Abstract
With more than half of all cancer cases occurring in less developed nations of the world, cancer is a source of significant and growing mortality worldwide, with an increase to 19.3 million new cancer cases per year projected for 2025. Standard current treatments for cancer include surgery, radiotherapy, and a host of other systemic treatments comprising cytotoxic chemotherapy, hormonal therapy, immunotherapy, and targeted therapies. Referred to as the “guardian of the genome,” the alteration or inactivation of p53 tumour-suppressor gene by mutation or by its interactions with oncogene products or DNA tumour viruses can lead to cancer. The p53 is mutated in about half of almost all types of cancer arising from a wide spectrum of tissues. This chapter focuses on several types of cancer including breast and ovarian, colorectal, small cell lung carcinoma, malignant melanoma, pancreatic, prostate, neurofibromatosis, multiple endocrine neoplasia, and retinoblastoma.
TopChapter Outline
14.1 Overview
14.2 p53 Tumour Suppressor Gene
14.3 Breast and Ovarian
14.4 Colorectal
14.5 Lung Carcinoma (small cell)
14.6 Malignant Melanoma
14.7 Pancreatic
14.8 Prostate
14.9 Neurofibromatosis
14.10 Multiple Endocrine Neoplasia
14.11 Retinoblastoma
Chapter Summary
TopLearning Outcomes
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Identify each type of cancer
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Outline the symptoms of each type of cancer
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Explain the genetic basis of each cancer
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Summarize the therapies available to treat each cancer
Top14.1 Overview
With more than half of all cancer cases occurring in low- or middle-income nations of the world, cancer is a source of significant and growing mortality worldwide, with an increase to 19.3 million new cancer cases per year projected for 2025 (Block et al., 2015). Standard current treatments for cancer include surgery, radiotherapy, and a host of other systemic treatments comprising cytotoxic chemotherapy, hormonal therapy, immunotherapy, and targeted therapies. Today cancer continues to frustrate clinical treatment efforts, but the search for effective therapies is a never-ending research goal. (Palumbo et al., 2013; Block et al., 2015) Of the global cancer burden, it is estimated that over 20% is attributable to infectious agents. In contrast to virally induced cancers, bacteria have been largely neglected as factors contributing to cancer, with only a few bacterial infections linked to cancer development to date. Bacteria may contribute to cancer development through inflammation, induction of DNA damage by toxins, metabolites, and/or manipulation of host cell signalling pathways during their infection cycle. (Zur, 2009; Samaras et al., 2010; Coghill & Hildesheim, 2014)
Molecular target therapies represent a significant advance in the treatment of cancer and include a variety of drugs like: 1) Imatinib, an inhibitor of the tyrosine kinase enzyme BCR-ABL, which has made chronic myelogenous leukaemia a more manageable disease; 2) Sunitinib, sorafenib and bevacizumab are inhibitors of vascular endothelial growth factor receptor used in renal and colon cancers; 3) Gefitinib and erlotinib are based on tumour-specific targets and are epidermal growth factor receptor inhibitors used in lung cancer, and the HER2 inhibitor trastuzumab used in breast cancer; 4) Another approach is the synthetic lethal model exemplified by the use of poly-ADP ribose polymerase inhibition, in which mutational loss of one or more redundant components of a cell survival pathway in tumourigenic cells confers selective sensitivity to drugs that target remaining pathway components. The expense of the new targeted therapies is a major limitation on their use—for example, 11 of 12 drugs approved by the USFDA in 2012 were priced above $100,000 US per year per patient, primarily because of the accelerating costs of drug development. (Vogelstein et al., 2013; Zahreddine & Borden, 2013; Ciociola et al., 2014)
Key Terms in this Chapter
Epilepsy: A neurological disorder that causes seizures.
Aromatase Inhibitors: A hormone blocking drug that works by blocking the aromatase enzyme, thereby stopping the production of oestrogen.
Arrhythmia: A disorder in which the heart beats with an irregular rate or rhythms.
Oxidative Stress: An imbalance between free radicals and antioxidants in charge of homeostasis.
Immunotherapy: A cancer treatment that helps the body’s immune system fight the cancer.
Myocardial Ischemia: The reduction of blood flow that prevents the heart from receiving enough oxygen.
Radiotherapy: A treatment used to cure or relieve the symptoms of cancer by using high-energy rays to destroy cancer cells.
Nanoparticles: A microscopic particle between 1 and 100 nanometres in size.
Tumorigenic Cells: Cells that are capable of or tend to form tumours.
Macrocephaly: A term used to describe a larger than normal head circumference at birth.
Laser Therapy: A treatment involving lasers to destroy blood vessels that surround and supply a tumour.
Mastectomy: A surgical operation involving the removal of one or both breasts to treat breast cancer.
Biomarkers: A biological characteristic that is used as an indicator of normal biological processes.
Colonoscopy: An exam of the colon and rectum using a small camera to search for polyps and colon cancer.
Positron Emission Tomography (PET): A diagnostic imaging test that uses a special dye that contains radioactive tracers which are absorbed by certain organs and tissues.
Bradycardia: Lower than normal heart rate.
T-Cell Therapy: A type of cancer treatment involving the alteration of a patient’s T-cell in order to attack cancer cells.
Lymphocyte Transfusion: A therapy that involves the introduction of donor lymphocytes to destroy remaining cancer cells.
Brachytherapy: A type of radiotherapy that involves the placement of radioactive material inside or near the tumour to treat cancers.
Next Generation Sequencing (NGS): A sequencing method used to measure large numbers of individual DNA sequences in a short period of time.
Adaptor Proteins: Proteins that facilitate the binding of a mRNA transcript by recruiting appropriate signal components such as receptors. They form complexes with other proteins to regulate signal transduction pathways.
Hormonal Therapy: A treatment used to cure or relieve the symptoms of cancer by reducing the amount of oestrogen in the body or blocking the effect of oestrogen on cancer cells.
Carcinogenesis: The process of normal cells transforming into cancer cells.
Palliation: To ease the symptoms without curing the underlying cause.
Apoptosis: Programmed cell death.
Adjuvant Treatment: Extra treatments used in addition to the main cancer treatment to prevent cancer from returning.
Single Nucleotide Polymorphisms (SNPs): A genetic variant of a single nucleotide in a DNA sequence.
Focal Therapy: The use of focal modalities to treat small tumours.
Thromboembolic Events: Occurs when a blood clot in an artery or vein breaks off and lodges somewhere else in body and obstructs blood flow of the circulatory system.
Genome-Wide Association Studies (GWAS): An observational study that examines if there is an association between genetic variants and traits in different individuals.
Magnetic Resonance Imaging (MRI): A diagnostic imaging test that uses powerful magnet and radio waves to produce images of body organs and tissues.
Scoliosis: A condition that causes an abnormal curve to the spine.
Chronic Pancreatitis: Prolonged inflammation of the pancreas.
Pericarditis: Inflammation of the pericardium, a sac-like membrane that surrounds the heart.