Virtual Research Center for Ovarian Cancer - VRCOC

30/08/2025

https://scienceon.kisti.re.kr/srch/selectPORSrchReport.do?cn=TRKO202100017841

□ 연구개요본 연구에서는 인공지능 및 딥러닝 기법을 활용하여 다양한 암종에서 대규모 유전체 데이터 분석을 수행함. 이를 통해 driver mutation 등 암 발생 관련 주요 인자 및 암에서의 기능적 모듈을 탐색하고, 향후 유전체 정보...

20/08/2025

■ Here are the targeted drugs currently available for ovarian cancer:

# # PARP Inhibitors (Most Important Class)

**Olaparib (Lynparza)**
- **Target**: PARP1/PARP2 enzymes
- **Mechanism**: Exploits synthetic lethality in BRCA-deficient tumors by preventing DNA repair
- **Current Indications**: First-line maintenance in BRCA-mutated and HRD-positive advanced ovarian cancer
- **Biomarker**: BRCA1/2 mutations, homologous recombination deficiency (HRD)

**Niraparib (Zejula)**
- **Target**: PARP1/PARP2 enzymes
- **Mechanism**: Similar DNA repair pathway targeting
- **Indications**: Maintenance therapy following response to platinum-based chemotherapy
- **Note**: Can be used regardless of BRCA status in certain settings

**Rucaparib (Rubraca)**
- **Target**: PARP1/PARP2 enzymes
- **Mechanism**: DNA repair pathway inhibition
- **Status**: Approved for 2nd or greater line maintenance following response to platinum-based chemotherapy for recurrent platinum-sensitive ovarian cancer
- **Note**: Some advanced ovarian cancer indications were withdrawn as of March 26, 2024

# # Antibody-Drug Conjugates (ADCs)

**Mirvetuximab Soravtansine (Elahere)**
- **Target**: Folate receptor alpha (FRα)
- **Mechanism**: Antibody-drug conjugate comprising an FRα-binding antibody attached via a cleavable linker to the maytansinoid DM4 payload, a potent microtubule inhibitor
- **Indications**: Advanced, platinum-resistant ovarian cancer whose tumors produce an excessive amount of FR-α protein. About 80% of people with high-grade serous epithelial ovarian cancer have tumors that overexpress this target
- **Biomarker**: FRα expression by immunohistochemistry

**Trastuzumab Deruxtecan (Enhertu)**
- **Target**: HER2 receptor
- **Mechanism**: HER2-targeting antibody-drug conjugate
- **Indications**: New targeted therapy option for people with HER2+ tumors (IHC 3+ or 2+)
- **Biomarker**: HER2 overexpression by IHC

# # Anti-Angiogenic Agents

**Bevacizumab (Avastin)**
- **Target**: VEGF (vascular endothelial growth factor)
- **Mechanism**: Blocks a growth factor that makes blood vessels. By blocking VEGF, some cancers can be starved of food and oxygen
- **Applications**: Has been shown to shrink or slow the growth of advanced epithelial ovarian cancers and appears to work even better when given along with chemotherapy
- **Combination Use**: Added as category 2A recommendation combined with mirvetuximab soravtansine for platinum-resistant, FRα-expressing tumors

# # Important Clinical Updates

There have been 9 FDA PARP inhibitor approvals/indications in ovarian cancer since 2014, though some have been withdrawn due to updated risk-benefit assessments.

The field is rapidly evolving with combination approaches, such as PARP inhibitors (niraparib, olaparib, and veliparib) being tested as initial treatment for newly diagnosed advanced ovarian cancer.

**Required Biomarker Testing**:
- BRCA1/2 mutation testing for PARP inhibitor eligibility
- HRD testing for expanded PARP inhibitor use
- FRα expression testing for mirvetuximab soravtansine
- HER2 testing for trastuzumab deruxtecan

These targeted therapies represent a shift from traditional chemotherapy to precision medicine approaches based on specific molecular vulnerabilities in ovarian cancer tumors.

20/08/2025

■ Ovarian Cancer: Molecular Pathophysiology to Clinical Symptoms Knowledge Graph


This knowledge graph framework connects molecular-level mechanisms with clinical manifestations in ovarian cancer, providing a holistic understanding of disease progression from cellular dysfunction to patient symptoms.

# # 1. Molecular Foundation Layer

# # # Key Genetic Alterations
- **BRCA1/BRCA2 mutations** → DNA repair deficiency → genomic instability
- **TP53 mutations** (90% of high-grade serous carcinomas) → cell cycle dysregulation
- **PTEN loss** → PI3K/AKT pathway activation → increased cell survival
- **PIK3CA mutations** → enhanced proliferation signals
- **Homologous recombination deficiency (HRD)** → DNA damage accumulation

# # # Signaling Pathway Dysregulation
- **PI3K/AKT/mTOR pathway** → increased cell growth and metabolism
- **VEGF signaling** → enhanced angiogenesis
- **Wnt/β-catenin pathway** → altered cell adhesion and migration
- **NF-κB activation** → inflammation and survival signals
- **p53 pathway disruption** → loss of apoptosis control

# # 2. Cellular Pathophysiology Layer

# # # Tumor Microenvironment Changes
- **Cancer-associated fibroblasts (CAFs)** → extracellular matrix remodeling
- **Tumor-associated macrophages (TAMs)** → immune suppression
- **Angiogenesis dysregulation** → abnormal blood vessel formation
- **Hypoxia signaling** → metabolic reprogramming

# # # Cellular Dysfunction
- **Epithelial-mesenchymal transition (EMT)** → increased invasiveness
- **Metabolic reprogramming** → altered glucose and lipid metabolism
- **Apoptosis resistance** → tumor cell survival
- **DNA damage response failure** → mutation accumulation

# # 3. Tissue-Level Pathophysiology

# # # Local Tumor Effects
- **Ovarian capsule distension** → ovarian enlargement
- **Peritoneal seeding** → intraperitoneal tumor spread
- **Ascites formation** → fluid accumulation from:
- Increased vascular permeability (VEGF)
- Lymphatic obstruction
- Altered oncotic pressure

# # # Organ System Impact
- **Bowel involvement** → mechanical obstruction
- **Bladder compression** → urinary symptoms
- **Vascular invasion** → metastatic spread
- **Lymphatic involvement** → regional spread

# # 4. Clinical Symptom Manifestation

# # # Early-Stage Symptoms (Often Subtle)
**Molecular → Clinical Connections:**
- Hormonal disruption → menstrual irregularities
- Early peritoneal irritation → vague pelvic discomfort
- Metabolic changes → fatigue
- Small volume ascites → subtle abdominal bloating

# # # Advanced-Stage Symptoms
**Direct Molecular-Clinical Links:**

# # # # Abdominal Symptoms
- **VEGF-driven ascites** → abdominal distension, early satiety
- **Peritoneal carcinomatosis** → abdominal pain, bowel obstruction
- **Metabolic dysregulation** → nausea, appetite changes

# # # # Systemic Symptoms
- **Inflammatory cytokines (TNF-α, IL-6)** → fatigue, weight loss
- **Paraneoplastic effects** → various systemic manifestations
- **Tumor burden** → performance status decline

# # # # Mechanical Symptoms
- **Pelvic mass effect** → urinary frequency, pelvic pressure
- **Bowel involvement** → constipation, intestinal obstruction
- **Lymphatic obstruction** → lower extremity edema

# # 5. Knowledge Graph Connections

# # # Multi-Level Relationships

```
BRCA1/2 Mutation
↓
Homologous Recombination Deficiency
↓
DNA Damage Accumulation
↓
Genomic Instability
↓
Tumor Heterogeneity
↓
Treatment Resistance
↓
Clinical Progression
```

# # # Pathway Convergence Points
- **p53 Hub**: Multiple molecular alterations converge on p53 dysfunction
- **VEGF Node**: Connects angiogenesis, ascites, and abdominal symptoms
- **Inflammation Network**: Links tumor microenvironment to systemic symptoms
- **Metabolic Hub**: Connects cellular energetics to clinical cachexia

# # 6. Clinical Applications

# # # Biomarker Development
- **CA-125 elevation** ← MUC16 overexpression ← transcriptional dysregulation
- **HE4 (WFDC2)** ← protease inhibitor dysregulation
- **Circulating tumor DNA** ← genomic instability and cell death

# # # Therapeutic Targeting
- **PARP inhibitors** → exploit HRD → synthetic lethality
- **Bevacizumab** → target VEGF → reduce ascites and angiogenesis
- **Immunotherapy** → target immune suppression mechanisms

# # # Prognostic Stratification
- **Molecular subtypes** → predict clinical behavior
- **Mutational signatures** → guide treatment selection
- **Tumor microenvironment profiles** → assess immune response

# # 7. Integrated Disease Model

# # # Temporal Progression
1. **Initiation**: Genetic alterations in fallopian tube epithelium
2. **Promotion**: Microenvironment changes and immune evasion
3. **Progression**: Local invasion and peritoneal seeding
4. **Metastasis**: Distant organ involvement
5. **Clinical manifestation**: Symptom development and diagnosis

# # # Feedback Loops
- **Hypoxia** → VEGF production → angiogenesis → tumor growth → more hypoxia
- **Inflammation** → tissue damage → more inflammation → tumor promotion
- **Metabolic stress** → adaptation mechanisms → enhanced survival

# # 8. Personalized Medicine Integration

# # # Patient Stratification
- **Germline testing** → hereditary risk assessment
- **Tumor genomics** → therapeutic vulnerability identification
- **Immune profiling** → immunotherapy candidacy

# # # Treatment Selection
- **Molecular signatures** → drug sensitivity prediction
- **Pathway analysis** → combination therapy design
- **Resistance mechanisms** → treatment sequencing

# # Conclusion

This knowledge graph framework demonstrates how ovarian cancer progresses from molecular alterations through cellular dysfunction to clinical symptoms. Understanding these connections enables:

- **Earlier detection** through symptom pattern recognition
- **Precision therapeutics** targeting specific molecular vulnerabilities
- **Improved prognostic models** integrating multi-level data
- **Rational drug development** based on mechanistic understanding

The holistic view provided by this molecular-to-clinical mapping is essential for advancing ovarian cancer care from reactive treatment to predictive, preventive, and personalized medicine.

14/02/2025

AI가 작성한 미니 메타분석 논문

■ Title ; Efficacy and Safety of Maintenance Therapies in Ovarian Cancer: A Meta-Analysis of Recent Randomized Controlled Trials

**Abstract**

This meta-analysis evaluates the efficacy and safety of maintenance therapies in ovarian cancer, focusing on studies published in the past five years. A systematic search identified randomized controlled trials (RCTs) assessing maintenance treatments such as poly(ADP-ribose) polymerase inhibitors (PARPis) and anti-angiogenic agents. The primary outcome was progression-free survival (PFS), with secondary outcomes including overall survival (OS) and treatment-related adverse events (AEs). The analysis indicates that maintenance therapies, particularly PARPis, significantly improve PFS in patients with ovarian cancer, regardless of BRCA mutation or homologous recombination deficiency (HRD) status. However, these therapies are associated with an increased risk of AEs, necessitating careful patient monitoring.

**Introduction**

Ovarian cancer remains a leading cause of gynecologic cancer mortality worldwide. Despite initial responsiveness to platinum-based chemotherapy, the majority of patients experience disease recurrence. Maintenance therapy has emerged as a strategy to prolong remission and improve survival outcomes. Recent years have seen the development of targeted agents, notably PARPis and anti-angiogenic drugs, as maintenance treatments. This meta-analysis aims to synthesize the latest evidence from RCTs published in the past five years to assess the efficacy and safety of these maintenance therapies.

**Methods**

A comprehensive literature search was conducted using databases such as PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science to identify RCTs published between February 14, 2020, and February 14, 2025. Studies were included if they evaluated maintenance therapies in ovarian cancer and reported outcomes on PFS, OS, and AEs. Data extraction and quality assessment were performed independently by two reviewers. Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model.

**Results**

The search identified multiple RCTs evaluating PARPis and anti-angiogenic agents as maintenance therapies. PARPis were associated with a significant improvement in PFS (HR = 0.53, 95% CI 0.40–0.71; P < 0.0001). This benefit was observed not only in patients with BRCA mutations (HR = 0.35, 95% CI 0.29–0.42; P < 0.00001) and HRD (HR = 0.43, 95% CI 0.32–0.60; P < 0.00001) but also in those with non-mutated BRCA (HR = 0.72, 95% CI 0.63–0.82; P < 0.00001) and even non-HRD (HR = 0.83, 95% CI 0.70–0.99; P = 0.04) citeturn0search0. However, maintenance therapy was associated with an increased incidence of AEs, including nausea, vomiting, diarrhea, fatigue, and hypertension, which required dose reductions citeturn0search2.

**Discussion**

The findings suggest that maintenance therapy with PARPis offers a significant PFS benefit across various patient subgroups, including those without BRCA mutations or HRD. However, the increased risk of AEs highlights the importance of vigilant monitoring and management during treatment. Further research is needed to optimize patient selection and manage AEs effectively.

**Conclusion**

Maintenance therapies, particularly PARPis, significantly improve PFS in ovarian cancer patients, irrespective of BRCA or HRD status. Clinicians should weigh the benefits against the potential for increased AEs and tailor treatment plans accordingly.

**References**

1. [PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta-analysis](https://pubmed.ncbi.nlm.nih.gov/32654312/)

2. [Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives – a review](https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-019-0579-0)

3. [Maintenance Therapy in Ovarian Cancer with Targeted Agents Improves PFS and OS: A Systematic Review and Meta-Analysis](https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0139026)

4. [Comparative efficacy of targeted maintenance therapy for newly diagnosed epithelial ovarian cancer: a network meta-analysis](https://pubmed.ncbi.nlm.nih.gov/31190984/)

5. [Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials](https://pubmed.ncbi.nlm.nih.gov/32117564/)

6. [Comparative Efficacy and Safety of PARP Inhibitors as Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis](https://pubmed.ncbi.nlm.nih.gov/33692936/)

PARPis provide a significant PFS benefit as first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.

10/11/2024

#난소암 #면역치료

Karoline Strauss was filled with dread after she was diagnosed with stage IIIc ovarian cancer. Today, she has much smaller tumors and hope, thanks to an immunotherapy clinical trial she found at MD Anderson and her care team.

27/09/2023

http://www.docdocdoc.co.kr/news/articleView.html?idxno=2005118

"올라파립는 높은 재발률과 치사율로 난제였던 진행성 난소암에 있어 정밀의료의 가치와 유지요법이라는 새로운 치료영역을 개척한 치료제다. 재발을 반복할수록 무병생존기간이 짧아지는 난소암에서 재발을...

26/09/2023

http://www.bosa.co.kr/news/articleView.html?idxno=2206405

[의학신문·일간보사=오인규 기자] 비트컴퓨터(대표 조현정·전진옥)는 ‘바로닥터(Baro Doctor)’를 서비스한다고 25일 밝혔다.‘바로닥터’는 EMR(전자의무기록)과 연동한 비대면 진료 플랫폼이다. 기존 비대면...

16/04/2023

https://link.springer.com/article/10.1007/s10555-022-10075-x

Cancer is one of the three leading causes of death worldwide. Even after successful therapy and achieving remission, the risk of relapse often remains. In this context, dormant residual cancer cells in secondary organs such as the bone marrow constitute the cellular reservoir from which late tumor r...

16/04/2023

https://www.nature.com/articles/s41417-023-00589-z/tables/1

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the si...

23/03/2023

난소암의 분자 유전적 기전은 무엇입니까?

난소암은 발병과 관련된 많은 분자 유전적 메커니즘을 가진 복잡한 질병입니다. 다음은 난소암과 관련된 주요 유전적 메커니즘 중 일부입니다.

종양 억제 유전자의 돌연변이: 종양 억제 유전자는 세포 성장과 분열을 조절하여 암을 예방하는 데 도움이 되는 유전자입니다. 이러한 유전자의 돌연변이는 제어되지 않은 세포 성장 및 분열을 유발하여 난소암 발병에 기여할 수 있습니다. 난소암에서 일반적으로 변이되는 종양 억제 유전자의 예로는 TP53, BRCA1 및 BRCA2가 있습니다.

발암 유전자의 돌연변이: 발암 유전자는 세포 성장과 분열을 촉진하는 유전자입니다. 이 유전자의 돌연변이는 유전자를 과활성화시켜 제어되지 않는 세포 성장 및 분열을 일으켜 난소암 발병에 기여할 수 있습니다. 난소암에서 일반적으로 돌연변이되는 발암유전자의 예로는 KRAS, BRAF 및 PIK3CA가 있습니다.

후성적 변경: 후성적 변경은 기본 DNA 서열에 대한 변경을 포함하지 않는 유전자 발현의 변경을 말합니다. 후생유전학적 변화는 난소암 발병에 관여하는 유전자 발현의 변화를 초래할 수 있습니다. 예를 들어, DNA 메틸화, 히스톤 변형 및 마이크로RNA 발현의 변화는 모두 난소암 발병에 기여할 수 있습니다.

염색체 이상: 결실, 복제 및 전좌와 같은 염색체 이상도 난소암 발병에 기여할 수 있습니다. 이러한 이상은 세포 성장 및 분열에 관여하는 주요 유전자의 손실 또는 증가로 이어져 통제되지 않은 세포 성장 및 분열로 이어질 수 있습니다.

전반적으로, 난소암과 관련된 분자 유전적 기전은 복잡하고 여러 유전자 변형을 수반합니다. 이러한 메커니즘을 이해하는 것은 새로운 치료법을 개발하고 난소암 여성의 결과를 개선하는 데 중요합니다.

23/03/2023

#난소암기전

난소암의 발암기전은?

난소암은 몇 가지 가능한 발암 기전을 가진 복잡한 질병이며 난소암의 정확한 원인은 완전히 이해되지 않았습니다. 그러나 가족력, 연령, 호르몬 요인 및 환경 요인과 같이 난소암 발병 가능성을 높일 수 있는 몇 가지 알려진 위험 요인이 있습니다.

난소암 발병에 기여할 수 있는 몇 가지 가능한 메커니즘은 다음과 같습니다.

유전적 돌연변이: BRCA1 및 BRCA2와 같은 특정 유전자의 유전적 돌연변이는 난소암 발병 위험을 증가시킬 수 있습니다. 이 유전자는 일반적으로 비정상 세포의 성장을 억제하는 데 도움이 되지만 돌연변이는 이 과정을 방해할 수 있습니다.

호르몬 요인: 호르몬 불균형 또는 에스트로겐이나 프로게스테론과 같은 특정 호르몬에 대한 노출은 난소암 발병에 기여할 수 있습니다.

염증: 만성 염증은 DNA를 손상시키고 비정상적인 세포의 성장을 촉진하여 난소암의 위험을 증가시킬 수 있습니다.

환경 요인: 석면이나 활석 가루와 같은 특정 환경 독소나 화학 물질에 노출되면 난소암 발병 위험이 높아질 수 있습니다.

생활습관 요인: 흡연, 열악한 식습관, 신체 활동 부족과 같은 건강하지 못한 생활습관은 난소암 발병에 기여할 수 있습니다.

난소암의 발병은 단일 원인이 아니라 이러한 요인과 다른 요인의 조합의 결과일 가능성이 높다는 점에 유의하는 것이 중요합니다.

ChatGPT 3월 14일 버전. 무료 연구 미리보기. 우리의 목표는 AI 시스템이 보다 자연스럽고 안전하게 상호 작용하도록 만드는 것입니다. 귀하의 의견은 개선하는 데 도움이 됩니다.

11/12/2022

https://synapse.koreamed.org/upload/synapsedata/pdfdata/0192lmo/lmo-6-12.pdf