Preface

Ovarian cancer is a heterogeneous disease composed of multiple distinct molecular and clinical subtypes. Improvements in the ability to target the underlying drivers of ovarian cancer, combined with advances in surgical techniques, are crucial for developing effective treatments for patients with ovarian cancer. In this book different aspects of recent advances, new perspectives and applications in the treatment of ovarian cancer will be addressed.

Several studies have been carried out to determine the complexity of ovarian cancer as a disease with multiple distinct types that presents with symptoms similar to those in other gynecological, gastrointestinal and genitourinary diseases. Most ovarian tumors are malignant variants of common epithelial and germ cell tumors, and are classified histologically based on the presumed tissue of origin. The first chapter is focusing on "A Succinct Molecular Profile of High-Grade Ovarian Cancer". Molecular diagnosis is now aiding the early detection and treatment of ovarian cancer even before metastasis sets in. Thus, studying the molecular profiles of each type is key to understanding the origin and pathogenesis as well as genetic aberrations and mutations involved in the development of the disease. Ovarian cancers originate either from the ovary or fallopian tube, and are principally found to harbor mutations in PTEN, KRAS, BRAF, BRCA1, BRCA2 and TP53, with TP53 mutations being the most frequent. Advanced methods of detecting these genes in blood and uterine lavage can be anticipated in the very near future. There is an urgent need for further studies on the detailed mechanisms underlying the role of mutant TP53 in ovarian cancer development and its potential role in therapeutic interventions.

Ovarian tumors are a heterogeneous group of neoplasms classified based on histopathologic type and grade of differentiation. They comprise a broad range of tumors from benign and borderline to malignant histotypes characterized by different histopathological, immunophenotypic and molecular features. The chapter "Recent Advances in Classification and Histopathological Diagnosis of Ovarian Epithelial Malignant Tumours" presents an overview of recent advances in ovarian epithelial malignant tumor classification along with the histopathological, immunophenotypic and molecular diagnostic criteria, highlighting discrepancies or changes in terminology, and diagnostic challenges. These changes provide a better understanding of the nature of ovarian tumors and lead to more efficient therapeutic management of these pathological entities.

The chapter "Role of Human Epididymis Protein 4 in Tumour Angiogenesis" discusses the human epididymis protein 4 (HE4), a secretory protein expressed in the reproductive tract and respiratory epithelium in normal individuals. The HE4 serum level is raised in various solid cancers, enabling its use as a diagnostic and prognostic biomarker. It is an established biomarker of epithelial ovarian cancer (EOC) and is also significant in various other malignancies including cancer of the endometrium, cervix, lung and breast. Studies also show HE4 as an independent prognostic biomarker in non-small cell lung carcinoma. HE4 promotes angiogenesis via the STAT3 signaling pathway.

The chapter "Integrins in Ovarian Cancer: Survival Pathways, Malignant Ascites and Targeted Photochemistry" describes the role of integrins in ovarian cancer. Integrins are surface adhesion molecules that, upon binding to ligands, cluster to form adhesion complexes. These adhesion complexes are comprised of structural and regulatory proteins that modulate a variety of cellular behaviors, including differentiation, growth, and migration, through bidirectional signaling activities. Aberrant integrin expression and activation in ovarian cancer play a key role in the detachment of cancer cells from primary sites as well as migration, invasion and spheroid formation. An emerging area is the activation or rearrangement of integrins due to mechanical stress in the tumor microenvironment, particularly in response to fluid shear stress imparted by currents of malignant ascites. The chapter focuses on the effect of malignant ascites and crosstalk with survival pathways, and reviews the literature on integrin-targeting approaches in ovarian cancer, including targeted photochemistry for therapy and imaging.

Epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy in the Western world, has historically been treated with surgery followed by chemotherapy. The chapter "PARP Inhibitors in the Treatment of Epithelial Ovarian Cancer" examines the antineoplastic activity of poly (ADP-ribose) polymerase inhibitors (PARPis), one of the most active new targeted therapies for the treatment of EOC. PARPis' mechanism of action relies on their ability to interfere with DNA repair events, leading ultimately to cell death, the biological concept known as synthetic lethality. Initially developed as a maintenance therapy in patients responding to platinum-based chemotherapy in a recurrent setting, PARPis are now approved as a frontline treatment strategy. The chapter describes the clinical development studies which led to their approval, as well as safety and the management of adverse events associated with this new class of drugs. Rational considerations for the use of PARPis in the frontline setting are also discussed.

In summary, this book brings together a number of leading opinions and discoveries from experts treating ovarian cancer, highlighting the rapidly evolving understanding of the tumor biology of this devastating disease.

> **Michael Friedrich** Department of Obstetrics and Gynecology, Helios Hospital, Krefeld, Germany

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Section 1

Molcular Profile and

Classification of Ovarian

Cancer

Section 1
