Novel Ovarian Cancer Therapeutics

**139**

**Chapter 9**

Option

**Abstract**

Collective migration

**1. Introduction**

*and Maree Bilandzic*

Targeting Leader Cells in Ovarian

Cancer as an Effective Therapeutic

*Nazanin Karimnia, Gwo-Yaw Ho, Andrew N. Stephens* 

Majority of ovarian cancers are diagnosed at advanced stages with intra-peritoneal spread as the most common mode of disease metastasis. The formation of cancer spheroids is essential for the collective migration process, where shed tumour cells from the primary tumour form aggregates rather than disseminating as individual cells and seed within the peritoneal cavity. These cancer spheroids consist of leader cells (LC) and follower cells (FC), with the LC subset as key drivers of cellular movement and invasion. LCs have stem cell-like properties and are highly chemo-resistant with a specific survival addiction to several cell signalling pathways, such as the PI3K/AKT/mTOR pathway. We explore in this book chapter, the evidence supporting the role of LC in OC metastasis and the suppression of LC as an attractive therapeutic option for the treatment of advanced OC.

**Keywords:** Ovarian cancer, Leader Cells, KRT14, PI3K/AKT/mTOR,

**1.1 The majority of ovarian cancers disseminate passively within the** 

The majority of ovarian cancers (OC), up to 70%, are diagnosed at advanced stages (stage III-IV) with intra-peritoneal spread as the most common mode of metastasis [1]. OC dissemination is often accompanied by the formation of ascitic fluid within the peritoneal cavity [2–4]. Under normal conditions, a small amount of fluid is secreted by the peritoneal capillaries into the cavity to lubricate the movement of abdominal organs which is normally re-absorbed by the lymphatic channels as a result of intrathoracic pressure [5]. However, in the presence of malignant cells, fluid can accumulate in large volumes in the peritoneum and facilitate passive cancer cell dissemination [6]. Whilst haematogenous spread may account for some ovarian tumour metastasis [7], it is largely the passive peritoneal dissemination of

Prior to detachment from the primary tumour, OC cells are believed to exhibit a unique gene expression profile. This includes co-expression of both epithelial and mesenchymal markers and the acquisition of an epithelial-mesenchymal transition

**intraperitoneal space via ascitic fluid**

spheroids that results in ovarian cancer spread [8].
