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1.
Front Oncol ; 11: 702642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354950

RESUMO

Despite the recent advances in cancer patient management and in the development of targeted therapies, systemic chemotherapy is currently used as a first-line treatment for many cancer types. After an initial partial response, patients become refractory to standard therapy fostering rapid tumor progression. Compelling evidence highlights that the resistance to chemotherapeutic regimens is a peculiarity of a subpopulation of cancer cells within tumor mass, known as cancer stem cells (CSCs). This cellular compartment is endowed with tumor-initiating and metastasis formation capabilities. CSC chemoresistance is sustained by a plethora of grow factors and cytokines released by neighboring tumor microenvironment (TME), which is mainly composed by adipocytes, cancer-associated fibroblasts (CAFs), immune and endothelial cells. TME strengthens CSC refractoriness to standard and targeted therapies by enhancing survival signaling pathways, DNA repair machinery, expression of drug efflux transporters and anti-apoptotic proteins. In the last years many efforts have been made to understand CSC-TME crosstalk and develop therapeutic strategy halting this interplay. Here, we report the combinatorial approaches, which perturb the interaction network between CSCs and the different component of TME.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32982967

RESUMO

Thyroid tumors are extremely heterogeneous varying from almost benign tumors with good prognosis as papillary or follicular tumors, to the undifferentiated ones with severe prognosis. Recently, several models of thyroid carcinogenesis have been described, mostly hypothesizing a major role of the thyroid cancer stem cell (TCSC) population in both cancer initiation and metastasis formation. However, the cellular origin of TCSC is still incompletely understood. Here, we review the principal epigenetic mechanisms relevant to TCSC origin and maintenance in both well-differentiated and anaplastic thyroid tumors. Specifically, we describe the alterations in DNA methylation, histone modifiers, and microRNAs (miRNAs) involved in TCSC survival, focusing on the potential of targeting aberrant epigenetic modifications for developing novel therapeutic approaches. Moreover, we discuss the bidirectional relationship between TCSCs and immune cells. The cells of innate and adaptive response can promote the TCSC-driven tumorigenesis, and conversely, TCSCs may favor the expansion of immune cells with protumorigenic functions. Finally, we evaluate the role of the tumor microenvironment and the complex cross-talk of chemokines, hormones, and cytokines in regulating thyroid tumor initiation, progression, and therapy refractoriness. The re-education of the stromal cells can be an effective strategy to fight thyroid cancer. Dissecting the genetic and epigenetic landscape of TCSCs and their interactions with tumor microenvironment cells is urgently needed to select more appropriate treatment and improve the outcome of patients affected by advanced differentiated and undifferentiated thyroid cancers.


Assuntos
Metástase Neoplásica/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias da Glândula Tireoide/patologia , Metilação de DNA , Histonas/genética , Histonas/metabolismo , Humanos , MicroRNAs/genética , Metástase Neoplásica/genética , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Microambiente Tumoral
3.
Cancers (Basel) ; 12(6)2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32486505

RESUMO

Although improvement in early diagnosis and treatment ameliorated life expectancy of cancer patients, metastatic disease still lacks effective therapeutic approaches. Resistance to anticancer therapies stems from the refractoriness of a subpopulation of cancer cells-termed cancer stem cells (CSCs)-which is endowed with tumor initiation and metastasis formation potential. CSCs are heterogeneous and diverge by phenotypic, functional and metabolic perspectives. Intrinsic as well as extrinsic stimuli dictated by the tumor microenvironment (TME)have critical roles in determining cell metabolic reprogramming from glycolytic toward an oxidative phenotype and vice versa, allowing cancer cells to thrive in adverse milieus. Crosstalk between cancer cells and the surrounding microenvironment occurs through the interchange of metabolites, miRNAs and exosomes that drive cancer cells metabolic adaptation. Herein, we identify the metabolic nodes of CSCs and discuss the latest advances in targeting metabolic demands of both CSCs and stromal cells with the scope of improving current therapies and preventing cancer progression.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31803140

RESUMO

The majority of embryonal tumors or childhood blastomas derive from pluripotent progenitors or fetal stem cells that acquire cancer stem cell (CSC) properties: multipotency, self-renewal ability, metastatic potential, chemoresistance, more pronounced levels of drug transporters, enhanced DNA-damage repair mechanisms, and a quiescent state. Neuroblastoma (NB) is considered a neuroendocrine tumor and is the most common extracranial neoplasm in children. NB pathogenesis has frequently been associated with epigenetic dysregulation and a failure to implement a differentiation program. The origin, characteristics, and isolation of the CSC subpopulation in NB are still incompletely understood, despite the evidence that this cell subset contributes to disease recurrence and acquired resistance to standard therapies. Here, we summarize the literature regarding the isolation and characterization of CSCs in NB over the past decades, from the early recognition of the expression of stem cell factor (SCF) or its receptor c-KIT to more recent studies identifying the ability of G-CSF and STAT3 to support stem cell-like properties in NB cells. Additionally, we review the morphological variants of NB tumors whose recent epigenetic analyses have shed light on the tumor heterogeneity so common in NB. NB-derived mesenchymal stem cells have recently been isolated from primary tumors of NB patients and associated with a pro-tumorigenic role in the tumor microenvironment, enabling immune escape by tumors, and contributing to their invasive and metastatic capabilities. In particular, we will focus on epigenetic reprogramming in the CSC subpopulation in NB and strategies to target CSCs in NB.

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