Global Journal of Medical Research, F: Diseases, Volume 23 Issue 2

maintenance. Long-term studies have related the development of prostate glands to stem cells. Prostate cancer is the second most prevalent cause of cancer- related death for men in the developed world , which is the most commonly diagnosed malignancy in males[7]. Regression of the prostate occurs following androgen deprivation, but regeneration occurs after testosterone replacement[8]. The cells responsible for this are located in the proximal ducts and basal layer of the prostate. Numerous characteristics of prostate cancer indicate a stem cell origin[8]. Surgery, radiation, hormonal ablation, and chemotherapy are examples of traditional anti-pancreas cancer treatments. For individuals with severe and/or metastatic cancer, these treatments are ineffective despite increased attempts. Nevertheless, cancer treatments frequently fail because of residual tumor cells that survive therapy, which causes the reappearance of the disease [7]. It has been suggested that CSCs represent this residual population. The general findings reported in the literature illustrate the connection between stem cells and prostate cancer, its therapies, the latest research on cancer stem cells, and potential future technologies to overcome it, which are discussed herein. II. S tem C ells in T umor I nitiation, T umor C ell S ustainability and P rogression As stated in Afify and Seno (2019), “Cancer stem cells (CSCs), also known as cancer-initiating cells (CIC), are responsible for the sustained and uncontrolled growth of malignant tumors and are proposed to play significant roles in metastasis and recurrence.”[2] The authors clearly state that the initiation of cancer arises from stem cells. Furthermore, this statement is backed by research that was conducted by Mei et al. (2019), who presented very convincing evidence that CSCs have a substantial role in initiation of cancer[9]. This evidence shows that while there is a good understanding of how cancer cells form, the ability to prevent this from occurring remains elusive[10]. A plethora of research has been conducted that strongly supports the role that prostate cancer stem cells (PCSCs) play in the initiation of prostate cancer [9]. This drives the hypothesis that prostate stem cells are targets for prostate cancer initiation. Furthermore, it was proven by Eder et al. (2016) that cancer-associated fibroblasts (CAFs) and prostate cancer cells interact, which allows prostate cancer to proliferate and spread throughout the body [11]. Additional research by Begum et al. (2019) further supports this view [12]. They found that cancer-associated fibroblasts promoted CSC frequency, self-renewal, and metastasis in models of pancreatic ductal adenocarcinoma. III. I nverse C orrelation of A ndrogen R eceptor E xpression with S temness in P rostate C ancer Cancer progression is defined by continuous loss of a specific phenotype and the growth of progenitor and stem cell features[13]. In prostate cancer, androgen receptor (AR) signaling is important for the development of cancer and therapy resistance. AR signaling is decreased at the transcriptional level in high-grade versus low-grade prostate cancer. Resistance to androgen receptor therapy may be accompanied by loss of androgen receptor signaling and gain of stemness since loss of AR expression is associated with the development of stem cell-like features[13]. One way to inhibit AR signaling is by using the AR antagonist enzalutamide, which is one of the main treatments used for men with castration-resistant prostate cancer[14]. Furthermore, MDM2, an E3 ligase, allows for the ubiquitination of AR in CSCs, decreasing total AR protein levels[15]. The loss of MDM2 allows for the accumulation of AR leading to differentiation into luminal cells and cell death[15]. Blocking MDM2- mediated activity in concert with AR-targeted therapy can provide an approach for eliminating AR-negative CSCs in addition to AR-positive prostate cancer cells, which in turn decreases metastatic tumor burden and inhibits therapeutic resistance [15]. A study on the effects of AR demonstrated the influence of AR on the expression of CD44 and SOX2[16]. The experiment consisted of expressing AR in PC3 cells that are AR- negative. The expression levels of CD44 and SOX2 were decreased, indicating that AR-signaling can reduce stemness characteristics of these cells. IV. R ole of S tem C ells in T umor P rogression Numerous studies have introduced discrete identities of cells that have stem cell-like features and experience shifts to adapt to a changing microenvironment as the disease progresses. A tumor’s cell-of-origin determines its characteristics, such as metastasis, drug resistance, heterogeneity, and immortality[17]. A tumor that originated from cancer stem cells arising late in the life of tumors will have limited metastatic ability, a homogenous phenotype, and a restricted chemokine-receptor profile[17]. Conversely, buildup of mutations in early stem cells can produce tumors with increased rates of metastasis that are driven by a heterogeneous collection of chemokine receptors[17]. The aggressive nature of tumors is dependent on the processes of tissue formation and differentiation that are applied in the early embryonic stages. For example, ectoderm and endoderm-derived tumors metastasize through thelymphatics, while 18 Year 2023 Global Journal of Medical Research Volume XXIII Issue II Version I ( D ) F © 2023 Global Journals Cancer Stem Cells as the Key to Cancer: Special Emphasis on Prostate Cancer