A Current Review of Targeted Therapeutics for Ovarian Cancer (original) (raw)

Targeted agents in epithelial ovarian cancer: review on emerging therapies and future developments

ecancermedicalscience, 2016

Epithelial ovarian cancer (EOC) remains a clinical challenge and there is a need to optimise the currently available treatment and to urgently develop new therapeutic strategies. Recently, there has been improved understanding of the molecular characteristics and tumour microenvironment of ovarian cancers. This has facilitated the development of various targeted agents used concurrently with chemotherapy or as maintenance. Most of the studies have explored the tumour angiogenesis pathways. In phase-III trials, bevacizumab showed a statistically significant improvement in progression-free survival, although there was no improvement in overall survival in selected high-risk cases. Although several multi-targeted tyrosine kinase inhibitors were found to be useful, the toxicity and survival benefit has to be weighed. Poly ADP ribose polymerase (PARP) inhibitors have been another marvellous molecule found to be effective in breast cancer 1, early onset (BRCA)-positive ovarian cancers. Several newer molecules targeting Her 2, Wee tyrsine kinases, PIP3/AKT/mTR-signalling pathways, folate receptors are under development and may provide additional opportunities in the future. This article focuses on the targeted agents that have successfully paved the way in the management of epithelial ovarian cancer and the newer molecules that may offer therapeutic opportunities in the future.

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.

Advances in ovarian cancer therapy

Cancer Chemotherapy and Pharmacology, 2017

Epithelial ovarian cancer is typically diagnosed at an advanced stage. Current state-of-the-art surgery and chemotherapy result in the high incidence of complete remissions; however, the recurrence rate is also high. For most patients, the disease eventually becomes a continuum of symptom-free periods and recurrence episodes. Different targeted treatment approaches and biological drugs, currently under development, bring the promise of turning ovarian cancer into a manageable chronic disease. In this review, we discuss the current standard in the therapy for ovarian cancer, major recent studies on the new variants of conventional therapies, and new therapeutic approaches, recently approved and/or in clinical trials. The latter include anti-angiogenic therapies, polyADP-ribose polymerase (PARP) inhibitors, inhibitors of growth factor signaling, or folate receptor inhibitors, as well as several immunotherapeutic approaches. We also discuss cost-effectiveness of some novel therapies and the issue of better selection of patients for personalized treatment.

Current status of bevacizumab in advanced ovarian cancer

OncoTargets and Therapy, 2013

Ovarian cancer is the most lethal gynecological cancer, mainly because of the delay in diagnosis. Recently, much effort has been put into investigating and introducing novel targeted agents into clinical practice, with the aim of improving prognosis and quality of life. Angiogenesis is a possible target. The aim of this review is to investigate the most common molecular pathways of angiogenesis, which have provided novel targets for tailored therapy in patients with ovarian cancer. These therapeutic strategies include monoclonal antibodies and tyrosine-kinase inhibitors. These drugs have as molecular targets vascular endothelial growth factor, vascular endothelial growth factor receptors, platelet-derived growth factor, fibroblast growth factor, and angiopoietin. Bevacizumab was investigated in several Phase III studies, with interesting results. Today, there is strong evidence for introducing bevacizumab in the treatment of patients with advanced and recurrent ovarian cancer. Nevertheless, further investigations and large clinical trials are needed to understand the safety and effectiveness of bevacizumab, the optimal duration and timing of treatment, and activity in association with other chemotherapeutic and targeted agents. It also is necessary to identify biologic factors predictive of efficacy to choose the most appropriate antiangiogenic agent in the integrated treatment of epithelial ovarian cancer.

Ovarian Cancer: Opportunity for Targeted Therapy

Journal of Oncology, 2012

Ovarian cancer is a common cause of cancer mortality in women with limited treatment effectiveness in advanced stages. The limitation to treatment is largely the result of high rates of cancer recurrence despite chemotherapy and eventual resistance to existing chemotherapeutic agents. The objective of this paper is to review current concepts of ovarian carcinogenesis. We will review existing hypotheses of tumor origin from ovarian epithelial cells, Fallopian tube, and endometrium. We will also review the molecular pathogenesis of ovarian cancer which results in two specific pathways of carcinogenesis: (1) type I low-grade tumor and (2) type II high-grade tumor. Improved understanding of the molecular basis of ovarian carcinogenesis has opened new opportunities for targeted therapy. This paper will also review these potential therapeutic targets and will explore new agents that are currently being investigated.

New perspectives on targeted therapy in ovarian cancer

International Journal of Women's Health, 2015

Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose) inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer.

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.

Role of molecular agents and targeted therapy in clinical trials for women with ovarian cancer

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2011

There is now a greater understanding of the molecular pathways in ovarian cancer, and using this knowledge, a large number of new therapeutic agents can be tested. The success of these drugs will depend on selecting drugs that target known key dysfunctional molecular pathways. To make best use of these compounds, prognostic and predictive biomarkers need to be identified. Novel methods of assessment such as functional imaging need to be developed as additional biological end points to evaluate these therapies. Promising antitumor activity has been observed with some drugs, and careful consideration is needed to determine in what circumstances new agents, such as antiangiogenic compounds, could be considered as a standard therapy. These areas were discussed at the 4th Ovarian Cancer Consensus Conference.

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 ...