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Cell Apr 2023Most cancer-associated deaths occur due to metastasis, yet our understanding of metastasis as an evolving, heterogeneous, systemic disease and of how to effectively... (Review)
Review
Most cancer-associated deaths occur due to metastasis, yet our understanding of metastasis as an evolving, heterogeneous, systemic disease and of how to effectively treat it is still emerging. Metastasis requires the acquisition of a succession of traits to disseminate, variably enter and exit dormancy, and colonize distant organs. The success of these events is driven by clonal selection, the potential of metastatic cells to dynamically transition into distinct states, and their ability to co-opt the immune environment. Here, we review the main principles of metastasis and highlight emerging opportunities to develop more effective therapies for metastatic cancer.
Topics: Humans; Neoplasm Metastasis; Neoplasms
PubMed: 37059065
DOI: 10.1016/j.cell.2023.03.003 -
The Journal of Experimental Medicine Jan 2021Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for... (Review)
Review
Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and signaling molecules needed for proliferation, survival, invasion, metastasis, and response to the tumor microenvironment impact and cancer therapy. Here, we summarize and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in cancer cells and introduce different approaches that have been clinically used to disrupt lipid metabolism in cancer therapy.
Topics: Animals; Cell Proliferation; Humans; Immunotherapy; Lipid Metabolism; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment
PubMed: 33601415
DOI: 10.1084/jem.20201606 -
Science (New York, N.Y.) Apr 2020Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of... (Review)
Review
Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of tumor metabolism. Metabolic heterogeneity among human tumors poses a challenge to developing therapies that exploit metabolic vulnerabilities. Recent work also demonstrates that the metabolic properties and preferences of a tumor change during cancer progression. This produces distinct sets of vulnerabilities between primary tumors and metastatic cancer, even in the same patient or experimental model. We review emerging concepts about metabolic reprogramming in cancer, with particular attention on why metabolic properties evolve during cancer progression and how this information might be used to develop better therapeutic strategies.
Topics: Animals; Disease Progression; Humans; Mice; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Precancerous Conditions
PubMed: 32273439
DOI: 10.1126/science.aaw5473 -
Signal Transduction and Targeted Therapy Mar 2020Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. Yet, it remains poorly understood. The continuous evolution of... (Review)
Review
Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. Yet, it remains poorly understood. The continuous evolution of cancer biology research and the emergence of new paradigms in the study of metastasis have revealed some of the molecular underpinnings of this dissemination process. The invading tumor cell, on its way to the target site, interacts with other proteins and cells. Recognition of these interactions improved the understanding of some of the biological principles of the metastatic cell that govern its mobility and plasticity. Communication with the tumor microenvironment allows invading cancer cells to overcome stromal challenges, settle, and colonize. These characteristics of cancer cells are driven by genetic and epigenetic modifications within the tumor cell itself and its microenvironment. Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions. In this review, the authors explore the recent advancements in the field of metastasis and highlight the latest insights that contribute to shaping this hallmark of cancer.
Topics: Epigenesis, Genetic; Humans; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment
PubMed: 32296047
DOI: 10.1038/s41392-020-0134-x -
Signal Transduction and Targeted Therapy Aug 2020Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins,... (Review)
Review
Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular RNA, etc., which play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, we mainly summarized as followed: the role of exosome contents in cancer, focusing on proteins and noncoding RNA; the interaction between exosomes and tumor microenvironment; the mechanisms that epithelial-mesenchymal transition, invasion and migration of tumor affected by exosomes; and tumor suppression strategies based on exosomes. Finally, the application potential of exosomes in clinical tumor diagnosis and therapy is prospected, which providing theoretical supports for using exosomes to serve precise tumor treatment in the clinic.
Topics: Epithelial-Mesenchymal Transition; Exosomes; Humans; Neoplasm Proteins; Neoplasms; RNA, Neoplasm
PubMed: 32759948
DOI: 10.1038/s41392-020-00261-0 -
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 -
Cell Systems Aug 2019Cancer metastasis is no longer viewed as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as successfully metastasizing... (Review)
Review
Cancer metastasis is no longer viewed as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as successfully metastasizing cells assume new phenotypes while jettisoning older behaviors. The lack of a systemic understanding of this complex phenomenon has limited progress in developing treatments for metastatic disease. Because metastasis has traditionally been investigated in distinct physiological compartments, the integration of these complex and interlinked aspects remains a challenge for both systems-level experimental and computational modeling of metastasis. Here, we present some of the current perspectives on the complexity of cancer metastasis, the multiscale nature of its progression, and a systems-level view of the processes underlying the invasive spread of cancer cells. We also highlight the gaps in our current understanding of cancer metastasis as well as insights emerging from interdisciplinary systems biology approaches to understand this complex phenomenon.
Topics: Animals; Disease Progression; Humans; Neoplasm Metastasis; Neoplasms; Signal Transduction; Systems Biology
PubMed: 31465728
DOI: 10.1016/j.cels.2019.07.003 -
Annual Review of Pathology 2015Neoplastic transformation results in a wide variety of cellular alterations that impact the growth, survival, and general behavior of affected tissue. Although genetic... (Review)
Review
Neoplastic transformation results in a wide variety of cellular alterations that impact the growth, survival, and general behavior of affected tissue. Although genetic alterations underpin the development of neoplastic disease, epigenetic changes can exert an equally significant effect on neoplastic transformation. Among neoplasia-associated epigenetic alterations, changes in cellular glycosylation have recently received attention as a key component of neoplastic progression. Alterations in glycosylation appear to not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Many of these changes may support neoplastic progression, and unique alterations in tumor-associated glycosylation may also serve as a distinct feature of cancer cells and therefore provide novel diagnostic and even therapeutic targets.
Topics: Animals; Cell Transformation, Neoplastic; Epigenesis, Genetic; Glycosylation; Humans; Neoplasm Proteins; Neoplasms
PubMed: 25621663
DOI: 10.1146/annurev-pathol-012414-040438 -
Cancer Research Jun 2019Metastasis is the primary cause of cancer morbidity and mortality. The process involves a complex interplay between intrinsic tumor cell properties as well as... (Review)
Review
Metastasis is the primary cause of cancer morbidity and mortality. The process involves a complex interplay between intrinsic tumor cell properties as well as interactions between cancer cells and multiple microenvironments. The outcome is the development of a nearby or distant discontiguous secondary mass. To successfully disseminate, metastatic cells acquire properties in addition to those necessary to become neoplastic. Heterogeneity in mechanisms involved, routes of dissemination, redundancy of molecular pathways that can be utilized, and the ability to piggyback on the actions of surrounding stromal cells makes defining the hallmarks of metastasis extraordinarily challenging. Nonetheless, this review identifies four distinguishing features that are required: motility and invasion, ability to modulate the secondary site or local microenvironments, plasticity, and ability to colonize secondary tissues. By defining these first principles of metastasis, we provide the means for focusing efforts on the aspects of metastasis that will improve patient outcomes.
Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Tumor Microenvironment
PubMed: 31053634
DOI: 10.1158/0008-5472.CAN-19-0458 -
Cancer Cell Aug 2022Metastasis, the major cause of cancer death, represents one of the major challenges in oncology. Scientists are still trying to understand the biological basis...
Metastasis, the major cause of cancer death, represents one of the major challenges in oncology. Scientists are still trying to understand the biological basis underlying the dissemination and outgrowth of tumor cells, why these cells can remain dormant for years, how they become resistant to the immune system or cytotoxic effects of systemic therapy, and how they interact with their new microenvironment. We asked experts to discuss some of the unknowns, advances, and areas of opportunity related to cancer metastasis.
Topics: Humans; Immune System; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment
PubMed: 35944497
DOI: 10.1016/j.ccell.2022.07.010