Neoplasms, carcinogenesis and tumour classification Flashcards
What is neoplasia?
Unregulated and irreversible clonal growth that results in neoplasm/tumour formation
Why is neoplasia described as unregulated and irreversible?
Neoplasia continues after stimulus is removed
What is a neoplasm/tumour?
Lesion formed by abnormal autonomous growth of cells that persists in absence of a stimulus
What is meant by clonal growth to form a neoplasm/tumour?
All of the tumour cells are derived from the same single cell of origin
What are the 2 types of neoplasm/tumour?
Benign or malignant
What cell types can undergo neoplastic change?
All cell types
What is the most common cell type that undergoes neoplastic change?
Epithelial cell
What 2 factors can cause molecular change of genes in carcinogenesis?
Mutagens
Ageing
What are the 2 types of genetic change in carcinogenesis?
Genetic mutation
Epigenetic change
What is epigenetic change?
Modification of genes due to environment and behaviours eg. methylation
Gene sequence itself isn’t altered
What properties do genetic errors provide to cells in carcinogenesis?
Cancer hallmarks
How many cancer hallmarks are there?
6
What are the 6 cancer hallmarks of cancer cells developed in carcinogenesis?
Resisting apoptosis
Constant proliferation
Inducing angiogenesis and immune system evasion
Enabling replicative immortality
Evading growth suppressors
Activating invasion and metastasis
What 2 characteristic features of a cancer can be identified by examining its cancer hallmarks?
Natural history
Responses to therapies
When genetic error occurs in carcinogenesis, is this a type of DNA damage?
Yes
How is a mutagen different from a carcinogen?
Mutagens can be non-lethal, but carcinogens usually result in malignant tumours (cancer)
What is a carcinogen?
Agent that causes DNA damage that increases cancer risk
Give 2 examples of chemicals that are carcinogens?
Benzene
n-nitrosamine
Why is cigarette smoke a carcinogen?
It contains benzene
What bacteria is associated with gastric adenocarcinoma and lymphoma?
Helicobacter pylori
What type of infective agent is a liver fluke, that is also a carcinogen?
Parasite
Give 4 examples of oncogenic viruses?
HPV, EBV, HCV, HBV
Give 4 types of cancers that radiation is associated with?
Skin cancer, thyroid cancer, lymphoma, leukaemia
How is a clone of neoplastic daughter cells formed in carcinogenesis?
The cell which has undergone DNA damage overcomes DNA repair mechanisms and can transmit the genetic error to daughter cells, forming a clone
What occurs in progression during the molecular sequence of carcinogenesis?
A single daughter cell from the clone mutates to have a survival advantage, so natural selection favours this aggressive daughter cell and it dominates the population by forming its sub-clone
How does a tumour form a tumour microenvironment?
The tumour recruits normal cells
Where does a tumour form its tumour environment?
In the organ that it arises from
How do DNA mutations cause tumour growth, invasion of surrounding tissues and metastasis?
DNA mutations disrupt regulatory systems
What is the most commonly mutated proto-oncogene in the human body?
RAS (Rat Sarcoma virus)
What is a proto-oncogene?
Normal gene for cell growth and differentiation, that mutates into an oncogene
Give 5 examples of proto-oncogenes?
Growth factor
Growth factor receptor
Nuclear receptor
Cell-cycle receptor
Signal transducer
What does MAP Kinase pathway stand for?
Mitogen-Activated Protein Kinase pathway
What type of receptor does the growth factor bind to at the cell membrane in the MAP Kinase pathway?
Receptor tyrosine kinase
What inner membrane protein is activated by binding of growth factor to receptor tyrosine kinase in the MAP Kinase pathway?
RAS (Rat Sarcoma virus)
In the MAP Kinase pathway, what molecule does RAS activate, and what it its function?
RAF (Rapidly Accelerating Fibroma), a signal transducer
In the MAP Kinase pathway, what molecule does RAF activate, and where is is found in the cell?
MEK, a cytoplasmic protein
In the MAP Kinase pathway, what molecule does MEK activate?
ERK
In the MAP Kinase pathway, what does ERK do after it travels to the nucleus?
Activates transcription factors controlling cell metabolism and growth
In the MAP Kinase pathway, how do the ERK-activated transcription factors affect cell-cycle proteins?
Cell-cycle proteins are switched off
When cancer arises, what step of the MAP Kinase pathway is different?
Cell-cycle proteins mutate to be permanently switched on, which causes uncontrollable transcription
What is the role of Her 2 in the MAP Kinase pathway, and what type of cancer is it amplified in?
Her 2 is a receptor tyrosine kinase that is amplified in breast cancer
What drug is given to inhibit Her 2 when it is amplified in breast cancer?
Herceptin
What type of drug is used to treat malignant melanoma, which involves the MAP Kinase pathway?
RAF inhibitor
What are tumour suppressor genes?
Genes that regulate cell growth by preventing tumour development
What hypothesis is used to explain how tumour suppressor genes are affected by DNA mutations and cause cancer?
Knudson’s two hit hypothesis
Explain how Knudson’s two hit hypothesis refers to mutated tumour suppressor genes in carcinogenesis?
Both maternal and paternal copies of the tumour suppressor gene must be mutated to cause cancer
What triggers p53 expression in a normal cell?
DNA damage
What does p53 activate to stop the cell-cycle at the G1 checkpoint?
p53 activates transcription factors to form CDKI p21, which blocks the CDK4/cyclin D, this stops cell-cycle progression
How does p53 trigger apoptosis when the cell has severe DNA damage?
Upregulates BAX, which disrupts BCL2 so that the mitochondrial membrane loses its stability and cytochrome C leaks out
What is retinoblastoma?
Tumour suppressor gene that regulates progression from G to S phase of cell-cycle
What are apoptosis regulators?
They stop normal cells from dying but promote apoptosis in mutated cells with irreparable DNA damage