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Nature Medicine Nov 2013Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the... (Review)
Review
Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
Topics: Cell Cycle Checkpoints; Disease Progression; Humans; Immunotherapy; Inflammation; Macrophages; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Stromal Cells; Tumor Microenvironment
PubMed: 24202395
DOI: 10.1038/nm.3394 -
Current Opinion in Gastroenterology Nov 2019The purpose of this review is to review the past year's literature to provide comprehensive information to researchers, physicians, and the general public regarding the... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to review the past year's literature to provide comprehensive information to researchers, physicians, and the general public regarding the epidemiology, diagnosis, and treatment of gastrointestinal stromal tumors (GISTs). Common ground as well as divergent viewpoints will be highlighted and discussed.
RECENT FINDINGS
The diagnosis of GISTs may involve imaging tests such as computed tomorgraphy scan and MRI, endoscopy with or without endoscopic ultrasound, and biopsy. Only biopsy, however, can yield a positive diagnosis. As most GISTs express KIT protein, immunostaining for KIT and/or molecular genetic testing for mutations in KIT can diagnose 95% of GISTs. Regorafenib, a drug that inhibits various protein genes that lead to GIST development is a relatively new treatment modality.
SUMMARY
The current review should enable clinicians to best select the diagnostic and treatment approaches to GIST.
Topics: Biopsy, Needle; Combined Modality Therapy; Disease-Free Survival; Early Detection of Cancer; Female; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Immunohistochemistry; Male; Neoplasm Invasiveness; Neoplasm Staging; Phenylurea Compounds; Pyridines; Risk Assessment; Survival Analysis
PubMed: 31577561
DOI: 10.1097/MOG.0000000000000584 -
Cell Oct 2011Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to... (Review)
Review
Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting.
Topics: Animals; Basement Membrane; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Prognosis; Signal Transduction; Stromal Cells
PubMed: 22000009
DOI: 10.1016/j.cell.2011.09.024 -
Annals of Surgical Oncology Oct 2020Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Complete resection is the only potentially curative... (Review)
Review
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Complete resection is the only potentially curative treatment, although recurrence is common, occurring in approximately 40-50% of patients. The introduction of effective molecularly targeted therapies for GISTs has dramatically changed the clinical management paradigms for, and prognosis of, patients with intermediate- and high-risk GISTs, as well as those with locally advanced and metastatic disease. In this article, we review landmark studies that evaluated the use and efficacy of the tyrosine kinase inhibitors imatinib and sunitinib in the adjuvant and neoadjuvant settings for resectable primary and limited resectable metastatic GISTs.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Molecular Targeted Therapy; Neoadjuvant Therapy; Neoplasm Recurrence, Local
PubMed: 32734368
DOI: 10.1245/s10434-020-08869-w -
Nature Reviews. Cancer Aug 2016Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are... (Review)
Review
Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context-dependent influence on cancer.
Topics: Cell Differentiation; Cell Lineage; Cytokines; Disease Progression; Drug Resistance, Neoplasm; Epigenesis, Genetic; Extracellular Matrix; Fibroblasts; Fibrosis; Forecasting; Humans; Mesenchymal Stem Cells; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Neovascularization, Pathologic; Stromal Cells; Tumor Microenvironment; Wound Healing
PubMed: 27550820
DOI: 10.1038/nrc.2016.73 -
Cancer Cell Mar 2012Mutationally corrupted cancer (stem) cells are the driving force of tumor development and progression. Yet, these transformed cells cannot do it alone. Assemblages of... (Review)
Review
Mutationally corrupted cancer (stem) cells are the driving force of tumor development and progression. Yet, these transformed cells cannot do it alone. Assemblages of ostensibly normal tissue and bone marrow-derived (stromal) cells are recruited to constitute tumorigenic microenvironments. Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types. Their contributory functions to hallmark capabilities are increasingly well understood, as are the reciprocal communications with neoplastic cancer cells that mediate their recruitment, activation, programming, and persistence. This enhanced understanding presents interesting new targets for anticancer therapy.
Topics: Cell Movement; Cell Proliferation; Humans; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neoplastic Stem Cells; Signal Transduction; Stromal Cells; Tumor Microenvironment
PubMed: 22439926
DOI: 10.1016/j.ccr.2012.02.022 -
Trends in Cancer Jul 2022The view of cancer as a tumor cell-centric disease is now replaced by our understanding of the interconnection and dependency of tumor stroma. Cancer-associated... (Review)
Review
The view of cancer as a tumor cell-centric disease is now replaced by our understanding of the interconnection and dependency of tumor stroma. Cancer-associated fibroblasts (CAFs), the most abundant stromal cells in the tumor microenvironment (TME), are involved in anticancer therapeutic resistance. As we unearth more solid evidence on the link between CAFs and tumor progression, we gain insight into the role of CAFs in establishing resistance to cancer therapies. Herein, we review the origin, heterogeneity, and function of CAFs, with a focus on how CAF subsets can be used as biomarkers and can contribute to therapeutic resistance in cancer. We also depict current breakthroughs in targeting CAFs to overcome anticancer therapeutic resistance and discuss emerging CAF-targeting modalities.
Topics: Cancer-Associated Fibroblasts; Drug Resistance, Neoplasm; Humans; Neoplasms; Stromal Cells; Tumor Microenvironment
PubMed: 35331673
DOI: 10.1016/j.trecan.2022.03.001 -
Digestive and Liver Disease : Official... May 2021
Topics: Aged; Antineoplastic Agents; Female; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Stomach Neoplasms
PubMed: 32682751
DOI: 10.1016/j.dld.2020.06.035 -
Cirugia Espanola 2021
Topics: Humans; Liver Neoplasms; Neoplasms, Glandular and Epithelial; Soft Tissue Neoplasms
PubMed: 34244122
DOI: 10.1016/j.cireng.2021.06.008 -
Advances in Experimental Medicine and... 2018The tumor microenvironment comprises a mass of heterogeneous cell types, including immune cells, endothelial cells, and fibroblasts, alongside cancer cells. It is... (Review)
Review
The tumor microenvironment comprises a mass of heterogeneous cell types, including immune cells, endothelial cells, and fibroblasts, alongside cancer cells. It is increasingly becoming clear that the development of this support niche is critical to the continued uncontrolled growth of the cancer. The tumor microenvironment contributes to the maintenance of cancer stemness and also directly promotes angiogenesis, invasion, metastasis, and chronic inflammation. In this chapter, we describe on the role of fibroblasts, specifically termed cancer-associated fibroblasts (CAFs), in the promotion and maintenance of cancers. CAFs have a multitude of effects on the growth and maintenance of cancer, and here we focus on their roles in modulating immune cells and responses; CAFs both inhibit immune cell access to the tumor microenvironment and inhibit their functions within the tumor. Finally, we describe the potential modulation of CAF function as an adjunct to bolster the effectiveness of cancer immunotherapies.
Topics: Animals; Drug Resistance, Neoplasm; Humans; Neoplasms; Neovascularization, Pathologic; Stromal Cells; Tumor Microenvironment
PubMed: 30155624
DOI: 10.1007/978-3-319-78127-3_6