Intrinsic and Extrinsic Factors Impacting Cancer Stemness and Tumor Progression

SIMPLE SUMMARY: Presently, the study of cancer stem cells is important because these cells increase the cancer complexity, confer tumors the ability to grow, resist treatment, and survive in adverse conditions. One of the properties that these cells have is stemness. Cancer stemness is modulated by the tumor microenvironment, which influences cancer stem cell function and survival. This review includes information about cancer stem cells and their regulation by extrinsic and intrinsic factors. Pluripotency factors and signaling pathways, which regulate and modulate cancer stemness are summarized in this review. In addition, it provides an overview of the models that allow the study of cancer stem cells for the development of new targeted therapies. ABSTRACT: Tumor heterogeneity represents an important limitation to the development of effective cancer therapies. The presence of cancer stem cells (CSCs) and their differentiation hierarchies contribute to cancer complexity and confer tumors the ability to grow, resist treatment, survive unfavorable conditions, and invade neighboring and distant tissues. A large body of research is currently focusing on understanding the properties of CSCs, including their cellular and molecular origin, as well as their biological behavior in different tumor types. In turn, this knowledge informs strategies for targeting these tumor initiating cells and related cancer stemness. Cancer stemness is modulated by the tumor microenvironment, which influences CSC function and survival. Several advanced in vitro models are currently being developed to study cancer stemness in order to advance new knowledge of the key molecular pathways involved in CSC self-renewal and dormancy, as well as to mimic the complexity of patients’ tumors in pre-clinical drug testing. In this review, we discuss CSCs and the modulation of cancer stemness by the tumor microenvironment, stemness factors and signaling pathways. In addition, we introduce current models that allow the study of CSCs for the development of new targeted therapies.