatment

Clinical and Translational Medicine

影响因子:6.8

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

DOI: 10.1002/ctm2.70012

摘要

卵巢癌生态系统极其复杂，由高度异质的癌细胞组成。多巴胺聚合酶（PARP）抑制剂、靶向治疗和免疫治疗等药物的发展为连续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，因为癌细胞不断发展出对单一和联合疗法的耐药性，促使我们需要设计能够针对癌细胞进化潜能的治疗策略。耐药性的出现源于复杂的肿瘤微环境、多样化的细胞群体以及癌细胞的可塑性。我们提出，成功管理卵巢癌需要考虑肿瘤的生态与进化动力学。本文回顾了卵巢癌的现有治疗方案与挑战，并讨论了肿瘤进化的基本原则。最后，提出了利用进化学设计的策略，旨在结合纵向、定量数据，优化治疗方案和药物耐药的管理。重点内容包括：肿瘤是一个生态系统，癌细胞与非癌细胞相互作用并以复杂动态的方式演化；传统治疗未能考虑肿瘤的异质性和细胞可塑性，易导致耐药；生态-进化设计的治疗策略应考虑癌细胞的可塑性和患者特异性特征，以改善临床结果并预防复发。

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.