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

mesenchyme-derived tumors metastasize by hematogenous spread[17]. CSCs exhibit high plasticity, meaning that they can change their phenotype and their appearance. These changes can be caused by chemotherapy, radiotherapeutics, senescence, and resulting changes in the tumor microenvironment (TME) [17]. Senescence can have anti-tumor effects but can also have negative effects, such as the promotion of cancer stemness, which can in turn increase plasticity, leading to tumor relapse or metastasis [17], [18]. Recent studies have indicated the importance and urgency of diagnostic screening of the TME prior to and during treatment since therapeutic efficacy and adverse effects of anti-cancer drugs can be affected by the TME [19]. In recent years, studies have provided more evidence that cancer stem cells play a pivotal role in the regulation of the TME and immunotherapeutic response in HCC patients. Recent construction of an HCC stemness subtype classifier may offer insights into the interaction between CSCs and the TME and may also be an approach for selecting immunotherapeutic responders in the future[20]. The JAK/STAT3 signaling pathway has a significant role in different types of cancers. Its activation increases metastatic and tumorigenic capability and chemoresistance in cancer by enhancing epithelial- mesenchymal transition EMT, which is related to stemness[21]. EMT is a critical regulator of cancer progression, regulating cancer spread, invasion, and survival[21]. Once activated,STAT3 enters the nucleus through importin- β 1 and allows expression of genes that promote pathways that are critical for cancer survival[21]. V. C ancer S tem C ells and P rostate C ancer S urvival VI. S tem C ell M arkers Over the years, biomarkers have been gaining attention, especially because they are used in diagnosis, therapy, and prognosis, mostly in cancer patients. Cancer stems cells have been known to drive tumor initiation and relapse[25]. Cancer stem cells originate from either differentiated cells or adult tissue resident stem cells. Their importance in disease and development has led to investigation and discovery of stem cell biomarkers. In order to identify CSCs and distinguish them from non-CSC cancer cells, a variety of markers have been used. Common markers are CD133, CD44, IL-6R, and ALDH[26], [27]. These markers, which are predominantly expressed on stem- like cells, correlate with apoptosis resistance and tumor cell growth as they are prevalent on CSCs with enhanced cellular survival phenotypes[28]. Genomic stemness-regulating regions have been investigated for use as a marker for stemness, such as the ERG + 85 enhancer region for leukemia stem cells [29].The use of a reporter to sort an ERG + 85 High fraction of acute myelogenous leukemia cells showed the ability of this population to reconstitute the original tumor heterogeneity and was used to identify a 4-Hydroxyphenyl retinamide as an inhibitor of leukemia stem cells. This demonstrates the use of CSC markers to drive drug targeting[29]. VII. E ffects of CSCS on A nti-cancer T herapy a) Correlation of Stemness with Therapy Resistance CSCs are more resistant to traditional therapies than other tumor cells and can adapt quickly to changes in the microenvironment. Radiotherapy, chemotherapy, or the cessation of treatment can trigger CSC resistance[30]. Tumorcell stemness has been associated with immune checkpoint inhibitor (ICI) resistance. A recent study used RNA sequencing to identify a pan-cancer signature corresponding to the stem.sig stemness-associated gene list that was predictive of ICI immunotherapy response[31]. Using CRISPR datasets, a list of genes involved in stemness whose knockout resulted in enhanced tumor immune response was generated. This evidence indicated that cancer stemness is associated with immunotherapy resistance and provided a genetic stemness profile that may potentially predict immunotherapy response[32]. VIII. M echanisms of D rug R esistance in C ancer S tem C ells The mechanisms that protect CSCs from chemotherapy or radiotherapy are an area of ongoing investigation. Recently, emphasis has centered on the role of the DNA damage response (DDR) in the development of tumors. It has been reported that cancer metastasis may be facilitated by an enhanced DDR that shields CSC and chemoresistant cells from the genotoxic pressure of chemotherapeutic medicines or radiation[33]. 19 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 A comprehensive study by Tsudenomi et al (2019) concluded that there is no obvious link between CSCs and a patient’s ability to survive; however, it is an integral part of establishing a prognosis [22]. Conversely, another study by Yi et al. (2020) effectively proved that prognosis and CSCs have a more direct correlation than previously discussed[23]. Specifically, an experiment was conducted by Li et al. (2020) that showed “that B7-H4 is a potential PCa [prostate cancer] stemness-associated biomarker to predict the prognosis of PCa.”[24] This means that the B7-H4 gene is a stem cell-related gene, the overexpression of which can cause tumors to grow, thus establishing a link between CSCs and poor prognosis.