scholarly journals Disrupting Ovarian Cancer Metastatic Colonization: Insights from Metastasis Suppressor Studies

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Shaheena Khan ◽  
Jennifer L. Taylor ◽  
Carrie W. Rinker-Schaeffer
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Local Treatment ◽  
Disease Recurrence ◽  
The United States ◽  
Metastasis Suppressor ◽  
Metastatic Colonization ◽  
Cancer Metastases ◽  
Progressive Growth ◽  
Microscopic Residual Disease

Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies of metastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omental microenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases.

Tumor Residual After Surgical Cytoreduction in Prediction of Clinical Outcome in Stage IV Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

2008 ◽  
Vol 26 (1) ◽  
pp. 83-89 ◽  
Author(s):  
William E. Winter ◽  
G. Larry Maxwell ◽  
Chunqiao Tian ◽  
Michael J. Sundborg ◽  
G. Scott Rose ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Residual Disease ◽  
Gynecologic Oncology ◽  
Stage Iv ◽  
Gynecologic Oncology Group ◽  
Gynecology And Obstetrics ◽  
Microscopic Residual Disease

Purpose To identify factors predictive of poor prognosis in a similarly treated population of women with stage IV epithelial ovarian cancer (EOC). Patients and Methods A retrospective review of 360 patients with International Federation of Gynecology and Obstetrics stage IV EOC who underwent primary surgery followed by six cycles of intravenous platinum/paclitaxel was performed. A proportional hazards model was used to assess the association of potential prognostic factors with progression-free survival (PFS) and overall survival (OS). Results The median PFS and OS for this group of stage IV ovarian cancer patients was 12 and 29 months, respectively. Multivariate regression analysis revealed that histology, malignant pleural effusion, intraparenchymal liver metastasis, and residual tumor size were significant prognostic variables. Whereas patients with microscopic residual disease had the best outcome, patients with 0.1 to 1.0 cm residual disease and patients with 1.1 to 5.0 cm residual disease had similar PFS and OS. Patients with a residual size more than 5 cm had a diminished PFS and OS when compared with all other groups. Median OS for microscopic, 0.1 to 5.0 cm, and more than 5.0 cm residual disease was 64, 30, and 19 months, respectively. Conclusion Patients with more than 5 cm residual disease have the shortest PFS and OS, whereas patients with 0.1 to 1.0 and 1.1 to 5.0 cm have similar outcome. These findings suggest that ultraradical cytoreductive procedures might be targeted for selected patients in whom microscopic residual disease is achievable. Patients with less than 5.0 cm of disease initially and significant disease and/or comorbidities precluding microscopic cytoreduction may be considered for alternative therapeutic options other than primary cytoreduction.

Adoptive Cell Immunotherapy for Epithelial Ovarian Cancer

2018 ◽  
Author(s):  
Samir A. Farghaly
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Residual Disease ◽  
Adoptive Cell Therapy ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Residual Tumor ◽  
Disease Recurrence ◽  
Platinum Based Chemotherapy

The standard management for epithelial ovarian cancer (EOC) is a combination of aggressive debulking surgery with residual tumor of less than 1 cm and platinum-based chemotherapy. However, a high percentage of patients experience disease recurrence. Extensive efforts to find new therapeutic options have been made, albeit cancer cells develop drug resistance and malignant progression occurs. Novel therapeutic strategies are needed to enhance progression-free survival and overall survival of patients with advanced EOC. Several preclinical and clinical studies investigated feasibility and efficacy of adoptive cell therapy (ACT) in EOC. The aim of this chapter is to present an overview of ACT in EOC, focusing on Human Leukocyte Antigen (HLA)-restricted tumor infiltrating lymphocytes and MHC-independent immune effectors such as natural killer and cytokine-induced killer. The available data suggest that ACT may provide the best outcome in patients with low tumor burden, minimal residual disease, or maintenance therapy. Further preclinical studies and clinical trials are needed.

scholarly journals Dual Actions of Ketorolac in Metastatic Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1049 ◽  
Author(s):  
Hudson ◽  
Cook ◽  
Grimes ◽  
Muller ◽  
Adams ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Inflammatory Responses ◽  
Residual Disease ◽  
Disease Recurrence ◽  
Racemic Mixture ◽  
Clinical Issue ◽  
Anti Cancer ◽  
Simultaneous Inhibition ◽  
Inflammatory Drugs

Cytoreductive surgery and chemotherapy are cornerstones of ovarian cancer treatment, yet disease recurrence remains a significant clinical issue. Surgery can release cancer cells into the circulation, suppress anti-tumor immunity, and induce inflammatory responses that support the growth of residual disease. Intervention within the peri-operative window is an under-explored opportunity to mitigate these consequences of surgery and influence the course of metastatic disease to improve patient outcomes. One drug associated with improved survival in cancer patients is ketorolac. Ketorolac is a chiral molecule administered as a 1:1 racemic mixture of the S- and R-enantiomers. The S-enantiomer is considered the active component for its FDA indication in pain management with selective activity against cyclooxygenase (COX) enzymes. The R-enantiomer has a previously unrecognized activity as an inhibitor of Rac1 (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell division control protein 42) GTPases. Therefore, ketorolac differs from other non-steroidal anti-inflammatory drugs (NSAIDs) by functioning as two distinct pharmacologic entities due to the independent actions of each enantiomer. In this review, we summarize evidence supporting the benefits of ketorolac administration for ovarian cancer patients. We also discuss how simultaneous inhibition of these two distinct classes of targets, COX enzymes and Rac1/Cdc42, by S-ketorolac and R-ketorolac respectively, could each contribute to anti-cancer activity.

scholarly journals Photoimmunotherapy of Ovarian Cancer: A Unique Niche in the Management of Advanced Disease

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1887 ◽  
Author(s):  
Shubhankar Nath ◽  
Mohammad Ahsan Saad ◽  
Michael Pigula ◽  
Joseph W.R. Swain ◽  
Tayyaba Hasan
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Gynecological Cancer ◽  
Survival Rates ◽  
Stage Iv ◽  
Standard Of Care ◽  
The United States ◽  
Resistance Mechanisms ◽  
Therapeutic Outcomes ◽  
Disseminated Disease

Ovarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths in the United States, with five-year survival rates of 15–20% for stage III cancers and 5% for stage IV cancers. The standard of care for advanced OvCa involves surgical debulking of disseminated disease in the peritoneum followed by chemotherapy. Despite advances in treatment efficacy, the prognosis for advanced stage OvCa patients remains poor and the emergence of chemoresistant disease localized to the peritoneum is the primary cause of death. Therefore, a complementary modality that is agnostic to typical chemo- and radio-resistance mechanisms is urgently needed. Photodynamic therapy (PDT), a photochemistry-based process, is an ideal complement to standard treatments for residual disease. The confinement of the disease in the peritoneal cavity makes it amenable for regionally localized treatment with PDT. PDT involves photochemical generation of cytotoxic reactive molecular species (RMS) by non-toxic photosensitizers (PSs) following exposure to non-harmful visible light, leading to localized cell death. However, due to the complex topology of sensitive organs in the peritoneum, diffuse intra-abdominal PDT induces dose-limiting toxicities due to non-selective accumulation of PSs in both healthy and diseased tissue. In an effort to achieve selective damage to tumorous nodules, targeted PS formulations have shown promise to make PDT a feasible treatment modality in this setting. This targeted strategy involves chemical conjugation of PSs to antibodies, referred to as photoimmunoconjugates (PICs), to target OvCa specific molecular markers leading to enhanced therapeutic outcomes while reducing off-target toxicity. In light of promising results of pilot clinical studies and recent preclinical advances, this review provides the rationale and methodologies for PIC-based PDT, or photo-immunotherapy (PIT), in the context of OvCa management.

Rational Use of Cytotoxic Chemotherapy for Recurrent Ovarian Cancer

2006 ◽  
Vol 4 (9) ◽  
pp. 947-953 ◽  
Author(s):  
Joyce Liu ◽  
Ursula Matulonis
Keyword(s):  
Ovarian Cancer ◽  
Treatment Options ◽  
Recurrent Ovarian Cancer ◽  
Disease Recurrence ◽  
The United States ◽  
Phase Iii ◽  
Optimal Timing ◽  
Duration Of Treatment ◽  
Phase Iii Trials

Ovarian cancer remains the leading cause of death among women with gynecologic malignancies, and the fifth leading cause of cancer mortality in women in the United States. Although many patients respond to first-line platinum-based therapy, most will experience disease recurrence. The role of further therapy in the setting of recurrent ovarian cancer is palliative, and large randomized phase III trials on treatment options for recurrent ovarian cancer are rare. Controversies exist as to the optimal timing and duration of treatment, and many issues regarding treatment of recurrent disease remain.

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