This chapter examines the influence of genetics, environmental factors, and lifestyle behaviours on the risk of cancer developing. It begins by describing global cancer trends, including incidence, mortality, geographical variations, and gender variations. Cancers can be familial (inherited) or sporadic. In inherited cancers, the disease causing mutation is carried in the germline and so is present in all cells of the body at birth. This does not cause cancer on its own and additional somatic mutations are still required for cancer to develop. However, only about 5–10 per cent of all cancers result directly from gene defects inherited from a parent. The rest occur through mutations acquired in somatic cells, and are sporadic. These mutations can arise due to exposure to certain environmental factors, lifestyle behaviours, and some infectious agents as well as spontaneous mutations arising, for example through errors in DNA replication.
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Molecular Epidemiology
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Cancer biochemistry and tumour markers
Joanne Adaway and Gilbert Wieringa
This chapter describes the role of the clinical biochemistry service in the diagnosis and monitoring of patients with cancer, the contribution of cancer-specific investigations, and the unique elements of service provision compared with those seen in nonspecialist units. Routine biochemical tests can give clues as to the presence of cancer, but further investigations are required to confirm the diagnosis. The ideal tumour marker could be used in all aspects of cancer management, from screening and diagnosis to monitoring recurrence, but unfortunately the ideal tumour marker does not exist. Nevertheless, different tumour markers have been developed and these are useful in certain types of cancer. Fields such as molecular diagnostics and pharmacogenomics are increasingly being used to improve cancer diagnosis and tailor treatment to the individual patient.
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Nutrition and Cancer
Kathryn E. Bradbury and Timothy J. Key
This chapter looks at cancer, which is one of the leading causes of death worldwide. Cancers can arise in the cells of different tissues and organs in the body, therefore there are many different types of cancer, and the causes vary between sites. Epidemiological studies showing large variations in cancer rates between populations indicate that the majority of cases of cancer are, at least in theory, preventable, and that environmental and lifestyle factors, including diet, can play important roles in the development of cancer. Several major causes of cancer have been identified; the most important is tobacco, which causes cancer of the lung and many other types of cancer. Diet is thought to influence the risk of many cancers, but research to determine which dietary factors are related to risk is challenging and few dietary factors have been firmly established as causally related to cancer risk.
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Introduction
This chapter aims to provide a foundation in the molecular biology of cancer and to demonstrate the conceptual process that is being pursued in order to design more specific cancer drugs. It discusses the translation of the knowledge of molecular pathways into clinically important therapies, then introduces a foundation in the cell and molecular biology of cancer. The chapter also reviews the terminology of cancer and the mechanisms of cellular processes. The chapter then shifts to look at the intricacies of cell function and the molecular pathways that underlie the process of carcinogenesis, whereby a normal cell is transformed into a cancer cell. It ultimately considers cancer cells in the context of the entire body.
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Major Challenges and New Opportunities in Cancer
This chapter highlights the major challenges and new opportunities in the study and research of cancer. Despite the advances in the development of more targeted therapies and of new treatment modalities, a number of areas continue to challenge the successful treatment of cancer. These include metastatic tumour spread and resistance to therapy. Nevertheless, the cancer genomics revolution, combined with the development of new technologies such as single-cell analysis, has also created substantial opportunities, leading to the identification and use of biomarkers in the clinical management of cancer and enabling the monitoring of disease resistance. These in turn are facilitating the use of more personalized treatment regimes based on the molecular profile of the patient's tumour, including precision cancer medicine and cancer gene therapy. The chapter also looks at new directions in cancer immunotherapy.
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Cancer chemotherapy
This chapter highlights the importance of cancer chemotherapy. The exact cause of most cancers is still unknown, but underlying causes relate to mutations or damage to mechanisms that normally prevent errors from being passed on from cell to cell. The chapter then details the causes and classification of cancer and the common chemotherapy agents used to treat various cancers. Treating cancer poses a range of problems, mostly because it involves using drugs that are toxic to growing cells. The chapter notes how cancer cells also develop ways of avoiding the effects of chemotherapy treatment. It also considers the art in combining chemotherapy regimens.
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Clinical oncology 1: Basic concepts and common cancers
This chapter focuses on the clinical oncology of the four most common cancers — breast cancer, lung cancer, colorectal cancer, and prostate cancer — and discusses their anatomy, aetiology, presentation, diagnosis, and management. It also provides an overview of the prevention, epidemiology, and classification of these cancers. Common features of cancer management include surgery, chemotherapy, radiotherapy, or a combination of the three treatments. However, there are certain circumstances wherein radiotherapy or chemotherapy may precede surgery in an effort to weaken the tumour before it is excised. Differential diagnoses must be considered since many cancers present with general and non-specific features, such as weight loss, tiredness, and venous thrombosis.
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Cancer Genomics
This chapter discusses cancer genomics, which is one of the fastest-moving areas of medical research and is having a direct impact on people's lives. Cancer is a disease in which cells divide in excess, generating a lump, known as the primary tumour. A key feature of cancer is that the cells in the lump spread, invading the neighbouring normal tissues and blood and lymphatic vessels, allowing them to colonize distant organs, forming distant secondary tumours. Both primary and secondary tumours may cause symptoms as they penetrate and grow into normal tissues. The genome changes in cancers include single nucleotide changes, amplifications or deletions of regions of chromosomes, and chromosome rearrangements that may join genes together. The chapter considers how understanding the genome of cancer cells can help us prevent and treat cancer, and improve the survival and quality of life of patients.
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Cancer Fundamentals
This chapter provides an overview of the fundamentals of cancer. Normal cells evolve to become cancer cells by acquiring successive mutations in primarily two classes of genes: the proto-oncogenes and the tumour suppressor genes. Mutations that specifically drive cancer development and disease progression are called driver mutations; the rest are termed passenger mutations and their role in carcinogenesis is less clear. Large-scale cancer genome studies have provided deep insight into the mutational profile of the cancer genome, and are presently informing not only basic research but also the clinical management of cancer patients. The chapter then looks at cancer stem cells, which have the capacity to self-renew and differentiate into cell types that recreate the cellular heterogeneity of the tumour from which they derive. Viruses are also associated with the development of some cancers as are certain bacteria.
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Clinical oncology 2: Further types of cancer
This chapter covers the fifth to sixteenth most frequent cancers that together cause a third of all cancer deaths. It discusses the aetiology, presentation, diagnosis, and management of pancreatic cancer, oesophageal cancer, bladder cancer, liver cancer, stomach cancer, brain cancer, renal cancer, ovarian cancer, oral cavity and throat cancer, cancer of the uterus, melanoma, and mesothelioma. From a public health perspective, the cancers of defined organs and tissues described in this chapter have been focused upon in medical science simply because they are the most frequent and comprise 84% of all cancer deaths in 2021. The chapter notes that multiple endocrine neoplasia (MEN) occurs in many different organs and is often described as having two types with a familial component. The chapter considers the difficulty of diagnosis for malignant neoplasms.
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Cancer diagnosis and screening
This chapter focuses on cancer diagnosis and screening. It explains that cancer is usually treatable if found early enough, so warning signs and symptoms should not be ignored. Population screening for common cancers is an important and alternative way of detecting cancer. Diagnosis depends heavily on molecular characteristics of a tumour as these allow medical professionals to determine the optimum type of therapy needed. They also give information on predicting the development of the disease (prognosis). The chapter highlights that accurate diagnosis is necessary for optimal patient management. In cancer, it is not easy to get the perfect screening test since under-diagnosis can cost lives, while over-diagnosis causes unnecessary anxiety and intrusive treatment.
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Cancer—a multitude of diseases
This chapter examines the notion of cancer as a multitude of diseases. It shows that benign tumours are not classified as cancer because they do not metastasize and spread around the body to other organs. Prognosis depends on the type, grade, and stage of a tumour and its response to treatment. The chapter explains that cancer is a multistep process that requires multiple genetic and epigenetic changes to occur in cells that also need time to develop. It then provides an overview of the hallmarks of cancer, citing that different cancers share several common traits despite being a diverse set of diseases.
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Pathology of Cancer
This chapter discusses the pathology of cancer. Tumours are behaviourally classified as benign or malignant based on characteristics identified by the physician, pathologist, or radiologist. In addition to benign or malignant, a further important classification that determines treatment and prognosis is the morphological classification. This is based on the type of malignant cell and its degree of differentiation. There are various stages in diagnosis of solid tumours, starting with gross examination and then imaging, and finally histology. Meanwhile, cancer screening involves looking for cancer before a person has any symptoms, with the aim of catching cancer at an early stage when it is easier to treat. Douglas Hanahan and Robert Weinberg first coined the term 'hallmarks of cancer' in 2000 to describe the essential biological processes necessary for tumour formation. These hallmarks are generalized features that are considered fundamental to cancer cell biology.
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Cancer Treatment and Clinical Management
This chapter presents an overview of cancer prognosis and current treatments such as surgery, radiotherapy, and chemotherapy. It begins by looking at cancer prevention. Predicting the expected outcome for patients diagnosed with cancer is a critical step in their management; however, prognostication has remained somewhat subjective, leading to suboptimal clinical outcomes. The chapter then considers immunotherapy, which aims to treat cancer by generating or enhancing an immune response against the tumour. Immunotherapy differs from other methods of cancer treatment in that it does not target the tumour cell directly but instead targets the immune system. Principally, three strategies are utilized: immune checkpoint blockade, adoptive T cell transfer, and cancer vaccines. The chapter also describes how clinical trials of new candidate drugs are currently undertaken.
Book
Aysha Divan and Janice A. Royds
Cancer Biology and Treatment starts off by describing the fundamentals of canceras a disease of the genome. It then looks at the pathology of cancer. It also examines molecular epidemiology and looks at key players and pathways in cancer. Cancer treatment and cancer management are important topics to consider in this field. Finally, the text looks at major challenges and new opportunities in the study and research of cancer.
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Cancer stem cells and the regulation of self-renewal and differentiation pathways: focus on colon cancer and leukemias
This chapter begins with an overview of the process of differentiation during development and in the adult. It outlines the characteristics of cells at different degrees of differentiation and discusses their relationship to cancer. The chapter also covers the review of the “cancer stem cell model” that states that subpopulations of cells with stem cell properties initiate and maintain the cancer phenotype. These cells often reside in distinct microenvironments in tumors, called stem cell niches. Signals from the stem cell niche dictate stem cell fate and behaviour. The chapter then reviews the molecular mechanisms that underlie the regulation of self-renewal and examines specific mutations in these pathways that can lead to cancer. Finally, the chapter elaborates on the new cancer therapeutics designed to target aspects of self-renewal and differentiation pathways.
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Epithelial Tumours and Melanoma
Manuel Rodriguez-Justo
This chapter focuses on epithelial tumours and melanoma. It explains that epithelial tumours growing from the lining layer of internal organs or skin are called carcinomas while melanomas arise from melanocytes found in the epidermis, hair follicles, eyes, and brain. Moreover, the chapter discusses the epidemiology and tumour types of colorectal cancer, lung cancer, gastroesophageal cancer, and melanoma. It also explores the signalling pathways in epithelial carcinogenesis. The chapter then includes the most common molecular abnormalities found in epithelial cancers and melanoma along with their therapeutic implications. It notes the possible effect of immuno-checkpoint inhibition in melanoma and epithelial tumour treatments.
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Analytical immunocytochemistry
Guy Orchard, David Muskett, and Anne Warren
This chapter describes how immunocytochemistry (ICC) can be employed in the investigation of pathological states. It begins by explaining malignancy, which is defined by a change in the normal cell biology of cells. It results in an abnormal growth or tumour that can then spread (metastasize) to other body sites. Within histopathology, there are recognized key malignant tumour groups, including carcinoma, lymphoma, melanoma, mesothelioma, and sarcoma. The chapter then looks at the key antibodies used in ICC, before focusing on the investigation of breast cancer, lung cancer, and prostate cancer. It also discusses the use of ICC in the investigation of lymphoma; how ICC can contribute to the identification of tumours of an unknown primary malignancy, the role of ICC in the investigation of autoimmune skin disease, and the role of ICC in the strategy of patient management targeted therapies.
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Cancers
Kathryn E. Bradbury, Aurora Perez-Cornago, and Tim J. Key
This chapter focuses on the pathophysiology of cancer before considering the incidence of cancer worldwide and in the UK. Cancer refers to a disease in which the normal control of cell division is lost so that an individual cell multiplies inappropriately to form a tumour that eventually spreads and causes death. Cancer can arise from the cells of different tissues and organs in the body, so there are many different types of cancer. The chapter shows that the causes of cancer in different parts of the body vary while referencing the impact of tobacco, alcohol, ionizing radiation and ultraviolet light on the body. It considers the epidemiological data linking diet with cancer.
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A Breath of Fresh Air
This chapter explores the anatomy and physiology of the respiratory system. It examines the mechanics of ventilation while also elaborating on the division of the respiratory system into upper and lower respiratory tracts. Both the upper and lower respiratory tract are very vulnerable to smoking-related damage, as they directly receive inhaled smoke from cigarettes and other tobacco products. The chapter cites how cancers, the best-known and most feared diseases which affect the gas exchange system, can occur at any level of the respiratory tract. It then explains how surgery aims to improve quality of life through tonsillectomies or can be life-saving, when it comes to a lung transplant.
