{"title":"Immunotherapy and tumour resistance to immune-mediated control and elimination","authors":"G. Monnot, P. Romero","doi":"10.1093/MED/9780198779452.003.0029","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0029","url":null,"abstract":"The field of tumour immunology has gradually reached a consensus that the immune system and tumours sustain a rich set of dynamic interactions starting early during carcinogenesis. Incipient tumours may be eliminated by the immune system via adaptive immune responses mediated mainly by cytotoxic CD8 T lymphocytes, which recognize short antigenic peptides presented by polymorphic major histocompatibility complex (MHC) class I molecules. Advanced tumours, however, are generally highly resistant to the main effectors of the immune system. Moreover, the molecular and cellular composition of the tumour microenvironment is strongly immunosuppressive. Recent research efforts have focused on the dissection of the mechanisms operating at the tumour sites, which neutralize antitumour immunity in both experimental models and directly in cancer patients. All along this basic research, translational scientists have tried to harness the immune system to design novel therapeutic modalities that have collectively been coined as cancer immunotherapy. The overall goal has been to increase the numbers of tumour antigen-specific T cells in cancer patients via either vaccination or adoptive transfer of large numbers of immune cells. It is safe to state that cancer immunotherapy will provide a revolution in the treatment of cancer and the future may bear the prospect of effective tumour control in many cancer types, and that immunotherapy will be one of the main components of effective therapeutic options.","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":"115605905","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":"Biological effect of radiotherapy on cancer cells","authors":"A. Dubrovska, M. Krause, M. Baumann","doi":"10.1093/MED/9780198779452.003.0030","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0030","url":null,"abstract":"Radiation therapy is a mainstay for curative treatment of many types of tumours. The cure rate of radiation therapy depends on its ability to induce non-repairable DNA damage leading to cellular death or loss of proliferative capacity. In addition to clinical factors, efficacy of radiation therapy has been explained by the radiobiological concept of 4R parameters summarized by Rodney Withers in 1975, which include Repair of DNA damage, Repopulation, Redistribution of tumour cells in the cell cycle, and Reoxygenation. This chapter reviews the direct and indirect effects of irradiation on cancer cells, mechanisms of DNA repair and radiation-induced cell death, and also discusses implementation of the cancer stem cell model for the radiobiological concept of tumour radioresistance.","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":"124557508","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":"Genetics and genetic instability in cancer","authors":"M. Glaire, D. Church","doi":"10.1093/MED/9780198779452.003.0004","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0004","url":null,"abstract":"\"The Integrity\"of the human genome is under continual threat from endogenous and exogenous mutagens, and as a result of errors introduced during DNA replication. As the lesions generated by these processes, if left uncorrected, may lead to deleterious mutations, cells employ several sophisticated mechanisms to both prevent and repair such genomic damage. Failure of these repair mechanisms, leading to genomic instability, is common in cancer, and has even been suggested to be a universal characteristic of malignancy. This chapter outlines these cellular processes and reviews the both the mechanisms and consequences of their dysregulation in human cancer. It also highlights the emerging evidence suggesting that genomic instability is an important determinant of tumour behaviour. Finally, it discusses the possibility that targeting genomic instability may benefit patients with genomically unstable tumours in the clinic.","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":"126184706","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":"Proteomics and metabolomics applications in cancer biology","authors":"P. Cutillas, B. Kessler","doi":"10.1093/MED/9780198779452.003.0025","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0025","url":null,"abstract":"Methodologies for proteomics and metabolomics are providing an unprecedented wealth of insights into cancer molecular biology. Although different techniques for proteomics and metabolomics exist, molecular snapshots in cancer metabolism and alterations in the proteome are mainly possible due to advancements in state-of-the-art mass spectrometry technologies. In this chapter, we describe examples of how proteo-metabolomic approaches are contributing to our understanding of the molecular biology of cancer progression, signalling, survival mechanisms, angiogenesis, and metastasis. We also provide an overview of the translational information (including biomarkers) and clinically relevant insights that proteomics and metabolomics strategies may be able to deliver, despite limitations and technical challenges that still exist. A better understanding of cancer progression and an improvement of clinical outcomes will benefit from precision medicine initiatives, in which appropriate application of proteo-metabolomic methods are key for their success.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"71 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":"126204988","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":"Cancer systems biology: From molecular profiles to pathways, signalling networks, and therapeutic vulnerabilities","authors":"L. Verbeke, S. V. Laere","doi":"10.1093/MED/9780198779452.003.0026","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0026","url":null,"abstract":"Cancer systems biology encompasses the application of systems biology approaches to cancer research. Historically, systems biology was first applied in cancer research to enable a pathway-oriented interpretation of gene expression data and this strategy has undoubtedly delivered relevant insights with respect to many aspects of cancer biology. Nowadays, cancer is regarded as a complex system that integrates signals from different levels (i.e. (epi)genomics, transcriptomics, micro-environment) through a network of interconnected proteins to generate a biological response. This holistic approach not only allows the identification of new and relevant signal transduction pathways, but also provides a better understanding of several key properties of cancer cells that can be best understood from a network-level perspective: robustness, evolvability, and plasticity. This chapter provides an overview of several key concepts of systems biology, including reference gene set libraries, network topology, and available strategies to establish biological networks. Next, these concepts are utilized to explain gene set and gene network analysis with particular focus on cancer biology. Finally, the caveats and challenges that are facing cancer systems biology are summarized.","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":"129360431","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":"Invasion, metastasis, and tumour dormancy","authors":"A. Ugolkov, A. Mazar","doi":"10.1093/MED/9780198779452.003.0019","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0019","url":null,"abstract":"Tumours can be either benign or malignant. A first difference is that the primary malignant tumour infiltrates the surrounding tissue while, with very few exceptions, the benign tumours do not infiltrate. The second and main one is that, by definition, the malignant tumours are able to produce metastatic lesions in other organs. Finally, metastases can declare themselves even after period of years from the appearance of the first lesion. This is because of the third property of the malignant cells i.e. their ability to spread and then do not immediately grow into a detectable metastasis, but to be ‘dormant’ for a variable period.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"37 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":"122369695","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":"Radiation as a carcinogen","authors":"Y. Xiang, C. Qian","doi":"10.1093/MED/9780198779452.003.0008","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0008","url":null,"abstract":"The data from animals, cell lines, and humans have led to the consensus of induction of carcinogenesis by ionizing radiation, especially at low-level doses, and that there is a dose–response relationship between radiation and cancer incidence. However, additional factors, including radiation type, dose rate, specific tissues, and animal species, also provide a contribution. The development of molecular biology research has helped explain the mechanism of radiation carcinogenesis, including pathway activation and chromosome alterations. Bystander effects and abscopal effects are additionally characteristics of radiation carcinogenesis. This chapter takes a look at how radiation, from both environment and industry, has contributed to cancer incidence over the past century.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"7 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":"115780491","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":"Chaperones and protein quality control in the neoplastic process","authors":"A. Rasola","doi":"10.1093/MED/9780198779452.003.0017","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0017","url":null,"abstract":"Maintenance of proteome quality control in cells is a vital and extremely complex task, which requires fine-tuning among synthesis, folding, and degradation of proteins and is controlled by an integrated network of subcellular components. A pivotal role in this process is played by chaperones, molecular machines that take part in nearly all cellular functions and make possible the optimal activity of proteins by assisting their folding, conformational changes, and subcellular trafficking, and by controlling protein degradation following unfolding, misfolding, or aggregation.\u0000 Neoplastic cells undergo major changes in the homeostasis of their proteome, or proteostasis, as a consequence of a profound rewiring of their metabolic circuitries and of exposure to stressful environmental stimuli, such as hypoxia or nutritional and pH fluctuations. These stress conditions also affect protein folding in the endoplasmic reticulum and mitochondrial bioenergetic functions, leading to activation of organelle-restricted, protective signalling pathways called unfolded protein responses, which can subtly regulate the equilibrium among death, dormancy, and aggressiveness of tumour cells. In most cancer types molecular chaperones are overexpressed and exploited to cope with these stress stimuli and to underpin pro-oncogenic biological routines, including cell growth, proliferation, invasion, metastasis, and escape to death stimuli. Chaperone induction has been associated with cancer progression, resistance to chemotherapy, and poor prognosis; therefore, development of chaperone-targeting drugs has emerged as a promising antineoplastic strategy.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"10 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":"127020815","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":"Oncogenesis and tumour suppression","authors":"M. Tavassoli, F. Pezzella","doi":"10.1093/MED/9780198779452.003.0011","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0011","url":null,"abstract":"Two sets of genes are among the major driver of tumours, both malignant and benign: the oncogenes and the tumour suppressor genes. Oncogene refers to a gene that encodes for a protein (oncoprotein) in which excessive and unregulated activity can transform a normal cell into a cancer cell. As it is necessary for just one of the two gene copies to be abnormal, oncogenesis is defined as dominant. Tumour suppressor genes are known for their roles in inhibiting cell growth and have antitumour effects. According to the classic model, growth suppressor genes are recessive and therefore both copies have to be inactivated in order for an effect to be seen. Exception however occurs! Recently also non-coding mRNAs (i.e. an mRNA that is not translated into a protein) have been found to be able to induce oncogenic and suppressive effects. Finally, both some genes and some non-coding mRNA are able, in certain cellular contexts, to behave both as both an oncogenic and a suppressive factor.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"94 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":"125981745","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":"Evolution and cancer","authors":"T. Dønnem, K. Micklem, F. Pezzella","doi":"10.1093/MED/9780198779452.003.0003","DOIUrl":"https://doi.org/10.1093/MED/9780198779452.003.0003","url":null,"abstract":"Evolution is the process by which living organisms change through time, and natural selection is the process which leads some organisms to thrive and others to die out. Evolutionary medicine tries to explain why traits leading to susceptibility to disease get maintained or even positively selected. Cancer, being a genetic disease, can be analysed as an example of evolution by natural selection. The observation that humans in developed societies have much higher rates of cancer can be analysed and explained by an evolutionary approach. At a cellular level, tumours are made up by a population of cells continuously growing and mutating while interacting with the microenvironment of the body. Thus, the mechanism of changes in individual tumours is the process of natural selection. Evolutionary biology is now increasingly used to better understand tumour growth and therefore to improve treatments.","PeriodicalId":417236,"journal":{"name":"Oxford Textbook of Cancer Biology","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128671050","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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