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Transforming treatment paradigms: Focus on personalized medicine for high-grade serous ovarian cancer. ​

文献信息 ​

DOI10.3322/caac.70008
PMID40252048
期刊CA: a cancer journal for clinicians
影响因子232.4
JCR 分区Q1
发表年份2025
被引次数4
关键词多样性，高级别浆液性卵巢癌，个性化医学，生活质量，治疗
文献类型Journal Article, Review
ISSN0007-9235
页码436-460
期号75(5)
作者Pawel Kordowitzki, Britta Lange, Kevin M Elias, Marcia C Haigis, Sylvia Mechsner, Ioana Elena Braicu, Jalid Sehouli

一句话小结 ​

本综述探讨了高级别浆液性卵巢癌（HGSOC）的复杂性，包括其病因、流行病学及治疗策略，强调其高基因拷贝数变化与DNA修复缺陷的关联。研究指出，理解HGSOC的分子基础和肿瘤微环境对开发靶向治疗及个性化治疗方案至关重要，并提倡将患者视角融入决策中，以改善患者生活质量。

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多样性 · 高级别浆液性卵巢癌 · 个性化医学 · 生活质量 · 治疗

摘要 ​

高级别浆液性卵巢癌（HGSOC）是卵巢癌中最常见且最具侵袭性的亚型，约占所有卵巢癌病例的70%，并显著导致与该疾病相关的高死亡率。由于早期疾病的无症状特性，大多数患者在癌症已扩散至腹腔的晚期阶段被诊断，这需要复杂且密集的外科及化学治疗干预，随后进行维持治疗。尽管少数病例与明确的遗传综合症相关，但在许多情况下，特定的风险因素和清晰的病因仍然难以捉摸。HGSOC肿瘤的特征是体细胞基因拷贝数改变的高频率，通常与DNA同源重组修复缺陷相关。迄今为止，所有尝试引入有效的HGSOC筛查的方法均未成功。本综述阐明了HGSOC的复杂性，涵盖其病因学、流行病学、分类、发病机制及当前的治疗策略。理解其分子基础对于开发靶向治疗和个性化多模式治疗方案在集中治疗结构中的重要性至关重要。本综述还探讨了肿瘤微环境的重要性。此外，作者的目标是强调将患者的视角和多样性置于治疗策略的首位的重要性，从而促进真正的参与式决策过程，最终改善患者的生活质量。

英文摘要 ​

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of all ovarian cancer cases and contributing significantly to the high mortality rates associated with this disease. Because of the asymptomatic nature of early stage disease, most patients are diagnosed at advanced stages when the cancer has already spread into the abdominal cavity, requiring complex and intensive surgical and chemotherapeutic interventions followed by maintenance therapies. Although a minority of cases are associated with well defined genetic syndromes, specific risk factors and a clear etiology in many cases remain elusive. HGSOC tumors are characterized by a high frequency of somatic gene copy number alterations, often associated with defects in homologous recombination repair of DNA. All attempts to introduce an effective screening for HGSOC to date have been unsuccessful. This review elucidates the complexities surrounding HGSOC and encompasses its etiology, epidemiology, classification, pathogenesis, and the current array of treatment strategies. Understanding molecular underpinnings is crucial for the development of targeted therapies and personalized multimodal treatment approaches in centralized therapeutic structures. This review also examines the importance of the tumor microenvironment. In addition, the authors' objective is to underscore the critical importance of placing the patient's perspective and diversity at the forefront of therapeutic strategies, thereby fostering a genuinely participatory decision-making process and ultimately improving patient quality of life.

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主要研究问题 ​

  1. 高级浆液性卵巢癌的个体化治疗策略有哪些具体的应用案例？
  2. 在高级浆液性卵巢癌的治疗中，如何评估患者的分子特征以制定个性化治疗方案？
  3. 目前有哪些新兴的靶向疗法在高级浆液性卵巢癌的临床试验中显示出希望？
  4. 高级浆液性卵巢癌的肿瘤微环境对治疗反应的影响是什么？
  5. 患者的参与和多样性如何在高级浆液性卵巢癌的治疗决策中得到更好的体现？

核心洞察 ​

研究背景和目的 ​

高等级浆液性卵巢癌（HGSOC）是卵巢癌中最常见且最具侵袭性的亚型，约占所有卵巢癌病例的70%，并显著影响患者的生存率。由于早期症状不明显，许多患者在疾病晚期被诊断，通常需要复杂的手术和化疗。因此，本研究旨在探讨HGSOC的病因、流行病学、分类、发病机制及现有治疗策略，强调个性化医学在HGSOC治疗中的重要性。

主要方法/材料/实验设计 ​

本研究为综述性文章，系统回顾了HGSOC的相关文献，分析了其分子机制及肿瘤微环境（TME）的影响，提出了个性化多模式治疗的必要性。研究的技术路线如下：

Mermaid diagram

关键结果和发现 ​

  1. HGSOC的病因：包括遗传因素（如BRCA1/2突变）、环境和生活方式因素（如肥胖、激素替代疗法等）。
  2. 分子特征：HGSOC通常伴随TP53突变及同源重组修复缺陷。
  3. 肿瘤微环境：癌相关成纤维细胞（CAFs）和肿瘤浸润淋巴细胞（TILs）对肿瘤的生长、转移和耐药性具有重要影响。
  4. 个性化治疗：强调将患者的多样性纳入治疗决策中，提出个性化治疗方案以改善患者的生活质量。

主要结论/意义/创新性 ​

本研究指出，HGSOC的治疗应从以肿瘤为中心转向以患者为中心，强调个性化医疗的重要性。通过综合考虑患者的遗传背景、生活方式及心理状态，制定更为精准的治疗方案，旨在提高治疗效果并改善患者的生活质量。

研究局限性和未来方向 ​

  1. 局限性：现有研究对不同种族和社会经济背景的患者代表性不足，影响了结果的普遍适用性。
  2. 未来方向：需进一步开展包括多样性患者的临床试验，探索新型靶向治疗和免疫疗法在HGSOC中的应用。同时，需加强对患者心理健康的关注，以支持患者在治疗过程中的心理需求。

本综述强调了在HGSOC治疗中整合个性化医学的必要性，未来的研究应致力于开发更加有效的治疗策略，并关注患者的整体福祉。

参考文献 ​

  1. High-grade serous ovarian carcinoma, the "Achiles' hill" for clinicians and molecular biologists: a molecular insight. - Rittwika Bhattacharya;Arijit Ghosh;Soma Mukhopadhyay - Molecular biology reports (2023)
  2. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. - Sandro Pignata;Giovanni Scambia;Gabriella Ferrandina;Antonella Savarese;Roberto Sorio;Enrico Breda;Vittorio Gebbia;Pietro Musso;Luigi Frigerio;Pietro Del Medico;Alessandra Vernaglia Lombardi;Antonio Febbraro;Paolo Scollo;Antonella Ferro;Stefano Tamberi;Alba Brandes;Alberto Ravaioli;Maria Rosaria Valerio;Enrico Aitini;Donato Natale;Laura Scaltriti;Stefano Greggi;Carmela Pisano;Domenica Lorusso;Vanda Salutari;Francesco Legge;Massimo Di Maio;Alessandro Morabito;Ciro Gallo;Francesco Perrone - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2011)
  3. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. - U Wagner;C Marth;R Largillier;J Kaern;C Brown;M Heywood;T Bonaventura;I Vergote;M C Piccirillo;R Fossati;V Gebski;E P Lauraine - British journal of cancer (2012)
  4. Epithelial-mesenchymal transition in ovarian cancer. - Daniele Vergara;Benjamin Merlot;Jean-Philippe Lucot;Pierre Collinet;Denis Vinatier;Isabelle Fournier;Michel Salzet - Cancer letters (2010)
  5. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. - I Ray-Coquard;A Leary;S Pignata;C Cropet;A González-Martín;C Marth;S Nagao;I Vergote;N Colombo;J Mäenpää;F Selle;J Sehouli;D Lorusso;E M Guerra Alia;G Bogner;H Yoshida;C Lefeuvre-Plesse;P Buderath;A M Mosconi;A Lortholary;A Burges;J Medioni;A El-Balat;M Rodrigues;T-W Park-Simon;C Dubot;D Denschlag;B You;E Pujade-Lauraine;P Harter; - Annals of oncology : official journal of the European Society for Medical Oncology (2023)
  6. Global epidemiology of epithelial ovarian cancer. - Penelope M Webb;Susan J Jordan - Nature reviews. Clinical oncology (2024)
  7. Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors. - Timothy A Yap;Brent O'Carrigan;Marina S Penney;Joline S Lim;Jessica S Brown;Maria J de Miguel Luken;Nina Tunariu;Raquel Perez-Lopez;Daniel Nava Rodrigues;Ruth Riisnaes;Ines Figueiredo;Suzanne Carreira;Brian Hare;Katherine McDermott;Saira Khalique;Chris T Williamson;Rachael Natrajan;Stephen J Pettitt;Christopher J Lord;Udai Banerji;John Pollard;Juanita Lopez;Johann S de Bono - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2020)
  8. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. - Michael A Bookman;Mark F Brady;William P McGuire;Peter G Harper;David S Alberts;Michael Friedlander;Nicoletta Colombo;Jeffrey M Fowler;Peter A Argenta;Koen De Geest;David G Mutch;Robert A Burger;Ann Marie Swart;Edward L Trimble;Chrisann Accario-Winslow;Lawrence M Roth - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2009)
  9. Transforming treatment paradigms: Focus on personalized medicine for high-grade serous ovarian cancer. - Pawel Kordowitzki;Britta Lange;Kevin M Elias;Marcia C Haigis;Sylvia Mechsner;Ioana Elena Braicu;Jalid Sehouli - CA: a cancer journal for clinicians (2025)
  10. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. - Sean Kehoe;Jane Hook;Matthew Nankivell;Gordon C Jayson;Henry Kitchener;Tito Lopes;David Luesley;Timothy Perren;Selina Bannoo;Monica Mascarenhas;Stephen Dobbs;Sharadah Essapen;Jeremy Twigg;Jonathan Herod;Glenn McCluggage;Mahesh Parmar;Ann-Marie Swart - Lancet (London, England) (2015)

引用本文的文献 ​

  1. Transforming treatment paradigms: Focus on personalized medicine for high-grade serous ovarian cancer. - Pawel Kordowitzki;Britta Lange;Kevin M Elias;Marcia C Haigis;Sylvia Mechsner;Ioana Elena Braicu;Jalid Sehouli - CA: a cancer journal for clinicians (2025)
  2. Ovarian Cancer-Epidemiology, Classification, Pathogenesis, Treatment, and Estrogen Receptors' Molecular Backgrounds. - Beata Smolarz;Karolina Biernacka;Honorata Łukasiewicz;Dariusz Samulak;Ewa Piekarska;Hanna Romanowicz;Marianna Makowska - International journal of molecular sciences (2025)
  3. Advances and obstacles of T cell-based immunotherapy in gynecological malignancies. - Xi Zhao;Jialing Ran;Shenglong Li;Jinxin Chen - Molecular cancer (2025)
  4. Dual-receptor PET imaging of ovarian cancer using a 68Ga-labeled heterodimer targeting folate receptor and HER2. - Xiaodan Shi;Zhangxin Wu;Yifeng Yuan;Ying Wang;Shuo Yang;Rong Li - American journal of nuclear medicine and molecular imaging (2025)

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