Neoplastic Disease Intro Wk 4 Flashcards
Outline the main principles of the Clonal Evolution and Cancer Stem Cell models of tumour formation, and explain their potential significance in relation to cancer treatment
Clonal: all cells in a tumour are of single origin, any cell is a target (random), driver cells can be propagated (have a growth advantage) daughter cells have compounding proliferation/driver advantage. All new driver mutations have potential to create tumours at different stages. Remove all.
Stem: Only stem cells can create tumours (are drivers). Growth advantages are limited to stemcells (decreased). Differentiation decreases proliferation. Can undergo symmetrical and asymmetrical cell division. Malignancy is still possible, though via a hierarchy model ie only stem cells can create new tumours. Remove only stem cells.
Where to check for metastasizing cancer
Clinical diagnosis of metastasis in local lymph node.
Explain malignant
Neoplasm ability to spread to surrounding tissue, blood, lymphatic tissue.
Explain cancer
Malignant neoplasm
Explain tumour
Swelling or mass, commonly all types of neoplasms.
What is the order of cell differentiation from pluripotent to differentiated cell?
Pluripotent -> multipotent and oligopotent -> precursor -> differentiated.
What is the order of cell differentiation and maturation from pluripotent to differentiated cell?
Pluripotent -> multipotent and oligopotent progenitor cells -> precursor -> differentiated.
What changes in a cell as it matures and differentiates?
Cell phenotype: morphology, function and behaviour.
What regulates cell phenotype?
Intrinsic and extrinsic factors
How do intrinsic and extrinsic factors regulate cell phenotype?
Intrinsic: gene expression and protein function
Extrinsic: growth factors, signalling molecules
How do intrinsic factors alter cell phenotype in neoplastic disease?
Abnormalities in genetic factors
How do intrinsic and extrinsic factors regulate cell phenotype?
Intrinsic: gene expression and protein function
Extrinsic: growth factors, signalling molecules
What is the 3-step process of how how a neoplastic disease occurs?
- Multiple genetic and or epigenetic changes
- Altered protein expression and or function
- Altered cell function and behavior.
What is the difference between driver and passenger genes?
Driver genes drive critical genes towards concern phenotype
Passenger genes are neutral to the process; and do not control (drive) the gene.
How many driver genes need to be mutated to create a cancer cell?
Three to Seven genes
What do genetic mutations and epigenetic changes cause?
Altered expressions of genes and their products, leading to loss or gain of cell function.
What do mutations in genes cause?
Loss or gain of function of mutated protein products
What is the affect of proteins with altered function?
Alters pathways and process in the cell, leading to phenotypic changes and the development of behaviours characteristic of cancer cells
Do extrinsic factors contribute to the regulation of gene expression in neoplastic cells?
Yes. growth factors, signalling molecules
What’re the six hallmarks of cancer?
- Self-sufficient growth
- Insensitivity to anti-growth signals
- Evasion of apoptosis
- Limitless replicative capacity
- Sustained angiogenesis (growth of blood vessels into the tumour)
- Tissue invasion & metastasis
What are the genes which encode proteins which stimulate cell growth and division collectively called? What are they called when mutations occur in these genes?
Protooncogenes
Oncogenes [cancer causing genes]
What are the genes which encode proteins such as growth factors which stimulate cell growth and division collectively called? What are they called when mutations occur in these genes?
Protooncogenes
Oncogenes [cancer causing genes]
What are the name of the proteins and the genes which produce them called which function to inhibit progression through the cell cycle called?
Tumour suppressor proteins
Tumour suppressor genes
What has to happen to chromosomal strands for a cell to undergo loss of function? How does this occur intrinsically and extrinsically?
The gene on both chromosomal strands (both alleles) needs to be inactivated (two hits). This occurs intrinsically by point mutations, rearrangements, insertions or deletions in the gene DNA sequence, or large deletions resulting in complete loss of the gene. Extrinsically, (epigenetically) a gene may be silenced due to methylation.
What are a cancer cell’s behavioural changes?
Uncontrolled proliferation due to oncogene activation and tumour suppressor gene inactivation.
Avoidance of cell death, immortality and functional changes to facilitate invasion, metastatic spread and survival.
What are three fundamental key points about tumour development?
- Clonal origin
- Heritable genetic/epigenetic changes alter cell behaviour.
- Multistep process involving multiple hits affecting multiple driver genes
