-
The New England Journal of Medicine Feb 2023
Topics: Humans; Carcinogenesis; Cell Transformation, Neoplastic; Mitochondrial Proteins; Neoplasm Metastasis
PubMed: 36791168
DOI: 10.1056/NEJMcibr2213497 -
Science (New York, N.Y.) Apr 2016Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Hypoxia is a potent... (Review)
Review
Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Hypoxia is a potent microenvironmental factor promoting metastatic progression. Clinically, hypoxia and the expression of the hypoxia-inducible transcription factors HIF-1 and HIF-2 are associated with increased distant metastasis and poor survival in a variety of tumor types. Moreover, HIF signaling in malignant cells influences multiple steps within the metastatic cascade. Here we review research focused on elucidating the mechanisms by which the hypoxic tumor microenvironment promotes metastatic progression. These studies have identified potential biomarkers and therapeutic targets regulated by hypoxia that could be incorporated into strategies aimed at preventing and treating metastatic disease.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor; Cell Hypoxia; Cell Movement; Disease Progression; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasm Invasiveness; Neoplasm Metastasis; Radiation Tolerance; Signal Transduction; Tumor Microenvironment
PubMed: 27124451
DOI: 10.1126/science.aaf4405 -
Cancer Research Feb 2021Deregulation of the mRNA translational process has been observed during tumorigenesis. However, recent findings have shown that deregulation of translation also... (Review)
Review
Deregulation of the mRNA translational process has been observed during tumorigenesis. However, recent findings have shown that deregulation of translation also contributes specifically to cancer cell spread. During metastasis, cancer cells undergo changes in cellular state, permitting the acquisition of features necessary for cell survival, dissemination, and outgrowth. In addition, metastatic cells respond to external cues, allowing for their persistence under significant cellular and microenvironmental stresses. Recent work has revealed the importance of mRNA translation to these dynamic changes, including regulation of cell states through epithelial-to-mesenchymal transition and tumor dormancy and as a response to external stresses such as hypoxia and immune surveillance. In this review, we focus on examples of altered translation underlying these phenotypic changes and responses to external cues and explore how they contribute to metastatic progression. We also highlight the therapeutic opportunities presented by aberrant mRNA translation, suggesting novel ways to target metastatic tumor cells.
Topics: Carcinogenesis; Cell Movement; Cell Survival; Epithelial-Mesenchymal Transition; Humans; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Neovascularization, Pathologic; Phenotype; Protein Biosynthesis; TOR Serine-Threonine Kinases; Transforming Growth Factor beta; Tumor Escape; Tumor Hypoxia; Tumor Microenvironment
PubMed: 33479028
DOI: 10.1158/0008-5472.CAN-20-2720 -
British Journal of Cancer Jan 2021Metastasis-directed therapy (MDT)-local therapy that is intended to eradicate specific metastatic lesions-has hitherto been used with varying degrees of clinical... (Review)
Review
Metastasis-directed therapy (MDT)-local therapy that is intended to eradicate specific metastatic lesions-has hitherto been used with varying degrees of clinical efficacy and acceptance as a meaningful therapy for metastatic disease. Over the past 25 years, however, the momentum for using MDT to manage patients with metastatic solid tumours has increased, driven by several factors. Among these factors is the recognition that patients with limited metastatic burden could potentially derive survival benefits from MDT. Furthermore, although current systemic therapies are increasingly effective, they are infrequently curative. In addition, technological advances have broadened the spectrum of metastatic lesions that can be treated with ablative intent. Here we aim to briefly review the status of evidence for the clinical benefit of MDT based on current data mainly from trials in patients with oligometastatic disease, discuss the myriad of clinical states that might fall under and beyond the definition of oligometastasis, review technological advances in MDT and their applications beyond oligometastasis, and discuss the need for the continued co-evolution of MDT and systemic therapy as we seek to understand which patients with metastatic cancer can achieve durable remission and how to optimally manage those who cannot.
Topics: Antineoplastic Agents; Humans; Neoplasm Metastasis; Neoplasms
PubMed: 33204024
DOI: 10.1038/s41416-020-01128-5 -
British Journal of Cancer Jan 2021Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract... (Review)
Review
Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, that keep anti-tumour T cells active. However, not every patient with metastatic disease benefits from this class of drugs and patients often develop resistance to these therapies over time. Tremendous research effort is now underway to uncover new immunotherapeutic targets that can be used in patients who are refractory to anti-CTLA-4 or anti-PD-1 treatment. Here, we discuss results from experimental model systems demonstrating that modulating the immune response can negatively affect metastasis formation. We focus on molecules that boost anti-tumour immune cells and opportunities to block immunosuppression, as well as cell-based therapies with enhanced tumour recognition properties for solid tumours. We also present a list of challenges in treating metastatic disease with immunotherapy that must be considered in order to move laboratory observations into clinical practice and maximise patient benefit.
Topics: Animals; Humans; Immunotherapy; Neoplasm Metastasis; Neoplasms
PubMed: 33262520
DOI: 10.1038/s41416-020-01160-5 -
Frontiers in Immunology 2019Metastatic relapse is observed in cancer patients with no clinical evidence of disease for months to decades after initial diagnosis and treatment. Disseminated cancer... (Review)
Review
Metastatic relapse is observed in cancer patients with no clinical evidence of disease for months to decades after initial diagnosis and treatment. Disseminated cancer cells that are capable of entering reversible cell cycle arrest are believed to be responsible for these late metastatic relapses. Dynamic interactions between the latent disseminated tumor cells and their surrounding microenvironment aid cancer cell survival and facilitate escape from immune surveillance. Here, we highlight findings from preclinical models that provide a conceptual framework to define and target the latent metastatic phase of tumor progression. The hope is by identifying patients harboring latent metastatic cells and providing therapeutic options to eliminate metastatic seeds prior to their emergence will result in long lasting cures.
Topics: Endoplasmic Reticulum Stress; Extracellular Matrix; Humans; Leukocytes; Neoplasm Metastasis; Neoplasm, Residual; Neoplastic Cells, Circulating; Recurrence; Tumor Microenvironment
PubMed: 31447846
DOI: 10.3389/fimmu.2019.01836 -
The Journal of Clinical Investigation Mar 2021The tumor microenvironment profoundly influences the behavior of recruited leukocytes and tissue-resident immune cells. These immune cells, which inherently have... (Review)
Review
The tumor microenvironment profoundly influences the behavior of recruited leukocytes and tissue-resident immune cells. These immune cells, which inherently have environmentally driven plasticity necessary for their roles in tissue homeostasis, dynamically interact with tumor cells and the tumor stroma and play critical roles in determining the course of disease. Among these immune cells, neutrophils were once considered much more static within the tumor microenvironment; however, some of these earlier assumptions were the product of the notorious difficulty in manipulating neutrophils in vitro. Technological advances that allow us to study neutrophils in context are now revealing the true roles of neutrophils in the tumor microenvironment. Here we discuss recent data generated by some of these tools and how these data might be synthesized into more elegant ways of targeting these powerful and abundant effector immune cells in the clinic.
Topics: Animals; Disease Progression; Humans; Immunotherapy; Models, Immunological; Neoplasm Metastasis; Neoplasms; Neutropenia; Neutrophils; Translational Research, Biomedical; Tumor Microenvironment
PubMed: 33720040
DOI: 10.1172/JCI143759 -
Bosnian Journal of Basic Medical... Aug 2017Decades of cancer research have unraveled genetic, epigenetic and molecular pathways leading to plausible therapeutic targets; many of which hold great promise in... (Review)
Review
Decades of cancer research have unraveled genetic, epigenetic and molecular pathways leading to plausible therapeutic targets; many of which hold great promise in improving clinical outcomes. Metastatic tumors become evident early on and are one of the major causes of cancer-related fatalities worldwide. This review depicts the sequential events of cancer metastasis. Genetic and epigenetic heterogeneity influences local tumor cell invasion, intravasation, survival in circulation, extravasation and colonization to distant sites. Each sequential event is associated with heterogeneous tumor microenvironment, gain of competence, unique population of cancer stem cells (CSCs), circulatory pathway, compatible niche and immune system support. A tight regulation of metastasis-promoting mechanisms and, in parallel, evading inhibitory mechanisms contribute to the severity and site of metastasis. A comprehensive understanding of tumor cell fate as an individual entity, as well as in combination with different promoting factors and associated molecular mechanisms, is anticipated in the coming years. This will enable scientists to depict design strategies for targeted cancer therapies.
Topics: Animals; Antineoplastic Agents; Humans; Neoplasm Metastasis; Neoplastic Stem Cells
PubMed: 28278128
DOI: 10.17305/bjbms.2017.1908 -
Chinese Journal of Cancer Mar 2017Worldwide, metastasis is the leading cause of more than 90% of cancer-related deaths. Currently, no specific therapies effectively impede metastasis. Metastatic... (Review)
Review
Worldwide, metastasis is the leading cause of more than 90% of cancer-related deaths. Currently, no specific therapies effectively impede metastasis. Metastatic processes are controlled by complex regulatory networks and transcriptional hierarchy. Corepressor metastasis-associated protein 3 (MTA3) has been confirmed as a novel component of nucleosome remodeling and histone deacetylation (NuRD). Increasing evidence supports the theory that, in the recruitment of transcription factors, coregulators function as master regulators rather than passive passengers. As a master regulator, MTA3 governs the target selection for NuRD and functions as a transcriptional repressor. MTA3 dysregulation is associated with tumor progression, invasion, and metastasis in various cancers. MTA3 is also a key regulator of E-cadherin expression and epithelial-to-mesenchymal transition. Elucidating the functions of MTA3 might help to find additional therapeutic approaches for targeting components of NuRD.
Topics: Animals; Co-Repressor Proteins; Epithelial-Mesenchymal Transition; Humans; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms
PubMed: 28279208
DOI: 10.1186/s40880-017-0193-8 -
International Journal of Cancer Mar 2021The conclusion derived from the information provided in this review is that disseminating tumor cells (DTC) collaborate with the microenvironment of a future metastatic... (Review)
Review
The conclusion derived from the information provided in this review is that disseminating tumor cells (DTC) collaborate with the microenvironment of a future metastatic organ site in the establishment of organ-specific metastasis. We review the basic principles of site-specific metastasis and the contribution of the cross talk between DTC and the microenvironment of metastatic sites (metastatic microenvironment [MME]) to the establishment of the organ-specific premetastatic niche; the targeted migration of DTC to the endothelium of the future organ-specific metastasis; the transmigration of DTC to this site and the seeding and colonization of DTC in their future MME. We also discuss the role played by DTC-MME interactions on tumor dormancy and on the differential response of tumor cells residing in different MMEs to antitumor therapy. Finally, we summarize some studies dealing with the effects of the MME on a unique site-specific metastasis-brain metastasis.
Topics: Animals; Humans; Neoplasm Metastasis; Neoplastic Cells, Circulating; Tumor Microenvironment
PubMed: 32761606
DOI: 10.1002/ijc.33247