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Cellular and Phenotypic Plasticity in Cancer

Cellular and Phenotypic Plasticity in Cancer
Author: Petranel Theresa Ferrao
Publisher: Frontiers Media SA
Total Pages: 79
Release: 2015-09-17
Genre: Cancer
ISBN: 2889196623
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The process of Epithelial-Mesenchymal-Transition (EMT) is known to result in a phenotype change in cells from a proliferative state to a more invasive state. EMT has been reported to drive the metastatic spread of various cancers and has also been associated with drug resistance to cytotoxics and targeted therapeutics. Recently phenotype switching akin to EMT has been reported in non-epithelial cancers such as metastatic melanoma. This process involves changes in EMT-Transcription Factors (EMT-TFs), suggesting that phenotype-switching may be common to several tumour types. It remains unclear as to whether the presence of both Epilthelial-like and Mesenchymal-like cells are a pre-requisite for phenotype switching within a tumour, how this heterogeneity is regulated, and if alteration of cell phenotype is sufficient to mediate migratory changes, or whether drivers of cell migration result in an associated phenotype switch in cancer cells. Similarly it has yet to be clarified if cells in an altered phenotype can be refractory to drug therapy or whether mediators of drug resistance induce a concurrent phenotypic change. Little is known today about the underlying genetic, epigenetic and transient changes that accompany this phenotypic switch and about the role for the tumor micro-environment in influencing it. Hence this is currently an area of speculation and keen interest in the Oncology field with wide-ranging translational implications. In this Frontiers Research Topic, we discuss our current understanding of these concepts in various cancer types including breast cancer, colorectal cancer and metastatic melanoma. This topic covers how these processes of cellular and phenotypic plasticity are regulated and how they relate to cancer initiation, progression, dormancy, metastases and response to cytotoxics or targeted therapies.

Epithelial-Mesenchymal Plasticity in Cancer Metastasis

Epithelial-Mesenchymal Plasticity in Cancer Metastasis
Author: Mohit Kumar Jolly
Publisher: MDPI
Total Pages: 512
Release: 2020-12-29
Genre: Medical
ISBN: 3039367242
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Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.

The Heterogeneity of Cancer Metabolism

The Heterogeneity of Cancer Metabolism
Author: Anne Le
Publisher: Springer
Total Pages: 186
Release: 2018-06-26
Genre: Medical
ISBN: 331977736X
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Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Philosophy of Cancer

Philosophy of Cancer
Author: Marta Bertolaso
Publisher: Springer
Total Pages: 200
Release: 2016-08-24
Genre: Philosophy
ISBN: 9402408657
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Since the 1970s, the origin of cancer is being explored from the point of view of the Somatic Mutation Theory (SMT), focusing on genetic mutations and clonal expansion of somatic cells. As cancer research expanded in several directions, the dominant focus on cells remained steady, but the classes of genes and the kinds of extra-genetic factors that were shown to have causal relevance in the onset of cancer multiplied. The wild heterogeneity of cancer-related mutations and phenotypes, along with the increasing complication of models, led to an oscillation between the hectic search of ‘the’ few key factors that cause cancer and the discouragement in face of a seeming ‘endless complexity’. To tame this complexity, cancer research started to avail itself of the tools that were being developed by Systems Biology. At the same time, anti-reductionist voices began claiming that cancer research was stuck in a sterile research paradigm. This alternative discourse even gave birth to an alternative theory: the Tissue Organization Field Theory (TOFT). A deeper philosophical analysis shows limits and possibilities of reductionist and anti-reductionist positions and of their polarization. This book demonstrates that a radical philosophical reflection is necessary to drive cancer research out of its impasses. At the very least, this will be a reflection on the assumptions of different kinds of cancer research, on the implications of what cancer research has been discovering over 40 years and more, on a view of scientific practice that is most able to make sense of the cognitive and social conflicts that are seen in the scientific community (and in its results), and, finally, on the nature of living entities with which we entertain this fascinating epistemological dance that we call scientific research. The proposed Dynamic and Relational View of carcinogenesis is a starting point in all these directions.

Successes and Challenges of NK Immunotherapy

Successes and Challenges of NK Immunotherapy
Author: Benjamin Bonavida
Publisher: Academic Press
Total Pages: 540
Release: 2021-06-23
Genre: Science
ISBN: 0128243961
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Successes and Challenges of NK Immunotherapy: Increasing Anti-tumor Efficacy describes the unique therapeutic applications of NK cells to fight cancers and eliminate the bulk and subset of cancer stem cells responsible for metastasis, relapse and recurrences. The book provides information on the development, engineering, mechanisms of action, response to various preclinical models, and applications in various clinical trials. Sections cover the development of highly engineered cytotoxic NK cells, their mechanisms of action, preclinical and clinical applications, the development and application of CAR-NK cells, and new NK-drug conjugates, also emphasizing that activated NK cells can target and kill highly resistant cancer stem cells. Written by the leading experts on NK immunotherapy worldwide, this is a valuable resource for researchers, clinicians and members of the biomedical field who are interested in understanding novel and efficient therapies to fight cancers. Discusses the unique developmental applications of NK immunotherapy against cancers, which differs greatly from other types of immunotherapies Provides up-to-date and highly relevant information through chapters written by the leading researchers in the field Presents a significant number of schematic diagrams for easy understanding and reproducibility

The Cancer Stem Cell Niche

The Cancer Stem Cell Niche
Author: Susie Nilsson
Publisher: Academic Press
Total Pages: 246
Release: 2021-02-09
Genre: Science
ISBN: 0323853250
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The Cancer Stem Cell Niche, Volume Five in the Advances in Stem Cells and their Niches series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics, including Acute lymphoblastic leukemia and the bone marrow microenvironment, Stem cell niches in bone and their roles in cancer metastasis, The role of vasculature in cancer stem cell niches, The lung cancer stem cell niche, The prostate cancer stem cell niche: Genetic drivers and therapeutic approaches, Impact of prostate cancer stem cell niches on prostate cancer tumorigenesis and progression, The testicular cancer stem cell niche. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Advances in Stem Cells and their Niches series Includes the latest information on the Cancer Stem Cell Niche

Phenotypic Switching

Phenotypic Switching
Author: Herbert Levine
Publisher: Academic Press
Total Pages: 773
Release: 2020-06-10
Genre: Medical
ISBN: 012817997X
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Phenotypic Switching: Implications in Biology and Medicine provides a comprehensive examination of phenotypic switching across biological systems, including underlying mechanisms, evolutionary significance, and its role in biomedical science. Contributions from international leaders discuss conceptual and theoretical aspects of phenotypic plasticity, its influence over biological development, differentiation, biodiversity, and potential applications in cancer therapy, regenerative medicine and stem cell therapy, among other treatments. Chapters discuss fundamental mechanisms of phenotypic switching, including transition states, cell fate decisions, epigenetic factors, stochasticity, protein-based inheritance, specific areas of human development and disease relevance, phenotypic plasticity in melanoma, prostate cancer, breast cancer, non-genetic heterogeneity in cancer, hepatitis C, and more. This book is essential for active researchers, basic and translational scientists, clinicians, postgraduates and students in genetics, human genomics, pathology, bioinformatics, developmental biology, evolutionary biology and adaptive opportunities in yeast. Thoroughly addresses the conceptual, experimental and translational aspects that underlie phenotypic plasticity Emphasizes quantitative approaches, nonlinear dynamics, mechanistic insights and key methodologies to advance phenotypic plasticity studies Features a diverse range of chapter contributions from international leaders in the field

Phenotype Plasticity and Populations' Dynamics

Phenotype Plasticity and Populations' Dynamics
Author: Marie André-Ratsimbazafy
Publisher:
Total Pages: 0
Release: 2016
Genre:
ISBN:
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It is commonly accepted that tumors arise from cells that escape the homeostatic controls which underlie the healthy histological structure and that cell phenotype is not the result of deterministic biochemical and genetic processes, but rather the stochastic and dynamic outcome of multiple intra- and intercellular regulation networks. This PhD aims to quantitatively study the phenotypic homeostasis of the cell populations and to present an approach to the fundamental question, never heretofore studied, regarding the autonomy versus collective control of cell fate. We studied in the long run, using flow cytometry and in 2D and 3D conditions, the level of expression of CD24 and CD44 of two breast cancer cell lines (SUM149-PT and SUM159-PT). Three phenotypes were isolated (CD24-/CD44+, CD24+/CD44+, CD24-/CD44-), the latter had not previously been documented in the literature. The phenotypic behavior of CD44-low and CD44-high subpopulations has been characterized by assessing their proportion and analyzing the fluorescence map. Thereby, we observed both a periodic behavior of appearance and disappearance of pool of cells characteristics of each cell lines and a phenotypic re-diversification for each subpopulation. Only the resulting population derived from CD24-/CD44- provided the same balance as the original unsorted population. 3D re-diversification process was observed in tumorspheres from CD24-/CD44+ and CD24+/CD44+. The cells CD24-/CD44did not have that potential but nonetheless outlived anoikis. These behaviors suggest that there is an inter-cell coordination regulating the balance of phenotypic proportions. To discover the social rules regulating inter-phenotypic spatial organization, we have set up a reporter of the endogenous variations of CD24 and CD44 and developed a theoretical model of cell interactions. This work has confirmed our hypothesis that inter-cellular social rules are determining the phenotypic expression at both the uni- and multicellular scales.

The Epithelial-to-Mesenchymal Transition (EMT) in Cancer

The Epithelial-to-Mesenchymal Transition (EMT) in Cancer
Author: Joëlle Roche
Publisher: MDPI
Total Pages: 261
Release: 2018-04-09
Genre: Science
ISBN: 3038427934
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This book is a printed edition of the Special Issue "The Epithelial-to-Mesenchymal Transition (EMT) in Cancer" that was published in Cancers