Outline of Cancer Disease Process Flashcards
Define cancer
Carcinoma or disorderly growth of epithelial cells which invade adjacent tissue and spread by the lymphatics and blood vessels to other parts of the body
What type of cells does cancer usually arise from?
Epithelial, only 20% arise from non-epithelial connective tissue, musculoskeletal or nervous tissues
How can you differentiate between normal and cancerous cells using a microscope?
- Lots of blood vessels (increased angiogenesis)
- Cells at different stages of the cell cycle
- Abnormal heterogeneous cells
- Irregular and messy borders
- Irregular nuclei
Describe the three stages of carcinogenesis
o Initiation – irreversible genetic damage to cells that proliferate and survive for the lifetime of the organism
o Promotion – reversible changes that increase chances of it progressing to cancer, including the selective clonal expansion of the initiated cells. This is aided by growth factors and oncogenes
o Progression – irreversible malignant conversion of the initiated prenoeplastic cell into one that expresses the malignant phenotype
How large does a tumour have to be before it is usually detected?
1cm
What can initiate carcinogenesis?
o Chemical carcinogens
o Physical carcinogens
o Viral carcinogens
Describe some chemical carcinogens that can initiate cancer development
Chemical carcinogens:
• Polycyclic hydrocarbons and soot on scrotal cancer
• Anilene dyes and bladder cancer
• Aflatoxin (mouldy peanuts) and liver cancer
• Nitrogen mustard and leukaemia
• Alcohol and smoking
Describe some physical carcinogens
Physical carcinogens:
• Ionising radiation – dose response relationship, affects chromosome translocation, influences gene amplification and activated oncogenes
Describe some viral carcinogens
Viral carcinogens:
• Herpes virus and Burkitts lymphoma
• Human papillomavirus and cervical cancer
• Retroviruses HTLV1 and HTLV2 on leukaemia + lymphoma
• Hepatitis B and liver cancer
What causes cancer promotion?
Mutations in either
- protoonocogenes e.g. Bcl2 activation
- growth factors
- tumour suppressor genes e.g. p53
What is Bcl2?
Bcl2 is a protooncogene, activation prevents apoptosis
What is p53?
Tumour suppressor gene, is the most commonly altered gene in human tumours (37% but higher in lung and colon).
What is the normal function of tumour suppressor genes?
Normal function is as transcriptional regulator; promotes DNA repair, apoptosis, differentiation
What usually causes genetic mutations?
DNA damage and hypoxia
What enzymes allow the spread of cancer into the ECM?
- Matrix metalloproteinases (MMPs)
- Plasmin
- Cathepsin
What cell adhesion molecules are affected during invasion by tumour cells?
- Cadherins
- Integrins
- CD44
What type of imaging is particularly useful when testing for metastases?
PET
How big can a tumour get without the requirement of angiogenesis?
2mm
What is Avastin (bevacizumab)?
- The humanised anti-VEGF MAb Avastin (bevacizumab) prevents the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2 on the surface of vascular endothelial cells.
- This prevents activation of the VEGF receptors and of the downstream signalling pathways that would normally lead to the growth, proliferation, migration and survival of endothelial cells of the blood vessels.
What is PDL1?
- Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that has been speculated to play a major role in suppressing the immune system during particular events such as pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis.
- PDL-1 has now been found to be expressed on some tumour cells
What drug targets PDL1?
atezolizumab
What is atezolizumab?
PDL1 MAb
What is ipilimumab?
Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
What drug targets CTLA4?
Ipilimumab
