Contents



Preface

Ovarian cancer (OC) is a heterogeneous disease composed of multiple distinct molecular and clinical subtypes. Women with OC, in particular high-grade serous ovarian cancer (HGSOC), face a formidable challenge as fatal resistance to therapies commonly occurs within a few years of diagnosis, with the exception of rare subtypes such as ovarian germ cell tumour. Improvement in our ability to target the underlying drivers and vulnerabilities of OC, together with advances in surgical techniques, are

essential to developing effective treatments for women battling this disease.

disease.

women with more advanced OC.

HGSOC accounts for much of the lethality of epithelial OC and is the OC subtype of focus in this book. However, the book also covers the genetics and mutational landscape of a rare and lesser-known ovarian cancer, granulosa cell tumour. In general, the molecular characterisation of HGSOC has revealed several subtypes associated with distinct phenotypes and clinical outcomes. The first section of this book explores the utility of OC molecular subtyping for directing therapeutic decisions, the implications of ovarian cancer genetic profiling for the patient, the current understanding of OC tumorigenesis and the role of epigenetic events in this

Most OC is diagnosed at an advanced stage and, in particular for HGSOC, often regarded as a systemic disease. Despite this, the role of surgical cytoreduction remains paramount in the management of OC diagnosed at any stage. Although there has been a significant shift in the management paradigm for women with more advanced OC from primary cytoreductive surgery (PCS) to neoadjuvant chemotherapy (NACT) followed by interval surgery, maximum cytoreduction of tumour to microscopic residual disease, also known as R0 resection or complete resection (CR), is one of the most important positive prognostic factors for women with OC. R0 resection is the current gold standard for optimal debulking surgery. The second section of the book focuses on the role of ultra-radical surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of

Unfortunately, it is inevitable that most OC will recur. More than 70% of women with HGSOC will relapse within three years, and almost all patients with the recurrent disease will eventually succumb to their cancer. The focus of any treatment is therefore mainly palliative. Chemotherapy with platinum-based or non-platinum-based agents has remained the mainstay of treatment for affected women, despite minimal gains in OC overall survival for the last three decades. It is only recently, with the introduction of poly adenosine diphosphate(ADP)-ribose polymerase inhibitors (PARPi) for treatment of patients with homologous recombination deficient (HRD) tumours, that improvements in OC overall survival is observed. To develop more effective treatments for HGSOC, an in-depth understanding of the early genetic events in HGSOC tumorigenesis is crucial. The last section of the book highlights several potential novel OC therapeutic approaches including targeting the leader cell population to increase chemotherapy sensitivity, use of nanoparticle and gas plasma technologies, and exploration of anti-parasitic drug and epigenetic therapies.
