Outline of Disease Processes in Cancer Flashcards
How would you describe the development of cancer?
Multistage carcinogenesis.
Carcinogen -> Initiaion -> Promotion -> Tumour growth -> Progression
What gives rise to new therapeutic options?
Better understanding of molecular biology
What is increasing relevant for the therapy available for cancer?
Immnotherapy/ biological therapy
What factors cause initiation of cancer?
Chemical, physical, viral
What factors cause promotion of cancer?
Growth factors, oncogenes
What factors cause progression?
Metastasis
Cancer cells vs normal cells
CANCER:
- frequent mitoses
- loss of contact inhibiton
- increase in secretion of growth factors
- increase in oncogene expression
- loss of tumour suppressor genes
NORMAL:
- few mitoses
- uniform arrangement
- co-ordinated growth factor secretion
- rare oncogene expression
- presence of tumour suppressor genes
What causes initiation- Chemical.
In more detail?
Chemical i.e.
- Analine dyes
- Aflatoxin
- Mustard gas
- Alcohol and smoking
What causes initiation- Physical.
in more detail?
Ionising radiation:
- Radon source is mainly buildings
- risk increased by smoking
What is a carcinogen?
a substance capable of causing cancer in living tissue.
What causes promotion- Oncogenes.
In more detail- what are they and what do they do?
- Pro cancer genes
- Represent a gain in function to transformed cells
What causes promotion- Growth factors.
In more detail- what are they, what do they do?
- Polypeptide molecules
- Regulate cell growth and regulation
- Bind to cell membrane receptors and stimulate intracellular single transduction pathways
What causes initiation- physical.
In more detail? (2)
Viral carcinogens:
-Herpes virus
-Papillomavirus
Hep B
What are properties of metastasis?
- Not random
- Cascade of limited sequential steps
How does metastasis occur?
- Tumour invades through basement membrane
- Moves into extracellular matrix/ connective tissue/surrounding cells
- Invades blood vessels
- Tumour cells “arrested” in distant organ
What molecules are involved when tumour invades through basement membrane, and move into Extracellular matrix?
-Many enzymes involved i.e. Matrix metalloproteinases (MMPs), Plasmin, Cathepsin
What are the two types of stimulation?
Autocrine and Panacrine
What is autocrine stimulation?
- Cell carries receptors and secretes growth factor
- Cell escapes normal control mechanism
What is paracrine stimulation?
Growth factors on a cell are produced locally by the cell or its immediate neighbours
What is the most commonly altered gene in human tumours?
p53
What is Angiogenesis and what does it involve?
- Formation of new blood vessels
- involves degradation of the EM
Why is angiogenesis relevant to tumour formation?
- is a key factor in the maintenance and progression of malignant tumours
- New blood vessel formation must form in order for a tumour mass to exceed 2mm in diameter
What does cancer therapy involve?
Drugs to exploit our knowledge on specific growth factors on how it affects tumour growth and regulation.
Example of drugs in cancer therapy?
-Anti-VEGF antibody Avastin binds VEGF on the surface of vascular endothelial cells.
It prevents:
- interaction with receptors
- the activation of downstream signalling pathways, that would normally lead to the growth, proliferation, migration and survival of endothelial cells.
What does Anti-VEGF antibody Avastin bind to VEGF ultimately lead to?
- reduction in microvascular growth,
- inhibits progression of metastatic disease
- reduces intratumoral pressure, which may improve the delivery of cytotoxic agents.
Why does our immune system not recognise foreign cancer cells?
Cancer cells hide from T cells
What is the increasingly relevant immunotherapy do?
Immunotherapy:
- PD1 (programme death receptor) is present on T lymphocytes
- Ligand (PDL-1) is on tumour cells.
- Interaction of these suppresses T cell action
- This is a therapeutic opportunity to block PD1 or PDL-1, as it causes immune damage to tumour
How does PD1 receptor on T lymphocytes work?
- blocks the pathways with specific antibodies called immune checkpoint inhibitors.
- Once the immune system is able to find and respond to the cancer, it can stop or slow cancer growth.
