Outline of Disease Process CANCER Flashcards
What does “cancers are mostly monoclonal” mean?
They mainly arise from one cell
Whats different about cancer cells?
Increased growth factor secretion
Increased in oncogene expression
Loss of tumour supressor genes
Loss of contact inhibition
What are the 5 steps of carcinogenesis?
Carcinogen Initiation Promotion Tumour Growth Progression
What is a diagnostic threshhold?
The size at which a cancer becomes clinically detectable
What are the 3 types of carcinogens?
Chemical
Physical
Viral
What chemical carcinogen causes liver cancer?
Aflatoxin (in mouldy peanuts)
Most common chemical carcinogens?
Smoking & alcohol
Physical carcinogen?
Ionising radiation
How does ionising radiation cause cancer?
Ionising radiation:
- Translocate chromosomes
- Amplify certain Genes
- Activate Oncogenes
What viral carcinogen causes burkitts lymphoma?
Herpes virus causes burkitts lymphoma
What viral carcinogen caues liver cancer?
HEP B can cause liver cancer.
What 3 things are involved in the promotion stage?
Oncogens
Tumour supresser genes
Growth factors
How do oncogenes promote the progression stage?
Oncogenes are positive regulaters of growth, they stimulate tumour growth
How do growth factors stimulate cell growth?
Bind to cell-membrane receptors & activate intracellular signal transduction pathways
Define autocrine signaling?
When a cell secretes a substance (i.e. growth factor) that acts on receptors on the same cell inducin changes in it
Whats the difference between autocrine & paracrine signalling?
Paracrine signalling involves signals acting on nearby cells, autocrine involves signals acting on the same cell that produces them
Whats the normal function of tumor suppressor genes?
Promoting DNA repair, Apoptosis & differentiation
What normally induces tumor suppressor genes to act?
Hypoxia & DNA damage
Name a tumor supressor gene
P53
How does progression (metastasis) occur?
Tumour invades through basement membrane.
Invades into ECM/connective tissue/other cells
Invades blood vessles
Finally cells arressted in a distant tissue
IS the progression stage random?
No its a series of limited sequential steps involivng host-tumor interactions
At what point is angiogenesis vital for continued tumor growth?
New vessels must form for a tumour to grow beyond 2mm in diameter
How does angiogenesis affect the ECM?
Enzymes degrade the ECM to allow for new vessel growth
How is angiogenesis related to cancer severity?
Theres a correlation between vessel density and tumour malignancy/metastasis.
How is angiogenesis inhibited?
- > Avastin (anti-VEGF antibody) binds to VEGF
- > prevents VEGF-receptor interaction
What is the ultimate effect of anti-VEGF treatments?
Vascular regression & dormant tumours
What is the purpose of T cell inhibition receptors?
TO maintain self-tolerance & protect tissue duing immune responses
How do tumours blind T cells to them?
They express a specific ligand and bind to T cell inhibition receptors
What ligand/receptor combo is used by cancers to blind T cells?
ligand on cancer cell = PDL-1
Receptor on T cell = PD1
Explain therapeutic options to bypass T cell blindness to cancer cells?
Block PDL-1 on cancer cell or PD1 on T cell.
Or use modified aritifical T cells (chimeric antigen receptors, CAR T cells)
