Topic
Carcinogenesis
About: Carcinogenesis is a research topic. Over the lifetime, 60368 publications have been published within this topic receiving 3192599 citations. The topic is also known as: oncogenesis & tumorigenesis.
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TL;DR: The rationale for targeting TGF-β signaling in cancer is reviewed, the clinical status of pharmacological inhibitors are summarized, and the direct effects of TGF -β signaling blockade on tumor and stromal cells are discussed.
Abstract: The transforming growth factor (TGF)-β signaling pathway is deregulated in many diseases, including cancer. In healthy cells and early-stage cancer cells, this pathway has tumor-suppressor functions, including cell-cycle arrest and apoptosis. However, its activation in late-stage cancer can promote tumorigenesis, including metastasis and chemoresistance. The dual function and pleiotropic nature of TGF-β signaling make it a challenging target and imply the need for careful therapeutic dosing of TGF-β drugs and patient selection. We review here the rationale for targeting TGF-β signaling in cancer and summarize the clinical status of pharmacological inhibitors. We discuss the direct effects of TGF-β signaling blockade on tumor and stromal cells, as well as biomarkers that can predict the efficacy of TGF-β inhibitors in cancer patients.
671 citations
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TL;DR: The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53, and alterations were associated with better prognosis in a stage-independent manner.
Abstract: Gastric cancer is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Beyond mutations in TP53, alterations in other genes or pathways account for only small subsets of the disease. We performed exome sequencing of 22 gastric cancer samples and identified previously unreported mutated genes and pathway alterations; in particular, we found genes involved in chromatin modification to be commonly mutated. A downstream validation study confirmed frequent inactivating mutations or protein deficiency of ARID1A, which encodes a member of the SWI-SNF chromatin remodeling family, in 83% of gastric cancers with microsatellite instability (MSI), 73% of those with Epstein-Barr virus (EBV) infection and 11% of those that were not infected with EBV and microsatellite stable (MSS). The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53. Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results reveal the genomic landscape, and highlight the importance of chromatin remodeling, in the molecular taxonomy of gastric cancer.
670 citations
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TL;DR: This review focuses on the current understanding of the tumor promoting and the tumor suppressive functions of ROS, and highlights the potential mechanism(s) involved, and sheds light on a very novel and an actively growing field of ROS‐dependent cell death mechanism referred to as ferroptosis.
666 citations
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TL;DR: This work suggests a framework for cancer epigenetics involving three types of genes: 'epigenetic mediators', corresponding to the tumour progenitor genes suggested earlier; 'Epigenetic modifiers' of the mediators, which are frequently mutated in cancer; and 'epigetic modulators' upstream of the modifiers, which is responsive to changes in the cellular environment and often linked to the nuclear architecture.
Abstract: This year is the tenth anniversary of the publication in this journal of a model suggesting the existence of 'tumour progenitor genes'. These genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, and thus cause altered differentiation throughout tumour evolution. The past decade of discovery in cancer epigenetics has revealed a number of similarities between cancer genes and stem cell reprogramming genes, widespread mutations in epigenetic regulators, and the part played by chromatin structure in cellular plasticity in both development and cancer. In the light of these discoveries, we suggest here a framework for cancer epigenetics involving three types of genes: 'epigenetic mediators', corresponding to the tumour progenitor genes suggested earlier; 'epigenetic modifiers' of the mediators, which are frequently mutated in cancer; and 'epigenetic modulators' upstream of the modifiers, which are responsive to changes in the cellular environment and often linked to the nuclear architecture. We suggest that this classification is helpful in framing new diagnostic and therapeutic approaches to cancer.
666 citations
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TL;DR: In experiments designed to assess the role of the HER2 gene in oncogenesis, overexpression of unaltered HER2 coding sequences in NIH 3T3 cells resulted in cellular transformation and tumorigenesis.
Abstract: The HER2 gene encodes a cell-surface glycoprotein with extensive homology to the epidermal growth factor receptor. Recently it was found to be amplified in about 30% of primary human breast malignancies. In experiments designed to assess the role of the HER2 gene in oncogenesis, we found that overexpression of unaltered HER2 coding sequences in NIH 3T3 cells resulted in cellular transformation and tumorigenesis.
665 citations