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Cancer Cell Jul 2018The transcription factor NRF2 is the master regulator of the cellular antioxidant response. Though recognized originally as a target of chemopreventive compounds that... (Review)
Review
The transcription factor NRF2 is the master regulator of the cellular antioxidant response. Though recognized originally as a target of chemopreventive compounds that help prevent cancer and other maladies, accumulating evidence has established the NRF2 pathway as a driver of cancer progression, metastasis, and resistance to therapy. Recent studies have identified new functions for NRF2 in the regulation of metabolism and other essential cellular functions, establishing NRF2 as a truly pleiotropic transcription factor. In this review, we explore the roles of NRF2 in the hallmarks of cancer, indicating both tumor suppressive and tumor-promoting effects.
Topics: Animals; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; NF-E2-Related Factor 2; Neoplasm Metastasis; Neoplasms; Signal Transduction
PubMed: 29731393
DOI: 10.1016/j.ccell.2018.03.022 -
Cancer Biology & Therapy 2019Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in... (Review)
Review
Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in cancer management. We will review the current understanding of the origin of circulating cell-free DNA and different forms of DNA release (including various types of cell death and active secretion processes) and clearance routes. The dynamics of extracellular DNA in blood during therapy and the role of circulating DNA in pathophysiological processes (tumor-associated inflammation, NETosis, and pre-metastatic niche development) provide insights into the mechanisms that contribute to tumor development and metastases formation. Better knowledge of circulating tumor-specific cell-free DNA could facilitate the development of new therapeutic and diagnostic options for cancer management.
Topics: Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Cell-Free Nucleic Acids; Circulating Tumor DNA; DNA, Neoplasm; Humans; Liquid Biopsy; Neoplasms; Organ Specificity
PubMed: 30990132
DOI: 10.1080/15384047.2019.1598759 -
Nature Sep 2013Phenotypic and functional heterogeneity arise among cancer cells within the same tumour as a consequence of genetic change, environmental differences and reversible... (Review)
Review
Phenotypic and functional heterogeneity arise among cancer cells within the same tumour as a consequence of genetic change, environmental differences and reversible changes in cell properties. Some cancers also contain a hierarchy in which tumorigenic cancer stem cells differentiate into non-tumorigenic progeny. However, it remains unclear what fraction of cancers follow the stem-cell model and what clinical behaviours the model explains. Studies using lineage tracing and deep sequencing could have implications for the cancer stem-cell model and may help to determine the extent to which it accounts for therapy resistance and disease progression.
Topics: Animals; Cell Differentiation; Cell Lineage; Cell Transformation, Neoplastic; Clonal Evolution; Disease Progression; Drug Resistance, Neoplasm; Genetic Heterogeneity; Humans; Neoplasms; Neoplastic Stem Cells
PubMed: 24048065
DOI: 10.1038/nature12624 -
CA: a Cancer Journal For Clinicians 2023Cancer development is driven by the accumulation of alterations affecting the structure and function of the genome. Whereas genetic changes disrupt the DNA sequence,... (Review)
Review
Cancer development is driven by the accumulation of alterations affecting the structure and function of the genome. Whereas genetic changes disrupt the DNA sequence, epigenetic alterations contribute to the acquisition of hallmark tumor capabilities by regulating gene expression programs that promote tumorigenesis. Shifts in DNA methylation and histone mark patterns, the two main epigenetic modifications, orchestrate tumor progression and metastasis. These cancer-specific events have been exploited as useful tools for diagnosis, monitoring, and treatment choice to aid clinical decision making. Moreover, the reversibility of epigenetic modifications, in contrast to the irreversibility of genetic changes, has made the epigenetic machinery an attractive target for drug development. This review summarizes the most advanced applications of epigenetic biomarkers and epigenetic drugs in the clinical setting, highlighting commercially available DNA methylation-based assays and epigenetic drugs already approved by the US Food and Drug Administration.
Topics: Humans; Epigenesis, Genetic; Neoplasms; DNA Methylation; Cell Transformation, Neoplastic
PubMed: 36512337
DOI: 10.3322/caac.21765 -
Molecular Cancer Jan 2022Cellular metabolism constitutes a fundamental process in biology. During tumor initiation and progression, each cellular component in the cancerous niche undergoes... (Review)
Review
Cellular metabolism constitutes a fundamental process in biology. During tumor initiation and progression, each cellular component in the cancerous niche undergoes dramatic metabolic reprogramming, adapting to a challenging microenvironment of hypoxia, nutrient deprivation, and other stresses. While the metabolic hallmarks of cancer have been extensively studied, the metabolic states of the immune cells are less well elucidated. Here we review the metabolic disturbance and fitness of the immune system in the tumor microenvironment (TME), focusing on the impact of oncometabolites to the function of immune cells and the clinical significance of targeting metabolism in anti-tumor immunotherapy. Metabolic alterations in the immune system of TME offer novel therapeutic insight into cancer treatment.
Topics: Adaptation, Biological; Animals; Cell Transformation, Neoplastic; Cellular Reprogramming; Combined Modality Therapy; Disease Management; Disease Susceptibility; Energy Metabolism; Humans; Immune System; Immunomodulation; Immunotherapy; Neoplasms; Treatment Outcome; Tumor Microenvironment
PubMed: 35062950
DOI: 10.1186/s12943-021-01486-5 -
Nature Reviews. Cancer Oct 2011RAS proteins are essential components of signalling pathways that emanate from cell surface receptors. Oncogenic activation of these proteins owing to missense mutations... (Review)
Review
RAS proteins are essential components of signalling pathways that emanate from cell surface receptors. Oncogenic activation of these proteins owing to missense mutations is frequently detected in several types of cancer. A wealth of biochemical and genetic studies indicates that RAS proteins control a complex molecular circuitry that consists of a wide array of interconnecting pathways. In this Review, we describe how RAS oncogenes exploit their extensive signalling reach to affect multiple cellular processes that drive tumorigenesis.
Topics: Animals; Apoptosis; Cell Proliferation; Cell Transformation, Neoplastic; Genes, ras; Humans; Mutation, Missense; Neoplasm Metastasis
PubMed: 21993244
DOI: 10.1038/nrc3106 -
The FEBS Journal Nov 2022Autophagy is a catabolic process that captures cellular waste and degrades them in the lysosome. The main functions of autophagy are quality control of cytosolic... (Review)
Review
Autophagy is a catabolic process that captures cellular waste and degrades them in the lysosome. The main functions of autophagy are quality control of cytosolic proteins and organelles, and intracellular recycling of nutrients in order to maintain cellular homeostasis. Autophagy is upregulated in many cancers to promote cell survival, proliferation, and metastasis. Both cell-autonomous autophagy (also known as tumor autophagy) and non-cell-autonomous autophagy (also known as host autophagy) support tumorigenesis through different mechanisms, including inhibition of p53 activation, sustaining redox homeostasis, maintenance of essential amino acids levels in order to support energy production and biosynthesis, and inhibition of antitumor immune responses. Therefore, autophagy may serve as a tumor-specific vulnerability and targeting autophagy could be a novel strategy in cancer treatment.
Topics: Humans; Autophagy; Carcinogenesis; Cell Transformation, Neoplastic; Neoplasms; Lysosomes
PubMed: 34270851
DOI: 10.1111/febs.16125 -
Nature Reviews. Cancer Apr 2024Cancer has long been viewed as a genetic disease of cumulative mutations. This notion is fuelled by studies showing that ageing tissues are often riddled with clones of... (Review)
Review
Cancer has long been viewed as a genetic disease of cumulative mutations. This notion is fuelled by studies showing that ageing tissues are often riddled with clones of complex oncogenic backgrounds coexisting in seeming harmony with their normal tissue counterparts. Equally puzzling, however, is how cancer cells harbouring high mutational burden contribute to normal, tumour-free mice when allowed to develop within the confines of healthy embryos. Conversely, recent evidence suggests that adult tissue cells expressing only one or a few oncogenes can, in some contexts, generate tumours exhibiting many of the features of a malignant, invasive cancer. These disparate observations are difficult to reconcile without invoking environmental cues triggering epigenetic changes that can either dampen or drive malignant transformation. In this Review, we focus on how certain oncogenes can launch a two-way dialogue of miscommunication between a stem cell and its environment that can rewire downstream events non-genetically and skew the morphogenetic course of the tissue. We review the cells and molecules of and the physical forces acting in the resulting tumour microenvironments that can profoundly affect the behaviours of transformed cells. Finally, we discuss possible explanations for the remarkable diversity in the relative importance of mutational burden versus tumour microenvironment and its clinical relevance.
Topics: Humans; Mice; Animals; Tumor Microenvironment; Neoplasms; Oncogenes; Mutation; Cell Transformation, Neoplastic
PubMed: 38347101
DOI: 10.1038/s41568-023-00660-9 -
Journal of Virology Nov 2017Epstein-Barr virus latent membrane protein 1 (LMP1) is expressed in multiple human malignancies, including nasopharyngeal carcinoma and Hodgkin and... (Review)
Review
Epstein-Barr virus latent membrane protein 1 (LMP1) is expressed in multiple human malignancies, including nasopharyngeal carcinoma and Hodgkin and immunosuppression-associated lymphomas. LMP1 mimics CD40 signaling to activate multiple growth and survival pathways, in particular, NF-κB. LMP1 has critical roles in Epstein-Barr virus (EBV)-driven B-cell transformation, and its expression causes fatal lymphoproliferative disease in immunosuppressed mice. Here, we review recent developments in studies of LMP1 signaling, LMP1-induced host dependency factors, mouse models of LMP1 lymphomagenesis, and anti-LMP1 immunotherapy approaches.
Topics: Animals; Cell Transformation, Neoplastic; Humans; Neoplasms; Viral Matrix Proteins
PubMed: 28835489
DOI: 10.1128/JVI.01718-16 -
Current Opinion in Hematology Jul 2018In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a... (Review)
Review
PURPOSE OF REVIEW
In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment.
RECENT FINDINGS
Lymphoma supportive niche integrates a dynamic and orchestrated network of immune and stromal cell subsets producing, with a high level of spatial and kinetic heterogeneity, extracellular and membrane factors regulating tumor migration, survival, proliferation, immune escape, as well as tumor microarchitecture, and mechanical constraints. Some recent insights have improved our understanding of these various components of lymphoma microenvironment, taking into account the mechanisms underlying the coevolution of malignant and nonmalignant cells within the tumor niche.
SUMMARY
Deciphering tumor niche characteristics, functions, and origin could offer new therapeutic opportunities through the targeting of pivotal cellular and molecular components of the supportive microenvironment, favoring immune cell reactivation and infiltration, and/or limiting tumor retention within this protective niche.
Topics: Animals; Cell Transformation, Neoplastic; Drug Resistance, Neoplasm; Humans; Lymphoma, B-Cell; Stromal Cells; Tumor Microenvironment
PubMed: 29746265
DOI: 10.1097/MOH.0000000000000440