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: It is demonstrated that equilibrium occurs, is mechanistically distinguishable from elimination and escape, and that neoplastic cells in equilibrium are transformed but proliferate poorly in vivo, and it is shown that tumour cells inilibrium are unedited but become edited when they spontaneously escape immune control and grow into clinically apparent tumours.
Abstract: The capacity of immunity to control and shape cancer, that is, cancer immunoediting, is the result of three processes that function either independently or in sequence: elimination (cancer immunosurveillance, in which immunity functions as an extrinsic tumour suppressor in naive hosts); equilibrium (expansion of transformed cells is held in check by immunity); and escape (tumour cell variants with dampened immunogenicity or the capacity to attenuate immune responses grow into clinically apparent cancers). Extensive experimental support now exists for the elimination and escape processes because immunodeficient mice develop more carcinogen-induced and spontaneous cancers than wild-type mice, and tumour cells from immunodeficient mice are more immunogenic than those from immunocompetent mice. In contrast, the equilibrium process was inferred largely from clinical observations, including reports of transplantation of undetected (occult) cancer from organ donor into immunosuppressed recipients. Herein we use a mouse model of primary chemical carcinogenesis and demonstrate that equilibrium occurs, is mechanistically distinguishable from elimination and escape, and that neoplastic cells in equilibrium are transformed but proliferate poorly in vivo. We also show that tumour cells in equilibrium are unedited but become edited when they spontaneously escape immune control and grow into clinically apparent tumours. These results reveal that, in addition to destroying tumour cells and sculpting tumour immunogenicity, the immune system of a naive mouse can also restrain cancer growth for extended time periods.
1,283 citations
TL;DR: It is provided evidence that these miRNAs are potential novel oncogenes participating in the development of human testicular germ cell tumors by numbing the p53 pathway, thus allowing tumorigenic growth in the presence of wild-type p53.
1,279 citations
TL;DR: It is found that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2–M checkpoint, and phylogenetic trees across metastases show organ-specific branches.
Abstract: Christine Iacobuzio-Donahue and colleagues use whole-genome exome sequencing to analyse primary pancreatic cancers and one or more metastases from the same patients, and find that tumours are composed of distinct subclones. The authors also determine the evolutionary maps by which metastatic cancer clones have evolved within the primary tumour, and estimate the timescales of tumour progression. On the basis of these data, they estimate a mean period of 11.8 years between the initiation of pancreatic tumorigenesis and the formation of the parental, non-metastatic tumour, and a further 6.8 years for the index metastasis clone to arise. These data point to a potentially large window of opportunity during which it might be possible to detect the cancer in a relatively early form. Peter Campbell and colleagues use next-generation sequencing to detect chromosomal rearrangements in 13 patients with pancreatic cancer. The results reveal considerable inter-patient heterogeneity and indicate ongoing genomic instability and evolution during the development of metastases. But for most of the patients studied, more than half of the genetic rearrangements found were present in all metastases and the primary tumour, making them potential targets for therapeutic intervention at early and late stages of the disease. Pancreatic cancer is highly aggressive, usually because of widespread metastasis. Here, next-generation DNA sequencing has been used to detect genomic rearrangements in 13 patients with pancreatic cancer and to explore clonal relationships among metastases. The results reveal not only considerable inter-patient heterogeneity, but also ongoing genomic instability and evolution during the development of metastases. Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97–98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations1,2,3,4,5, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours6,7, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites7, and how the tumour disseminates. Here we harness advances in DNA sequencing8,9,10,11,12 to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2–M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.
1,271 citations
TL;DR: This Review focuses on the main chemokines that are found in the human tumour microenvironment, and elaborate on their patterns of expression, their regulation and their roles in immune cell recruitment and in cancer and stromal cell biology.
Abstract: The tumour microenvironment is the primary location in which tumour cells and the host immune system interact. Different immune cell subsets are recruited into the tumour microenvironment via interactions between chemokines and chemokine receptors, and these populations have distinct effects on tumour progression and therapeutic outcomes. In this Review, we focus on the main chemokines that are found in the human tumour microenvironment; we elaborate on their patterns of expression, their regulation and their roles in immune cell recruitment and in cancer and stromal cell biology, and we consider how they affect cancer immunity and tumorigenesis. We also discuss the potential of targeting chemokine networks, in combination with other immunotherapies, for the treatment of cancer.
1,271 citations
TL;DR: It is shown that normal dermal fibroblasts can be "educated" by carcinoma cells to express proinflammatory genes, and this ability to "educate" them is shown to be related to tumor-enhancing inflammation.
1,270 citations