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

Cancer Stem Cells as the Key to Cancer: Special Emphasis on Prostate Cancer Ghayeel Abo Kassm α , Gaelle Antar σ , Maya Atwi ρ , Tony Butrus Ѡ , Elias Hajjar ¥ , Osamah Jaafar § , Marita Machrekeki χ , Eddy Mikhael ν , Jessica Swesa Ѳ , Fadi Mikhael ζ & Muriel T. Zaatar £ Abstract- Recent research into cancer stem cells has refined our knowledge of the origins, maintenance, and progression of cancer. The characteristics of tumor initiating cells and the stem-like properties of tumor side populations that appear to be responsible for tumor maintenance and metastasis have given insights into potential targets for the elimination of treatment-resistant and residual tumor cells. These insights have also provided inroads to understanding and preventing invasive and metastatic progression of cancer. In this review, we discuss recent advancements in understanding of tumor initiating cells and cancer stem cells and their implications on cancer pathobiology and treatment. The role of tumor initiating cell phenotypes on routes of metastasis and the use of stemness markers to guide prognosis and treatment are also discussed. Particular emphasis sections are included that focus on the role of stemness in the pathobiology and treatment of prostate cancer. Of particular interest is the correlation of stemness with decreased androgen receptor expression and resistance to anti-androgen therapy. The overview provided herein represents a primer for the understanding of current knowledge regarding cancer stem cells and their clinical implications in prostate and other cancer types. I. I ntroduction espite the significant advancements in cancer therapy throughout the years, cancer remains the most common cause of death worldwide [1]. Knowledge of how cancer initiates and the cellular and molecular origins of cancer continue to grow and be refined. Cancers have been thought to be monoclonal, meaning that each primary tumor originated from a single mutated cell. Mutation in one of a variety of genes may cause cells to form a tumor, while three to seven mutations and/or chromosomal defects may be needed for the development of cancer[2]. Accumulation of mutations can occur over time leading to cancer[2]. Complicating the monoclonal view of cancer, cancer growth and development are impacted by tumor heterogeneity and cell fusion. Recent research has shown that tumor cells and lymphocytes can merge, resulting in phenotypic and genotypic variation in tumor cells [3]. Author α σ ρ Ѡ ¥ § χ ν Ѳ : Department of Biological and Physical Sciences, American University in Dubai, Dubai, United Arab Emirates. Author ζ : Oncology Department, Mediclinic City Hospital, Dubai, United Arab Emirates. Corresponding Author £ : Department of Biological and Physical Sciences, American University in Dubai, Dubai, United Arab Emirates. e-mail: mzaatar@aud.edu A population of self-renewing cells with a high tumorigenic potential has been identified in many cancers, which are known as cancer stem cells (CSCs). The continuous and uncontrolled development of malignant tumors is thought to be caused by CSCs, which are also known as cancer-initiating cells (CICs)[2]. These cells are also thought to have a crucial role in metastasis and recurrence[2]. Many theories have suggested that the events occurring in either stem or differentiated cells, such as genomic instability, an inflammatory environment, genetic recombination, and lateral genetic transformation should be taken into consideration as potential CSC origins [2]. The ability of cancer cells to proliferate and, in many circumstances, survive is dependent on underlying stemness[4]. Moreover, due to cancer stem cells' capacity to trigger tumor growth, self-renewal, and multi-drug resistance, the majority of recent cancer research has focused on determining their distinctive characteristics and origins. CSCs have been identified in a variety of tumor types, including head and neck, stomach, breast, pancreatic, lung, liver, colon, melanoma, and bladder cancers[1]. Epithelial-to-mesenchymal transition (EMT) is a strictly controlled process that is essential for the development of tumors. EMT increases cancer cells' ability to migrate and invade and has a direct impact on the production of stem cell-like tumor-initiating cells. TGF- β 1 plays crucial roles in the development of tumors and is a critical transcription factor regulating EMT [9]. Undoubtedly, all cells require energy for survival, proliferation, and cell growth. CSCs have a distinct metabolic flexibility in comparison to normal stem cells and significantly rely on oxidative phosphorylation (OXPHOS) as their main source of energy in contrast to non-CSCs, which are primarily glycolytic[5]. In the presence of oxygen, CSCs can alternate between OXPHOS and glycolysis to maintain homeostasis and consequently support tumor development [10]. The inner cell mass of the preimplantation blastocyst is a source of Embryonic Stem Cells (ESCs), which are distinguished and characterized by their pluripotency (the capacity and ability to differentiate into all derivatives of the three basic germ layers: ectoderm, endoderm, and mesoderm) and their potential to self- replicate without limit[6]. Apart from this, understanding originating cell types of cancer is a crucial step in determining mechanisms of tumor initiation and D 17 Year 2023 Global Journal of Medical Research Volume XXIII Issue II Version I ( D ) F © 2023 Global Journals