**1. Introduction**

High-grade serous ovarian carcinoma (HGSOC, ovarian cancer) is the most common and most fatal type of gynecologic malignancy. HGSOC accounts for 75% of all epithelial ovarian cancers and for 5% of all cancer deaths [1, 2]. In most cases, HGSOC develops without symptoms and is diagnosed at an advanced stage, when malignant cells are already disseminated within the peritoneal cavity [2, 3]. Metastasis in ovarian cancer commonly occurs via transcoelomic routes, which is associated with cell detachment from the primary tumor site and dissemination as single cells or spheroids, where alterations in cell-cell and cell-extracellular matrix adhesion play a critical role [3–5]. Among the transmembrane adhesion molecules that have altered expression and function in many cancers, including in ovarian cancer, are

integrins [6]. In humans, 24 different integrins are formed by specific combinations of 18 α and 8 β non-covalently bound heterodimer subunits [7, 8]. The large extracellular domains of integrins recognize specific amino acid sequences that are found on extracellular matrix (ECM) proteins such as fibronectin, collagen, laminin, and vitronectin. The short cytoplasmic tails in the c-terminus of integrins are linked to the actin cytoskeleton [7, 9]. Upon binding to ligands, integrins cluster to form adhesion complexes, which are comprised of proteins and enzymes that play roles in maintaining bidirectional signaling activities [10, 11]. In "outside-in" signaling, integrins that are bound to ECM ligands activate signaling pathways that lead to cellular responses, including survival and differentiation. Via this physical link, integrins can also transduce signals in a force-dependent manner, when the cell is exposed to mechanical stimuli. In "inside-out" signaling, intracellular conformational changes modulate the affinity of the integrins to ECM ligands [9–13]. Therefore, in addition to cell adhesion, a variety of cellular behaviors including differentiation, growth, and migration, can be mediated by integrins [7, 11]. In cancer, the expression and activation of integrins can be aberrant [14]. Additionally, since the ECM of solid tumors is usually disorganized and the crosslinking of ECM proteins is increased, integrinmediated signaling is also altered, leading to the progression and drug resistance of the disease [15, 16]. Specifically in ovarian cancer, integrins play a key role in cancer cell detachment, migration, spheroid formation, and invasion, including as a result of the movement of fluid that accumulates within the peritoneal cavity, known as ascites (**Figure 1**) [5].

### **Figure 1.**

*Integrins play a key role in ovarian cancer progression including cell detachment from primary sites, spheroid formation, migration, adhesion to secondary sites, and invasion.*

This review describes the role of integrins in ovarian cancer and discusses the current literature in integrin-targeted approaches for ovarian cancer, including photochemistry-based imaging and therapy.
