Cancer 2 Flashcards
What is cancer?
Broad complex group of diseases characterised by uncontrollable growth of cells which do not die
Why do cancers tend to occur in older patients?
There is more time for accumulation of genetic changes
Name 6 major hallmarks of cancer
- Sustaining proliferative signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Inducing angiogenesis
- Resisting cell death
Name 4 proteins in cytoplasm which have cell cycle control
- Cyclins
- Cyclin dependent kinases (CDKs)
- Cyclin dependent kinase inhibitors (CKIs)
- Anaphase promoting complex (APC)
Describe 3 cytoplasm proteins which are affected in a tumour cell
- Over expression of cyclins
- Over expression of CDKs
- Deactivation of CKIs
Describe a major characteristic of tumour cells with regards to cell division but unrelated to the major cytoplasm proteins
Abnormality of checkpoints
What are 2 genes which cause sustained proliferative signalling?
- Activation of oncogene
2. Inhibition of tumour suppressor genes
Describe oncogenes
- Dominant
- Encourage cell division
Name 3 types of hyper activation of genes which promote growth
- Gene fusions / translocations (BCR-Abl)
- Point mutations (KRAS)
- Amplification (HER2)
Describe tumour suppressor genes
- Recessive
- Keep cell growth under check
- Can repair damage or stop cell dividing
Name 4 ways tumour suppressor genes can be altered
- Point mutations
- Deletion of regions of chromosomes
- Loss of heterozygosity
- Altered methylation of promoter
Describe familial cancer syndromes
- Recessive at a cellular level but dominant with regard to cancer risk
- Point mutation knocks out recessive gene
- Only one more gene must be knocked out instead of 2
What is Li-Fraumeni Syndrome caused by?
Mutation in p53
Describe the familial form of retinoblastoma
- Child inherits one mutant copy of Rb1 gene
- Disease occurs earlier
- Higher probability of disease occurring in 2 eyes
- Tumour may be multi-focal and bilateral
Describe the sporadic form of retinoblastoma
- Mutation has to occur in both copies of Rb1 gene
- Unlikely for 2 mutations in more than one cell
- Tumour occur later in life
- Tumours are likely to be unilateral
Name 4 stresses on a cell which normally causes p53 activation
- DNA damage
- Hypoxia
- Heat / cold shock
- Mitotic spindle damage
Name 4 outcomes triggered in a normal cell by p53 activation
- Cell cycle arrest
- DNA repair
- Apoptosis
- Senescence
How does HPV affect p53 gene?
HPV encodes a protein which binds to and inactivates p53
How do cancers tend to activate invasion and metastasis?
Cell-Extracellular matrix interactions are altered
Name 4 ways cell-extracellular matrix interactions are altered
- Changes in structural proteins (integrins)
- Up regulation of enzymes for tissue break down (MMPs)
- Altered expression of chemokines (IL8)
- Altered growth factor expression (FGFs)
What is metastasis?
Process by which cancer cells spread to other parts of the body
Name 3 routes of metastasis
- Lymphatic
- Haematogenous
- Transcoelomic
What tumours tend to metastasise in a haematogenous fashion?
Sacromas
What tumours tend to metastasise in a transcoelomic fashion?
Ovarian tumours can spread transperitoneally to liver
Describe the multi step process of metastasis
- Primary tumour proliferation
- Invasion of neovasculature
- Embolism and transport
- Adherence to vessel wall
- Extravasation
- Establishment of a microenvironment
- Metastasis
Name 4 common sites of metastasis for breast cancer
- Bone
- Brain
- Liver
- Lung
Name 3 common sites of metastasis for colorectal cancer
- Liver
- Lung
- Peritoneum
Name 5 common sites of metastasis for lung cancer
- Adrenal gland
- Bone
- Brain
- Liver
- Other lung
Name 4 common sites of metastasis for prostate cancer
- Adrenal gland
- Bone
- Liver
- Lung
Describe normal replicative senescence
- Cells have finite lifespan and limited ability to replicate
- Due to telomere shortening
Describe how cancerous cells enable replicative immortality
- Inactivation of pRb / p53 extends lifespan 30 doublings
- Rare mutations lead to immortalization
- Activation of telomerase
Describe induction of angiogenesis by cancerous cells
- Pro-angiogenic factors activated in tumours
- Signal endothelial cell proliferation
- Growth of blood vessels
Name 3 pro angiogenic factors
- VEGF
- FGF1
- FGF2
What is apoptosis?
Programmed cell death
Name 2 pro survival factors activated in tumours
- Bcl-2
2. Cflip
Name 5 causes of cancer
- Lifestyle (tobacco / alcohol / diet)
- Infections
- Radiation exposure
- Age
- Genetics
Name 4 molecular mechanisms driving carcinogenesis
- Mutations
- Chromosomal abnormalities
- Gene amplifications
- Altered gene expression
Name 3 types of point mutations
- Silent
- Nonsense
- Missense
What is a point mutation?
Single change in a base
What is a silent point mutation?
Single change in the base but the protein is unchanged
What is a nonsense mutation?
Single change in the base where there is no coded protein for the new sequence
What is a missense mutation?
Single change in the base where the protein produced is different
Describe 2 examples of point mutations
- Ras family (codes a small GTPase involved in transmitting signals)
- KIT gene (codes a transmembrane tyrosine kinase)
Name 2 ways deletions can occur
- Loss of single base
2. Loss of large regions of chromosome
Describe 2 ways translocation can affect the body
- Production of novel fusion proteins (Bcr-Abl)
2. Juxtaposition to strong promoter upstream (cMyc)
Describe the Philadelphia chromosome
- Chronic Myeloid Leukaemia is characterised by Philadelphia chromosome
- Translocation of portion of q arm of chromosome 22 to q arm of chromosome 9
- Creates fusion gene juxtapositioning the Abl1 gene on chromosome 9 to part of BCR gene on chromosome 22
What is gene amplification?
Increased copy number of genes which may be amplified multiple times (HER2 in breast cancer)
Name 2 epigenetic changes which alter gene expression
- DNA methylation
2. Histone modification
Describe an example of DNA methylation leading to altered gene expression
- p16 methylation
- Acetylation opens up chromatin
- Methylation of chromatin can cause transcriptional activation or repression
Name 4 emerging hall marks of cancer
- Avoiding immune destruction
- Tumour promoting inflammation
- Genome instability and mutation
- Deregulating cellular energetics
Name 3 “E’s” of immunoediting
- Elimination
- Escape
- Equilibrium
