PCC2 Neoplastic Diseases - Cancers

Neoplasia (or neoplastic disease) An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Benign neoplasms Not cancerous - Whilst localised, they may still result in death, but not from spread to multiple organs. Malignant neoplasms Cancerous Metastases Cancer that grows at a distance from the primary site of cancer. Metastatic cancer Cancer that spreads to other parts of the body. What is the most common cell type among cancers ? Epithelial cancers - Carcinomas What are cancers of mesoderm cells know as ? Sarcomas What are cancers that occur in glandular tissues known as ? Adenocarcinomas Cancer hallmarks - Autonomy from growth signals Mutations affect signal pathways = cancer cell growth does not require 'normal' growth factor signalling. Cancer hallmarks - Evasion of growth inhibition Mutations affect signal pathways so that they are reduced or are ineffective. Cancer hallmarks - Unlimited replication - Under normal circumstances cells have a pre-programmed no. of cell divisions before they die = senescence - The loss of telomeres from the chromosome ends is prevented Mutations prevent cellular adhesion and Cancer hallmarks - Invasion/metastases can increase enzymes involved in invasion. Cancer hallmarks - Angiogenesis Growth of new blood vessels = stimulated by cancer cells/tumours, to maintain 1/8 nutrient supplies as the tumour increases in size. - Apoptosis is the 'natural' cell death mechanism Cancer hallmarks - Evasion of cell death - Cancer cells evade the apoptotic signals - Autonomy from growth signals - Evasion of growth inhibition - Unlimited replication What are the hallmarks of cancer ? - Invasion/metastases - Angiogenesis - Evasion of cell death - Inflammation - Genomic instability What factors induce hallmarks of cancer - Mutations ? They help provide the environment for cancer cells to develop and grow. How can we distinguish between tumours ? Invasion and spread of cells from their origin, allows us to distinguish malignant and benign tumours. - A single cell can mutate and become the dominant cell type. - Cell can undergo additional mutations, Why is Cancer often referred to as clonal so the dominant cell type may change disease ? over the course of the disease - These cells are likely to be resistant to chemotherapy 2/8 Explain why the cancer likelihood increases with age ? Cancer is a consequence of alterations to DNA ranging from simple single point mutations to more catastrophic chromosomal deletions, rearrangements or translocation. These alterations accumulate over time. 1. Proliferation 2. Cell death = apoptosis, necrosis, auWhat 3 main processes control the numtophagy ber of cancer cells ? 3. Differentiation = how specialised the cell is Differentiation Describes how similar to normal cells the cancer cells are. - Look and behave like the normal cells of the tissue that the cancer has arisen from. Well-differentiated cancer cells - Tumours that contain well-differentiated cancer cells = generally slow-growing, less aggressive. - Often look immature - Don't resemble the tissue of origin Undifferentiated cancer cells - Tumours containing undifferentiated/poorly differentiated cells often grow more quickly - Tumours are more likely to spread + have a poorer prognosis Proto-oncogenes Formed by mutations that occur in normal cells. Oncogenes 3/8 Genes mutations result in production of higher levels or higher activity protein products = oncogenes. Tumour suppressor genes Inhibit cell growth and tumour formation. Epidemiology - Environmental Best known environmental factor related to cancer = sunlight - exposure to UV radiation. In 1775 - noted the higher incidence of What environmental factor linked to cannasal and scrotal cancers in chimney cer did Percival Potts observe ? sweeps, from chronic soot exposure. - Highly varied and relate to hormone exposure and and factors = impact when exposure to hormone changes occur - Higher rate of breast cancer in nuns, reduced rate of breast cancer in women with children Epidemiology - Reproduction - Age of the first child and use of hormone therapies all impact on cancer occurrence - Use of condoms can reduce the transmission of HPV and HIV = reduces their associated cervical cancers Epidemiology - Diet - In migrants their diet changes to match the local population = their cancer profile reflects the local population - e.g., there is higher prevalence of stomach cancers in Japan Japanese population who migrated to Hawaii now has similar stomach cancer rates to that of the local Hawaiian population - Chronic alcohol intake increases the risk of cancer Epidemiology - Alcohol 4/8 - Synergistic with smoking, risk is more than additive - A lifestyle choice impacting on cancer = smoking cessation Epidemiology - Smoking - Linked to several cancers e.g., lung cancer, bladder cancers - Linked to approximately 40% of all lung cancer deaths - Reducing occupational exposure = exposure limits for carcinogens/use of sunblock in outdoor workers Ways to reduce cancer risk due to lifestyle ? - Use of barrier contraceptives and Human papilloma virus (HPV) vaccine - Adopting a Mediterranean style diet - Reduced alcohol intake/abstinence - Smoking cessation An agent that can cause cancer in humans . Carcinogens - Radiation Classifications of carcinogens ? - Chemical - Infections Radiation carcinogenicity Related to the level of energy released and the subsequent amount of DNA damage. Ionising radiation Damages DNA by direct ionisation of DNA atoms or indirectly by generating, via radiolysis, reactive oxygen species. 5/8 UV radiation Produces a unique mutation not seen anywhere other than in skin cancer. Chemical carcinogens MOA - Electrophilic forms interact with nucleophilic sites in the DNA base pair rings - Can be direct effect or - After they have been metabolised by cytochrome p450 enzymes in the liver 1. Polycyclic aromatic hydrocarbons; coal tar, benzopyrene 2. Aromatic amines; from cooked meats. 3. Azo dyes. 4. Nitrosamines and nitrosamides; from smoked fish. What are the 10 types of chemical car- 5. Hyazo and azoxy compounds. cinogens ? 6. Carbamates. 7. Halogenated compounds. 8. Natural products. 9. Inorganic carcinogens. 10. Miscellaneous compounds; alkylating agents e.g. mustard gas, asbestos Carcinogens - Infections - Can be both viral and bacterial - e.g., HPV, HIV, Epstein Barr virus and Hepatitis B and C viruses - Bacterial infections = Helicobacter pylori and S.typhi Non-modifiable factors Factors which you cannot alter, they are generally inherited. 6/8 Development of Hereditary cancers Epidemiology of hereditary cancers ? - People who inherit mutations are already part-way to cancer development and have an increased susceptibility to cancer - Genes are referred to as high penetrance genes = usually result in clinically important disease e.g., BRCA1 and BRCA2 with breast and ovarian cancers - Low penetrance genes are less likely to cause such manifestations e.g., CHEK2 and PALB2 Inherited forms of cancer represent around 5-10% of all cancers, including the most common cancers, e.g., breast and colorectal. - Raising awareness of specific cancer early symptoms is a key approach Importance of early detection in cancer ? - Screening may allow earlier detection and improve outcome (morbidity) / or survival (mortality) A process of identifying apparently Screening definition according to the Nahealthy people who may be at increased tional Screening Centre ? risk of a disease or condition. Cancer screening - Used to allow earlier detection and improve outcome (morbidity) / or survival (mortality) - Does not reduce an individuals' risk of getting cancer - Screening will not diagnose a cancer - Used to protect against cervical cancer - Part of the childhood vaccination programme = all girls ages 12-13yrs are 7/8 Human papilloma virus vaccine offered the vaccine - Vaccine is given at a younger age since exposure to virus is unlikely (sexual transmission) 8/8