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Genome Medicine Mar 2020The analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with... (Review)
Review
The analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with potential for use in liquid biopsy-based personalized cancer treatment. These goals are ambitious, yet recent studies are already allowing a sharper understanding of the strengths, challenges, and opportunities provided by liquid biopsy approaches. For instance, through single-cell-resolution genomics and transcriptomics, it is becoming increasingly clear that CTCs are heterogeneous at multiple levels and that only a fraction of them is capable of initiating metastasis. It also appears that CTCs adopt multiple ways to enhance their metastatic potential, including homotypic clustering and heterotypic interactions with immune and stromal cells. On the clinical side, both CTC enumeration and molecular analysis may provide new means to monitor cancer progression and to take individualized treatment decisions, but their use for early cancer detection appears to be challenging compared to that of other tumor derivatives such as circulating tumor DNA. In this review, we summarize current data on CTC biology and CTC-based clinical applications that are likely to impact our understanding of the metastatic process and to influence the clinical management of patients with metastatic cancer, including new prospects that may favor the implementation of precision medicine.
Topics: Animals; Biomarkers, Tumor; Humans; Liquid Biopsy; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating
PubMed: 32192534
DOI: 10.1186/s13073-020-00728-3 -
Molecular Cancer Feb 2023Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages,... (Review)
Review
Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages, proneness to postoperative metastasis or recurrence, and low sensitivity to radiotherapy and chemotherapy pose a challenge for the diagnosis and treatment of RCC. Liquid biopsy is an emerging test that measures patient biomarkers, including circulating tumor cells, cell-free DNA/cell-free tumor DNA, cell-free RNA, exosomes, and tumor-derived metabolites and proteins. Owing to its non-invasiveness, liquid biopsy enables continuous and real-time collection of patient information for diagnosis, prognostic assessment, treatment monitoring, and response evaluation. Therefore, the selection of appropriate biomarkers for liquid biopsy is crucial for identifying high-risk patients, developing personalized therapeutic plans, and practicing precision medicine. In recent years, owing to the rapid development and iteration of extraction and analysis technologies, liquid biopsy has emerged as a low cost, high efficiency, and high accuracy clinical detection method. Here, we comprehensively review liquid biopsy components and their clinical applications over the past 5 years. Additionally, we discuss its limitations and predict its future prospects.
Topics: Humans; Carcinoma, Renal Cell; Liquid Biopsy; Cell-Free Nucleic Acids; Kidney Neoplasms; Biomarkers, Tumor; Neoplastic Cells, Circulating
PubMed: 36810071
DOI: 10.1186/s12943-023-01745-7 -
Cell Nov 2006Metastasis occurs when genetically unstable cancer cells adapt to a tissue microenvironment that is distant from the primary tumor. This process involves both the... (Review)
Review
Metastasis occurs when genetically unstable cancer cells adapt to a tissue microenvironment that is distant from the primary tumor. This process involves both the selection of traits that are advantageous to cancer cells and the concomitant recruitment of traits in the tumor stroma that accommodate invasion by metastatic cells. Recent conceptual and technological advances promote our understanding of the origins and nature of cancer metastasis.
Topics: Animals; Basement Membrane; Evolution, Molecular; Humans; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating; Phenotype
PubMed: 17110329
DOI: 10.1016/j.cell.2006.11.001 -
British Journal of Cancer Sep 2021The characterisation of CTCs (circulating tumour cells) and cfDNA (circulating free DNA) by Salvianti et al. highlight critical aspects of these approaches' relative...
The characterisation of CTCs (circulating tumour cells) and cfDNA (circulating free DNA) by Salvianti et al. highlight critical aspects of these approaches' relative strengths, weaknesses, and interdependencies in this study.
Topics: Cell Count; Cell-Free Nucleic Acids; Colonic Neoplasms; GTP Phosphohydrolases; Humans; Liquid Biopsy; Membrane Proteins; Mutation; Neoplasm Metastasis; Neoplastic Cells, Circulating; Proto-Oncogene Proteins p21(ras); Survival Analysis
PubMed: 33953346
DOI: 10.1038/s41416-021-01397-8 -
Nature Communications Apr 2023Circulating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the "best" indicator of metastatic risk because their...
Circulating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the "best" indicator of metastatic risk because their heterogeneity is generally neglected. In this study, we develop a molecular typing system to predict colorectal cancer metastasis potential based on the metabolic fingerprints of single CTCs. After identification of the metabolites potentially related to metastasis using mass spectrometry-based untargeted metabolomics, setup of a home-built single-cell quantitative mass spectrometric platform for target metabolite analysis in individual CTCs and use of a machine learning method composed of non-negative matrix factorization and logistic regression, CTCs are divided into two subgroups, C1 and C2, based on a 4-metabolite fingerprint. Both in vitro and in vivo experiments demonstrate that CTC count in C2 subgroup is closely associated with metastasis incidence. This is an interesting report on the presence of a specific population of CTCs with distinct metastatic potential at the single-cell metabolite level.
Topics: Humans; Neoplastic Cells, Circulating; Biomarkers, Tumor; Epithelial-Mesenchymal Transition; Metabolomics; Neoplasm Metastasis
PubMed: 37120634
DOI: 10.1038/s41467-023-38009-3 -
Cancer Cell Nov 2011Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression toward metastasis but it is unknown whether...
Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression toward metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGFβ and direct platelet-tumor cell contacts synergistically activate the TGFβ/Smad and NF-κB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-κB signaling in cancer cells or ablation of TGFβ1 expression solely in platelets protects against lung metastasis in vivo. Thus, cancer cells rely on platelet-derived signals outside of the primary tumor for efficient metastasis.
Topics: Animals; Blood Platelets; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Lung Neoplasms; Mice; Mice, Inbred C57BL; Molecular Sequence Data; NF-kappa B; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplastic Cells, Circulating; Signal Transduction; Transforming Growth Factor beta1
PubMed: 22094253
DOI: 10.1016/j.ccr.2011.09.009 -
Cold Spring Harbor Perspectives in... Apr 2020The dynamic interplay between neoplastic cells and the immune microenvironment regulates every step of the metastatic process. Immune cells contribute to invasion by... (Review)
Review
The dynamic interplay between neoplastic cells and the immune microenvironment regulates every step of the metastatic process. Immune cells contribute to invasion by secreting a cornucopia of inflammatory factors that promote epithelial-to-mesenchymal transition and remodeling of the stroma. Cancer cells then intravasate to the circulatory system assisted by macrophages and use several pathways to avoid recognition by cytotoxtic lymphocytes and phagocytes. Circulating tumor cells that manage to adhere to the vasculature and encounter premetastic niches are able to use the associated myeloid cells to extravasate into ectopic organs and establish a dormant microscopic colony. If successful at avoiding repetitive immune attack, dormant cells can subsequently grow into overt, clinically detectable metastatic lesions, which ultimately account to most cancer-related deaths. Understanding how disseminated tumor cells evade and corrupt the immune system during the final stages of metastasis will be pivotal in developing new therapeutic modalities that combat metastasis.
Topics: Cell Adhesion; Epithelial-Mesenchymal Transition; Humans; Macrophages; Neoplasm Metastasis; Neoplastic Cells, Circulating; Tumor Microenvironment
PubMed: 31501262
DOI: 10.1101/cshperspect.a037424 -
Cold Spring Harbor Perspectives in... May 2020Metastatic disease is the leading cause of death in patients with solid cancers. The progression to metastasis is a multistep process that involves detachment of tumor... (Review)
Review
Metastatic disease is the leading cause of death in patients with solid cancers. The progression to metastasis is a multistep process that involves detachment of tumor cells from their constraining basement membrane at the primary site, migration and intravasation into the circulation, survival in the circulation, extravasation into the secondary organ, and survival and growth at the secondary site. During these steps, tumor and immune cells interact and influence each other both within the tumor microenvironment and systemically. In particular, myeloid cells such as monocytes, macrophages, neutrophils, and myeloid-derived suppressor cells (myeloid regulatory cells) have been shown to play important roles in the metastatic process. These interactions open new avenues for targeting cancer metastasis, especially given the increasing interest in development of cancer immunotherapies. In this review, we describe the currently reported pathways and mechanisms involved in myeloid cell enhancement of the metastatic cascade.
Topics: Animals; Humans; Immunotherapy; Myeloid Cells; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating; Tumor Microenvironment
PubMed: 31548218
DOI: 10.1101/cshperspect.a038026 -
Expert Review of Molecular Diagnostics Oct 2017Minimally invasive methods will augment the clinical approach for establishing the diagnosis or monitoring treatment response of central nervous system tumors. Liquid... (Review)
Review
Minimally invasive methods will augment the clinical approach for establishing the diagnosis or monitoring treatment response of central nervous system tumors. Liquid biopsy by blood or cerebrospinal fluid sampling holds promise in this regard. Areas covered: In this literature review, the authors highlight recent studies describing the analysis of circulating tumor cells, cell free nucleic acids, and extracellular vesicles as strategies to accomplish liquid biopsy in glioblastoma and metastatic tumors. The authors then discuss the continued efforts to improve signal detection, standardize the liquid biopsy handling and preparation, develop platforms for clinical application, and establish a role for liquid biopsies in personalized medicine. Expert commentary: As the technologies used to analyze these biomarkers continue to evolve, we propose that there is a future potential to precisely diagnose and monitor treatment response with liquid biopsies.
Topics: Biomarkers, Tumor; Brain Neoplasms; Circulating MicroRNA; Circulating Tumor DNA; Exosomes; Humans; Liquid Biopsy; Neoplastic Cells, Circulating
PubMed: 28875730
DOI: 10.1080/14737159.2017.1374854 -
International Journal of Molecular... Dec 2020Circulating tumor cells (CTCs) are a rare tumor cell subpopulation induced and selected by the tumor microenvironment's extreme conditions. Under hypoxia and starvation,... (Review)
Review
Circulating tumor cells (CTCs) are a rare tumor cell subpopulation induced and selected by the tumor microenvironment's extreme conditions. Under hypoxia and starvation, these aggressive and invasive cells are able to invade the lymphatic and circulatory systems. Escaping from the primary tumor, CTCs enter into the bloodstream to form metastatic deposits or re-establish themselves in cancer's primary site. Although radiotherapy is widely used to cure solid malignancies, it can promote metastasis. Radiation can disrupt the primary tumor vasculature, increasing the dissemination of CTCs. Radiation also induces epithelial-mesenchymal transition (EMT) and eliminates suppressive signaling, causing the proliferation of existent, but previously dormant, disseminated tumor cells (DTCs). In this review, we collect the results and evidence underlying the molecular mechanisms of CTCs and DTCs and the effects of radiation and hypoxia in developing these cells.
Topics: Animals; Humans; Neoplasm Invasiveness; Neoplasms; Neoplastic Cells, Circulating; Radiation Tolerance; Tumor Hypoxia
PubMed: 33339353
DOI: 10.3390/ijms21249592