Ovarian carcinoma is the leading cause of death from gynecologic malignancy in the US. Factors such as the molecular heterogeneity of ovarian tumors and frequent diagnosis at advanced stages hamper effective disease treatment. There is growing emphasis on the identification and development of targeted therapies to disrupt molecular pathways in cancer. The epidermal growth factor (EGF) receptor is one such protein target with potential utility in the management of ovarian cancer. This paper will discuss contributions of EGF receptor activation to ovarian cancer pathogenesis and the status of EGF receptor inhibitors and EGF receptor targeted therapies in ovarian cancer treatment.

Reema Zeineldin

Carolyn Y. Muller

M. Sharon Stack

Laurie G. Hudson

Targeting the EGF Receptor for Ovarian Cancer Therapy

Recurrent ovarian cancer is a lethal disease, and few patients can be cured. Although most patients receive standardized surgery and chemotherapy, the status of recurrent disease is heterogeneous. The site of recurrence and the survival intervals after recurrence are also widely distributed. Among a number of factors, many clinical trials identified time to recurrence was the factor most related to chemosensitivity at first relapse. The current recommendation for platinum sensitive ovarian cancer is a carboplatin containing combination chemotherapy. Generally, a single agent is chosen for platinum resistant ovarian cancer. Patients with single site recurrence and a long disease free interval are candidates for secondary cytoreduction, which may provide longer survival. There are several treatment choices at first relapse, and disease status, chemotherapy-free interval, and the patient&#39;s condition play a major role in the decision making process.

Kimio Ushijima

Treatment for Recurrent Ovarian Cancer&#8212;At First Relapse

Ovarian cancer is the fifth largest cancer killer in women. Improved understanding of the molecular pathways implicated in the pathogenesis of ovarian cancer has led to the investigation of novel targeted therapies. Ovarian cancer is characterized by an imbalance between pro- and antiangiogenic factors in favor of angiogenesis activation. Various antivascular strategies are currently under investigation in ovarian cancer. They can schematically be divided into antiangiogenic and vascular-disrupting therapies. This paper provides a comprehensive review of these new treatments targeting the tumor vasculature in this disease. Promising activities have been detected in phase II trials, and results of phase III clinical trials are awaited eagerly.

Francois P. Duhoux

Jean-Pascal Machiels

Antivascular Therapy for Epithelial Ovarian Cancer

Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating ovarian cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in a variety of ovarian cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the <svg     style="vertical-align:-3.27599pt;width:56.287498px;" id="M1" height="20.275" version="1.1" viewBox="0 0 56.287498 20.275" width="56.287498"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg> gene in human ovarian carcinoma cells. In xenograft models, some of HDACIs have demonstrated antitumor activity with only few side effects. Some clinical trials demonstrate that HDACI drugs provide an important class of new mechanism-based therapeutics for ovarian cancer. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating ovarian cancer, especially focusing on preclinical studies and clinical trials.

Noriyuki Takai

Hisashi Narahara

Histone Deacetylase Inhibitor Therapy in Epithelial Ovarian Cancer

Poly(ADP-ribose) polymerase-1 (PARP-1) is an important novel target in cancer therapy. This enzyme is essential in the repair of single-stranded breaks in DNA  via the base excision repair pathway. Drugs which inhibit PARP are emerging as a promising new class of anticancer agents particularly effective against tumors which have lost homologous recombination (HR) through loss of functional BRCA1 and BRCA2. PARP inhibitors potentially represent a major breakthrough for patients with hereditary BRCA-associated cancers. Furthermore their role in sporadic epithelial ovarian cancer is emerging with identification of additional subpopulations of women who may benefit a priority. This paper will summarize the mechanism of action of PARP inhibition and its role in the treatment of BRCA1-  and 2-associated cancers. We will then expand on the broader relevance and future directions for PARP inhibition in the clinical setting.

Lilian T. Gien

Helen J. Mackay

The Emerging Role of PARP Inhibitors in the Treatment of Epithelial Ovarian Cancer

The epidermal growth factor receptor is overexpressed in up to 60&#37; of ovarian epithelial malignancies. EGFR regulates complex cellular events due to the large number of ligands, dimerization partners, and diverse signaling pathways engaged. In ovarian cancer, EGFR activation is associated with increased malignant tumor phenotype and poorer patient outcome. However, unlike some other EGFR-positive solid tumors, treatment of ovarian tumors with anti-EGFR agents has induced minimal response. While the amount of information regarding EGFR-mediated signaling is considerable, current data provides little insight for the lack of efficacy of anti-EGFR agents in ovarian cancer. More comprehensive, systematic, and well-defined approaches are needed to dissect the roles that EGFR plays in the complex signaling processes in ovarian cancer as well as to identify biomarkers that can accurately predict sensitivity toward EGFR-targeted therapeutic agents. This new knowledge could facilitate the development of rational combinatorial therapies to sensitize tumor cells toward EGFR-targeted therapies.

Doris R. Siwak

Mark Carey

Bryan T. Hennessy

Catherine T. Nguyen

Mollianne J. McGahren Murray

Laura Nolden

Gordon B. Mills

Targeting the Epidermal Growth Factor Receptor in Epithelial Ovarian Cancer: Current Knowledge and Future Challenges

The aim of this study was to investigate the therapeutic efficacy of <svg style="vertical-align:-0.1254pt;width:8.9375px;" id="M2" height="7.1750002" version="1.1" viewBox="0 0 8.9375 7.1750002" width="8.9375"  xmlns="http://www.w3.org/2000/svg">
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J&#246;rgen Elgqvist

H&#229;kan Andersson

Holger Jensen

Helena Kahu

Sture Lindegren

Elisabet Warnhammar

Ragnar Hultborn

Repeated Intraperitoneal <svg style="vertical-align:-0.1638pt" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FC" d="M545 106q-67 -118 -134 -118q-24 0 -40 37.5t-30 129.5h-2q-47 -72 -103 -119.5t-108 -47.5q-47 0 -76 45.5t-29 119.5q0 113 85 204t174 91q47 0 70 -33.5t43 -119.5h3q32 47 80 140l55 13l10 -9q-47 -80 -138 -201q17 -99 27.5 -136t22.5 -37q23 0 69 61zM333 204&#xA;q-14 98 -31 149.5t-50 51.5q-49 0 -94 -70t-45 -164q0 -55 15.5 -86t40.5 -31q70 0 164 150z" /></g></svg>-Radioimmunotherapy of Ovarian Cancer in Mice

Initial surgical management is commonly accepted to date as paramount in the treatment of women presenting with epithelial ovarian cancer and permits the assessment of the disease (staging), the histological confirmation of disease type and grade, and the practice of maximal debulking preceding platinum-based chemotherapy. Many studies have shown that the volume of residual disease after initial surgical cytoreduction inversely correlates with survival. Thus, women with optimal debulking performed by a trained specialist have improved median survival. In this review, we will focus on the answers gleaned from clinical trials on primary and interval surgery, which prompts the question on the timing of surgery in respect to chemotherapy. Interval debulking surgery (IDS) is secondary cytoreduction following primary debulking and is carried out in between the courses of chemotherapy. The major clinical trials and the latest systematic reviews seem unable to give any definitive guidance or recommendation for clinical practice. The choice of aggressive primary cytoreduction or upfront chemotherapy followed by second line surgical cytoreduction seems among others to have to be individualized according to tumour load, prediction of its resectability, and response to chemotherapy. The role of tumour biology must also be kept in mind. Finally, concrete answers are awaited on the timing of surgery from the ongoing prospective randomized control trials (CHORUS and EORTC 55971) though preliminary data from the latter have already been presented at major meetings (IGCS 2008; SGO 2009) and ignited strong debate.

Igor E. Martinek

Sean Kehoe

When Should Surgical Cytoreduction in Advanced Ovarian Cancer Take Place?

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<p><em>Journal of Oncology</em> publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.</p>


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<p>Chief Editor, Professor Bruno Vincenzi, is an Associate Professor of Medical Oncology at University Campus Bio-Medico, Italy. His research interests include urogenital neoplasms and the pathophysiology and treatment of bone metastases.</p>


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Journal of Oncology

Epithelial Ovarian Cancer: Focus on Targeted Therapy