Ovarian Cancer: Opportunity for Targeted Therapy (original) (raw)
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A Current Review of Targeted Therapeutics for Ovarian Cancer
Journal of Oncology, 2010
Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress has been achieved in the treatment of ovarian cancer with therapeutics focused on DNA replication or cell division. However, despite sensitivity to induction chemotherapy the majority of patients will develop recurrent disease. Conventional agents for recurrent disease offer little in terms of long-term responses. Various targeted therapeutics have been explored in the management of ovarian cancer. These include monoclonal antibodies to epidermal growth factor receptors, small molecule tyrosine kinase inhibitors, monoclonal antibodies directed at the vascular endothelial growth factor (bevacizumab), and the small tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor. Recently, several other agents have come forth as potential therapeutic agents in the management of ovarian cancer. These include monoclonal antibodies to the folate receptor, triple angiokinase inhibitors, PARP inhibitors, aurora kinase inhibitors, inhibitors of the Hedgehog pathway, folate receptor antagonists, and MTOR inhibitors.
New Hypothesis on Pathogenesis of Ovarian Cancer Lead to Future Tailored Approaches
BioMed Research International, 2013
In the last decades, management of epithelial ovarian cancer (EOC) has been based on the staging system of the International Federation of Gynecology and Obstetrics (FIGO), and different classifications have been proposed for EOC that take account of grade of differentiation, histological subtype, and clinical features. However, despite taxonomic efforts, EOC appears to be not a unique disease; its subtypes differ for epidemiological and genetic risk factors, precursor lesions, patterns of spread, response to chemotherapy, and prognosis. Nevertheless, carboplatin plus paclitaxel combination represents the only standard treatment in adjuvant and advanced settings. This paper summarizes theories about the classification and origin of EOC and classical and new prognostic factors. It presents data about standard treatment and novel agents. We speculate about the possibility to create tailored therapy based on specific mutations in ovarian cancer and to personalize prevention.
Diverse molecular pathways in ovarian cancer and their clinical significance
Maturitas, 2009
The origin of epithelial ovarian cancer remains unknown. It is believed to develop from ovarian surface epithelium, post-ovulatory inclusion cysts, endometriosis and more recently the fimbrial end of the fallopian tube. Molecular evidence suggests that ovarian cancer may progress both through a stepwise mutation process (low-grade pathway, type I), and a separate pathway with high genetic instability leading to rapid metastasis without an identifiable precursor lesion (high-grade pathway, type II). This sub-classification explains the clinical and biological heterogeneity of ovarian cancer and highlights the importance for developing novel diagnostics and therapeutics targeting two unique diseases-type I and type II ovarian carcinomas. This article summarises current knowledge of the aetiology and molecular basis of ovarian cancer and discusses recent clinical strategies for type I and type II disease.
Ovarian Cancer: Biomarkers and Targeted Therapy
Biomedicines
Ovarian cancer is one of the most common causes of death in women as survival is highly dependent on the stage of the disease. Ovarian cancer is typically diagnosed in the late stage due to the fact that in the early phases is mostly asymptomatic. Genomic instability is one of the hallmarks of ovarian cancer. While ovarian cancer is stratified into different clinical subtypes, there still exists extensive genetic and progressive diversity within each subtype. Early detection of the disorder is one of the most important steps that facilitate a favorable prognosis and a good response to medical therapy for the patients. In targeted therapies, individual patients are treated by agents targeting the changes in tumor cells that help them grow, divide and spread. Currently, in gynecological malignancies, potential therapeutic targets include tumor-intrinsic signaling pathways, angiogenesis, homologous-recombination deficiency, hormone receptors, and immunologic factors. Ovarian cancer is ...
Ovarian Cancer Overview: Molecular Biology and Its Potential Clinical Application
Ovarian Cancer - From Pathogenesis to Treatment, 2018
Over the previous two decades, there has been a shift in the ovarian cancer paradigm to consider it as a multiplicity of disease types rather than a single disease, requiring specialized medical management from molecular diagnosis through to treatment. Despite the achieved improvements in diagnosis, surgery, and systemic treatment, ovarian cancer remains the leading cause of death from gynecological tumors in western countries. The study of ovarian cancer at a molecular level could reveal potential biomarkers of disease diagnosis and progression, as well as possible therapeutic targets in areas such as angiogenesis and homologous recombination deficiencies. Although this area of research is proving invaluable concerning newer therapeutic approaches, platinum-based chemotherapy continues to be the core of the first-line treatment. Genomic screening focusing on the identification of prognostic and predictive markers is considered one of the leading areas for future ovarian cancer research.
2013
Copyright © 2012 Donavon Hiss. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The hallmarks of ovarian cancer encompass the development of resistance, disease recurrence and poor prognosis. Ovarian cancer cells express gene signatures which pose significant challenges for cancer drug development, therapeutics, prevention and management. Despite enhancements in contemporary tumor debulking surgery, tentative combination regimens and abdominal radiation which can achieve beneficial response rates, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapse. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free and overall response rates in ovarian cancer patients. Currently, a revival in cancer drug discove...
International Journal of Gynecologic Cancer, 2012
ObjectiveTo review the current understanding of the underlying molecular, biologic, and genetic mechanisms involved in ovarian cancer development and how these mechanisms can be targets for prevention, detection, and treatment of the disease and its recurrence.MethodsIn May 2012, we convened a meeting of researchers, clinicians, and consumer advocates to review the state of current knowledge on molecular mechanisms and identify fruitful areas for further investigations.ResultsThe meeting consisted of 7 scientific sessions ranging from Epidemiology, Early Detection, and Biology to Therapeutics and Quality of Life. Sessions consisted of talks and panel discussions by international leaders in ovarian cancer research. A special career development session by the Congressionally Directed Medical Research Program Department of Defense Ovarian Cancer Academy as well as an oral abstract and poster session showcased promising new research by junior scientists.ConclusionsTechnological advances...
Molecular Targeted Therapies in the Treatment of Ovarian Cancer
The outcome of treatment for patients with advanced ovarian cancer, despite recent improvements, remains poor. New therapeutic approaches are urgently required. Biologic agents in the form of monoclonal antibodies and small molecular targeting agents (e.g. tyrosine kinase inhibitors) appear promising and many of these are currently undergoing early clinical evaluation. However, these agents are mostly cytostatic and this has implications for their clinical use as well as in assessments of efficacy in pre-clinical models. These agents generally have relatively low single-agent activity and therefore may be most effective either as modulators of activity of other agents including cytotoxics and other biologic agents or as maintenance therapy. We have learnt that carefully matching the choice of therapy to patient characteristics and tumour biology is essential for this approach to be successful, reflecting the molecular heterogeneity of ovarian cancer; indeed, the search for more effective tumour predictive biomarkers is ongoing. In ovarian cancer, the role of maintenance therapy has not been established and it is in this setting that we think these agents may be particularly helpful, in addition to their possible roles as adjuvant therapies and in relapsed disease. Ultimately, the hope is not just to increase progression free survival but to improve overall survival by devising strategies to prevent and overcome resistance to treatment.
Targeted Therapies for Ovarian Cancer
Best Practice & Research Clinical Obstetrics & Gynaecology, 2017
Epithelial ovarian cancer has the highest mortality rate of all gynaecological malignancies. Most women present with advanced disease and develop a recurrence after radical surgery and chemotherapy. Improving the results of first-or subsequent line chemotherapy has been slow and novel approaches to systemic treatment are needed. Ovarian cancer is a heterogeneous disease with complex molecular and genetic changes. Understanding these better will provide information on the mechanisms of resistance and opportunities to target therapy more rationally, exploiting specific changes in the tumour. Here we review targeted approaches to therapy, focussing on targeting angiogenesis and inhibition of DNA repair, two areas that show promising activity. Additionally, we review studies that are underway targeting the cell cycle and signalling pathwayYs as well as immunotherapeutic strategies. Many of these innovative approaches already demonstrate promising activity in ovarian cancer, and have the potential to improve the outcome in women with ovarian cancer.