There is a critical need to develop broad-spectrum as well as individualized molecular-targeted therapies for EOC, and so current research interest is to identify signal MLN8237 datasheet transduction pathways and target key molecular role players that direct ovarian tumor sensitivity and resistance selleck chemical to therapy [44, 45]. The aim of this review is to outline recent developments in our understanding of the interrelationships among selected ovarian CSC biomarkers, heterogeneous
expression signatures and related molecular signal transduction pathways, and their translation into futuristic as well as more efficacious targeted treatment strategies. Cancer stem cell A recent American Association for Cancer Research (AACR) workshop defined CSC as a malignant cancer
cell with a stem cell phenotype . YH25448 nmr Whilst the CSC hypothesis does not specifically address the mechanisms of malignant transformation, it has been suggested that CSCs are the malignant counterparts of normal adult tissue SCs which, due to dysregulated signaling pathways, are unable to maintain stem cell homeostasis. As well as the normal Scs, also CSCs are thought to reside at the top of the lineage hierarchy and give rise to differentiated cells, which themselves have no potential for self-renewal, and therefore do not contribute significantly to tumor growth. Due to their long life, SCs remain in a tissue for longer periods compared to their differentiated progeny, thereby making them more likely to acquire transforming mutations. Additionally, it is generally accepted that SCs are more resistant to apoptosis and DNA damage and they are therefore more likely to survive to any insults [46, 47]. Whilst being quiescent in normal tissue, SCs are able to maintain their pool by undergoing
asymmetric cell division during biological processes such as the occurrence of tissue damage. During this process, a SC divides asymmetrically to generate an identical daughter cell that is committed to differentiation. It has been suggested that in this way CSCs generate the different cell types Non-specific serine/threonine protein kinase within a tumor, leading to tumor self-renew as well. Specific signaling pathways are involved in embryogenesis processes, leading to the development of various organs. We are talking about several key pathways, such as sonic Hedgehog, Notch, PTEN, BMI-1, WNT, and p53. During the development of cancer an alteration of these pathways occurs and this event could lead to dysregulation of SC self-renewal and contribute to tumor proliferation [19, 48]. The SC pool is also tightly regulated by signaling pathways from the microenvironment of the SC niche, and several of these pathways, including Hedgehog and Wnt, have been implicated in carcinogenesis [49, 50]. This may have very important implications in therapeutic interventions, including explanation for the development of chemoresistance. A role for CSCs in propagating and maintaining metastases has been proposed [51–54].