Abstract
Ovarian cancer is the most lethal gynecologic malignancy, and patient prognosis has not improved significantly over the last several decades. In order to improve therapeutic approaches and patient outcomes, there is a critical need for focused research towards better understanding of the disease. Recent findings have revealed that the tumor microenvironment plays an essential role in promoting cancer progression and metastasis. The tumor microenvironment consists of cancer cells and several different types of normal cells recruited and reprogrammed by the cancer cells to produce factors beneficial to tumor growth and spread. These normal cells present within the tumor, along with the various extracellular matrix proteins and secreted factors, constitute the tumor stroma and can compose 10–60% of the tumor volume. Cancer associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, and play a critical role in promoting many aspects of tumor function. This review will describe the various hypotheses about the origin of CAFs, their major functions in the tumor microenvironment in ovarian cancer, and will discuss the potential of targeting CAFs as a possible therapeutic approach.
Highlights
Ovarian cancer is the deadliest of all the gynecologic malignancies, and is the fifth leading cause of cancer related deaths among women in the United States
The tumor stroma consists of cellular components like the cancer associated fibroblasts (CAFs), immune cells, endothelial cells, pericytes, adipocytes, and so forth, as well as acellular components like the extra cellular matrix proteins (ECMs) [3,4,5,6,7]
Cancer associated fibroblasts (CAFs) are an important constituent of the tumor stroma, and this review will focus on providing an overview of the origin, function, and potential targeting of CAFs in ovarian cancer therapy
Summary
Ovarian cancer is the deadliest of all the gynecologic malignancies, and is the fifth leading cause of cancer related deaths among women in the United States. Cancers 2018, 10, 406 malignant cells and the genetically stable stroma, a process that will determine the degree of tumor promotion and proliferation, invasiveness, potential for spread, and even patient prognosis [9]. The tumor stroma consists of cellular components like the cancer associated fibroblasts (CAFs), immune cells, endothelial cells, pericytes, adipocytes, and so forth, as well as acellular components like the extra cellular matrix proteins (ECMs) [3,4,5,6,7] Each of these tumor microenvironmental elements has been shown to play important roles in tumor growth and progression in various cancers, including ovarian cancer. CAFs are an important constituent of the tumor stroma, and this review will focus on providing an overview of the origin, function, and potential targeting of CAFs in ovarian cancer therapy
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