outline of disease processes in cancer Flashcards
most cancers are
monoclonal; arise form single cell
cancers invade
adjacent tissue and are spread by lymphatics nad blood vessels to other parts of the body
cancer cell features
- loss of contact inhibition
- increase in growth factor secretion
- increase in oncogene expression
- loss of tumour suppressor genes
normal cell features
- oncogene expression is rare
- intermittent or co-ordinated growth factor secretion
- presense of tumour suppressor genes
things that initiate cancers are
chemical
physical
iral
things that promote cancers are
growth factors
oncogenes
things that allow progression of cancers
metastasis
aniline dyes can cause
bladdar cancer
- chemical carcenogenesis
nitrogen mustard can cause
leukaemia
- chemical carcenogenesis
aflatoxin can cause
liver damage
physical carcinogens
- ionising radiation
- dose response relationship
- radon source is mainly buildings
- ventillation reduces risk - mechanism
- chromosome translocation
- gene amplification
- oncogene activation
oncogenes function
transforming genes
- positive regulators of growth
- represent gain in function to transformed cells
growth factors function
polypeptide molecules
- regulate cell growth and function
- bind to cell membrane receptors
- stimulate activation of intracellular signal transduction pathways
oncogene stimulation may be
- autocrine
- paracrine
autocrine stimulus is when
- cell carries receptor and secretes growth factor
- cell escapes normal control mechanism
paracrine stimulus is when
- growth factors acting on cell are produced locally the cell or its intermediate neighbours
P53 normal function
tumour suppressor gene
- normal function is as transcriptional regulator
- promotes DNA repair, apoptosis, differentiation
p53 is induced by
DNA damage and hypoxia.
- G1/S checkpoint control gene
metastasis features
- non random
- cascade of limited sequental steps
- involves tumour-host interactions
- survival of the fittest pertains
invasion and metastasis
- tumour invades through basement membrane
- moves into extracellular matrix/connective tissue/surrounding cells
- invades blood vessels
- tumour cells arrested in distant organ
enzymes involved in invasion and metastasis:
In ECM
- Matrix metalloproteinases (MMPs) – several subclasses eg gelatinases
- Plasmin
- Cathepsin
enzymes involved in invasion and metastasis:
cell adhesion
- Cahedrins (loss correlates with tumour invasion and metastasis)
- Integrins
- CD44
angiogenesis is
the formation of new blood vessels.
- key factor in maintenance and progression of malignant tumours
- is a must for tumours that want to grow past 2mm in diameter
degradation of the extracellular matrix is necessary for
new blood vessel formation to occur
intravasation is when
primary tumour enters blood vessel
extravasation is when
primary tumour leaves vessel to metastasise
Anti-VEGF antibody Avastin binds VEGF and prevents
- interaction with receptors
- activation of downstream signalling pathways
most lethal gynecological malignancy
ovarian cancer
Anti-VEGF therapy normalises
vasculature
Why does our immune system not recognise ‘foreign’ cancer cells
- Cancer cells can ‘hide’ from T cells
- PD1 (programmed death receptor) present on T lymphocytes
- Ligand (PDL-1) on tumour cells
- Interaction of these suppresses T cell action
PDL1 is expressed on
cancer cells and precentage of it can give basis for treatment
High levels of PD1 or PDL1 protein expression (IHC) may inhibit
Immune response
Nivolumab – The First
PD-1 Inhibitor Proven to Significantly Improve Overall Survival vs. Docetaxel1 in NSCLC second line therapy (2015)
