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

Literature Information ​

DOI10.3322/caac.70008
PMID40252048
JournalCA: a cancer journal for clinicians
Impact Factor232.4
JCR QuartileQ1
Publication Year2025
Times Cited4
Keywordsdiversity, high‐grade serous ovarian cancer, personalized medicine, quality of life, treatment
Literature TypeJournal Article, Review
ISSN0007-9235
Pages436-460
Issue75(5)
AuthorsPawel Kordowitzki, Britta Lange, Kevin M Elias, Marcia C Haigis, Sylvia Mechsner, Ioana Elena Braicu, Jalid Sehouli

TL;DR ​

This review highlights the complexities of high-grade serous ovarian cancer (HGSOC), the most prevalent and aggressive subtype, which is often diagnosed at advanced stages due to asymptomatic early disease. The authors emphasize the need for a deeper understanding of its molecular mechanisms and the tumor microenvironment to inform targeted therapies, while advocating for patient-centered approaches to improve treatment outcomes and quality of life.

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diversity · high‐grade serous ovarian cancer · personalized medicine · quality of life · treatment

Abstract ​

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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Primary Questions Addressed ​

  1. What are the latest advancements in personalized medicine specifically for high-grade serous ovarian cancer?
  2. How do genetic variations among patients influence the effectiveness of targeted therapies in high-grade serous ovarian cancer?
  3. What role does the tumor microenvironment play in the progression and treatment response of high-grade serous ovarian cancer?
  4. How can patient diversity and perspectives be effectively integrated into the development of treatment strategies for high-grade serous ovarian cancer?
  5. What are the challenges and potential solutions for implementing personalized multimodal treatment approaches in clinical practice for high-grade serous ovarian cancer?

Key Findings ​

Research Background and Purpose ​

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive subtype of ovarian cancer, responsible for approximately 70% of cases and associated with high mortality rates. Due to its asymptomatic early stages, most patients are diagnosed at advanced stages, complicating treatment. This review aims to elucidate the complexities surrounding HGSOC, including its etiology, epidemiology, classification, pathogenesis, and current treatment strategies, while emphasizing the importance of personalized medicine and patient-centered approaches in improving outcomes and quality of life.

Main Methods/Materials/Experimental Design ​

The review synthesizes existing literature on HGSOC, integrating findings from various studies on its molecular underpinnings, treatment strategies, and the tumor microenvironment (TME). A focus is placed on personalized medicine, incorporating patient diversity and preferences into treatment decision-making.

Mermaid diagram

Key Results and Findings ​

  1. Epidemiology: HGSOC primarily affects women aged 55-64, with significant geographic and racial disparities in incidence and survival rates.
  2. Pathogenesis: Most HGSOC tumors originate from the fallopian tube epithelium, with common genetic alterations, including TP53 mutations and BRCA1/BRCA2 deficiencies, contributing to tumorigenesis.
  3. Treatment Strategies: Current treatments involve aggressive surgical cytoreduction followed by chemotherapy. Emerging therapies include PARP inhibitors and immunotherapies, showing promise in improving outcomes for specific patient groups.
  4. Patient-Centered Care: Emphasizing the integration of patient preferences and psychological support into treatment plans can enhance adherence and improve quality of life.

Main Conclusions/Significance/Innovation ​

The review advocates for a paradigm shift towards personalized medicine in HGSOC treatment, emphasizing the need for a multidisciplinary approach that incorporates patient diversity and preferences. By understanding the molecular and environmental factors influencing HGSOC, healthcare providers can develop more effective, tailored therapeutic strategies, ultimately improving survival rates and quality of life for patients.

Research Limitations and Future Directions ​

  • Limitations: The review highlights the lack of comprehensive genetic testing accessibility for minority groups and the need for more inclusive clinical trials to ensure equitable treatment options.
  • Future Directions: Emphasis on further research into the molecular characterization of HGSOC, exploration of new therapeutic agents, and the development of supportive care strategies to manage the psychological and physical burdens of the disease. The integration of patient-reported outcomes and quality of life measures into routine clinical practice is essential for optimizing care.

Summary Table of Key Points ​

AspectDetails
EpidemiologyIncidence peaks in women aged 55-64; significant disparities exist.
PathogenesisOriginates from fallopian tube epithelium; TP53 and BRCA mutations common.
Current TreatmentsSurgical cytoreduction, chemotherapy, PARP inhibitors, immunotherapy.
Patient-Centered CareImportance of integrating patient preferences and psychological support.
Future ResearchFocus on molecular characterization, inclusive clinical trials, and QoL measures.

References ​

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  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)
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Literatures Citing This Work ​

  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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