{"title":"Telomerase and immortalization","authors":"L. Collopy, K. Tomita","doi":"10.1093/MED/9780198779452.003.0015","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0015","url":null,"abstract":"The lifetime of a cell is set by the terminal ends of our chromosomes, ageing timers called telomeres. Most dividing cells, not exceptional for cancers, require telomeres to protect chromosomes. However, telomere erosion occurs at every cell cycle, thus imposing a proliferative capacity, eventually triggering a growth arrest. Cancer cells must overcome this proliferative limit in order to continue dividing. In the vast majority of cases, the growth and progression of cancers correlates with the upregulation of telomerase, an enzyme that replenishes telomeres. Telomerase is not active in normal, differentiated cells and its reactivation in cancer renders cells immortal and promotes their continued growth and development. Curiously, in cancer telomerase maintains short telomeres, retaining chromosome instability. Here, we briefly take you through history of cellular mortality with the connection to telomeres and telomerase and review their function in the normal cell to address their role during the transformation to malignancy.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115300428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular profiling in cancer research and personalized medicine","authors":"P. Dam, S. V. Laere","doi":"10.1093/MED/9780198779452.003.0024","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0024","url":null,"abstract":"Recent efforts by worldwide consortia such as The Cancer Genome Atlas and the International Cancer Genome Consortium have greatly accelerated our knowledge of human cancer biology. Nowadays, complete sets of human tumours that have been characterized at the genomic, epigenomic, transcriptomic, or proteomic level are available to the research community. The generation of these data was made possible thanks to the application of high-throughput molecular profiling techniques such as microarrays and next-generation sequencing. The primary conclusion from current profiling experiments is that human cancer is a complex disease characterized by extreme molecular heterogeneity, both between and within the classical, tissue-defined cancer types. This molecular variety necessitates a paradigm shift in patient management, away from generalized therapy schemes and towards more personalized treatments. This chapter provides an overview of how molecular cancer profiling can assist in facilitating this transition. First, the state-of-the-art of molecular breast cancer profiling is reviewed to provide a general background. Then, the most pertinent high-throughput molecular profiling techniques along with various data mining techniques (i.e. unsupervised clustering, statistical learning) are discussed. Finally, the challenges and perspectives with respect to molecular cancer profiling, also from the perspective of personalized medicine, are summarized.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114888017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Benign tumours: The forgotten neoplasms","authors":"F. Pezzella, A. Harris, M. Tavassoli","doi":"10.1093/MED/9780198779452.003.0031","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0031","url":null,"abstract":"Benign tumours are exceedingly common neoplastic growth which, similar to malignant tumours, recognize genetic basis. However, benign tumours differ in one essential characteristic: by definition, these neoplasms do not produce metastases. Only some types are at risk of progression into a malignant lesion. Complete surgical removal is always curative. Because of their non-aggressive ‘benign’ nature and, in many cases, easy, straightforward possibility of surgical treatment, the biology of these tumours has not received much attention as compared to that of the malignant neoplasms. However, several studies have recently started to unveil the involvement of mechanisms overlapping with those of the malignant lesions, raising the issue that, by ignoring the biology of benign tumours, we are perhaps missing information vital for understanding malignancies. Only a few types have been subjects of studies comparable to that we can found in malignancy and therefore their biology is still largely unknown.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123465791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The signalling pathways in cancer","authors":"Jiangting Hu, F. Pezzella","doi":"10.1093/MED/9780198779452.003.0012","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0012","url":null,"abstract":"The signalling pathways allow communication between the outside world and the cell: for this very reason they are also known as ‘environmental information processing’ pathways. Signalling pathways are made up by many different types of molecules which work together to control one or more cell functions in response to a given stimulus. The first part of the chapter will deal with the general principles, types of signals received by the cell, the receptors available, and how they transmit the signals to the downstream components. In the second part, we will present the basic ‘anatomy’ of these pathways and their main roles in cancer.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121511582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blood vessels and cancer","authors":"F. Pezzella, R. Kerbel","doi":"10.1093/MED/9780198779452.003.0022","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0022","url":null,"abstract":"Like any other organ of the human body, tumours need a blood supply to provide oxygen and nutrients and to eliminate wastes. Although already the ancient Greeks had realized that there is a close relationship between tumours and blood vessels, the nature and significance of such a relationship has been debated for centuries. During the last 40 years the prevalent view, based primarily on the hypothesis of the late Judah Folkman and work undertaken since, has been that a tumour can only grow progressively if it is constantly inducing production of new vessels. No cancer could become larger than a few millimetres, or no metastases could develop if some new vessels were not produced (i.e. if there was ‘angiogenesis’). This concept lead to the conclusion that drugs able to block the growth of new vessels could therefore ‘cure’ or at least ‘block’ cancer by inducing a sustained state of dormancy. While some benefits have indeed been achieved using such drugs, these have been usually modest. Perhaps more worrying, both in animal models and in human trials, occasional progression of tumours to a more malignant phenotype during antiangiogenic treatment has been sometime observed, following an initial benefit. The study of these ‘non-angiogenic’ tumours has opened a new field in cancer biology, but so far, we have only just scratched the surface.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122245970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The multicellular organism and cancer","authors":"F. Pezzella, D. Kerr, M. Tavassoli","doi":"10.1093/MED/9780198779452.003.0001","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0001","url":null,"abstract":"Cancer is a disease of multicellular organisms in which, following the manifestation of genetic alterations, one neoplastic cell develops into a tumour mass which grows escaping all the normal rules of cell coexistence which regulates multicellular organisms. We define as malignant tumour one which spreads throughout the body forming metastases, and as benign tumour one which is localized and non-invasive. Cancer is found mostly throughout the Metazoa (i.e. multicellular animals) but is also present in some plants. A simpler neoplastic-like behaviour, so-called cheating, is present instead even in the simplest multicellular bacterial organisms, where cells can start to grow excessively, escaping normal behaviour.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115964315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DNA repair and genome integrity","authors":"G. Buscemi","doi":"10.1093/MED/9780198779452.003.0002","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0002","url":null,"abstract":"The DNA damage response (DDR) is a complex network of pathways involving hundreds of proteins with the main goal to detect and fix lesions occurring to DNA structure, thus preserving genome stability throughout generations. To enhance repair efficiency and eventually clear unrepaired harmful cells, the DDR has under its own control the progression of cell cycle, the induction of cellular senescence and the apoptotic programme. Furthermore, cells take advantage of DDR to manage break-like structures, such as telomeres, and to check processes involving DNA ‘cut and paste’ steps like meiosis and immune response. Since all these aspects of a cell life are frequently altered in cancer, not unexpectedly, deregulation of DDR is an essential step during carcinogenesis. Indeed, even if mutations in DDR genes partially reduce the repair ability of a precancerous cell, they also enhance the possibility of oncogene mutation, allow hyper-replication and promote cell survival and adaptation in stressed conditions. On the other side, impairment of DNA repair sensitizes cancer cells to radio and chemotherapeutic agents inducing DNA damage and DDR components are promising targets to enhance therapy efficiency.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"130 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115165398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Viral carcinogenesis","authors":"D. Dittmer, B. Damania","doi":"10.1093/MED/9780198779452.003.0006","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0006","url":null,"abstract":"Between 20 and 30% of human cancers are caused by infectious agents. These can be multicellular parasites, bacteria, or viruses. Whereas bacteria and parasites cause cancer by indirect mechanisms, such as inflammation and immune deregulation, viruses infect human cells directly and initiate molecular changes that lead to uncontrolled proliferation. Both DNA and RNA viruses, such as retroviruses, can cause cancer; however, the ability to promote cancer is a by-product of viral evolution and a low frequency event, often the result of faulty virus replication. Most human oncogenes, such as MYC, SRC, RAS, were first discovered because they had been pirated by retroviruses. The function of key human tumour suppressor proteins, such as RB and TP53, were identified because they bind to and are inactivated by DNA tumour viruses. Because viruses are foreign, vaccines can be devised that target them. More recently it has become possible to prevent two types of cancer caused by viruses—cervical cancer caused by human papillomavirus (HPV) and hepatocarcinoma caused by hepatitis B virus (HBV)—by preventing the initial infection using vaccination. Study of the relationship between infective agents and cancer has therefore achieved two main goals: to unravel basic mechanisms of carcinogenesis and to make some cancers preventable.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125066253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxygen and cancer","authors":"A. Harris, M. Ashcroft","doi":"10.1093/MED/9780198779452.003.0018","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0018","url":null,"abstract":"Oxygen is required for most multicellular, aerobic organisms to survive and function. The vasculature provides the conduit for delivering oxygen via haemoglobin in the blood to organs, tissues, and cells. In diseases such as cancer, low tissue oxygenation or hypoxia occurs in solid tumours because of an inadequate supply of oxygen due to aberrant tumour vasculature. Hypoxia is a key feature of most solid tumours and underlies many of the processes associated with how cancer progresses; including tumour cell survival and proliferation, genetic instability, immune responses, angiogenesis, invasion and metastasis, and metabolic adaptive responses. Solid tumours contain several different cell types that respond to hypoxia within the tumour microenvironment. Hypoxia-inducible factors (HIFs) are a highly evolutionarily conserved family of dimeric transcription factors that are central to mediating the cellular response to hypoxia by regulating the expression of a diverse array of targets. Hypoxia and HIF activation is associated with treatment failure, resistance, and poor clinical outcomes. This chapter will provide an overview of the role of hypoxia in cancer, outline the methods used to measure hypoxia clinically, and discuss the impact of hypoxia on current front-line therapies being used to treat cancer.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126414198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conclusions: Cancer biology, a moveable feast","authors":"D. Kerr, F. Pezzella, M. Tavassoli","doi":"10.1093/MED/9780198779452.003.0032","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0032","url":null,"abstract":"The increasing amount of knowledge we are acquiring has improved our understanding of cancer biology and the way we classify tumours in clinical practice in order to provide a personalised, more effective treatment. Tumours include a large number of different types of abnormal growths. The main division, into benign and malignant, is based on the ability of a neoplastic lesion to produce metastases during the natural course of the disease. Malignant tumours are a heterogeneous group of lesions, which are brought together under the generic name of cancer and its synonymous. Although we recognize a tumour as malignant intuitively, to be able to define choose, and describe what are the basic characteristics common to all the types of cancers is challenging and it could be argued whether it is actually possible and/or correct to attempt it. Recent breakthroughs in biology have certainly improved our knowledge of cancer and the treatment available. However, we are also constantly unveiling new layers of complexity that need development of new tools in order to be dealt with.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"31 37","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132845201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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