introduction to cancer biology richard begent. aim to explain the principles of the development of...
TRANSCRIPT
Objectives
By the end of the session students should
be able to:
• List the elements of the process of development of cancer
• Link the elements in a structured description of the process of cancer
• Relate these principles to selected clinical examples
Cancer is caused by multistep gene damage in a single cell
Origins of damage•Inherited •Replication errors•Carcinogens
ChemicalPhysicalViral
•Genetic instability
Limiting damage •DNA repair•Anticarcinogens•Minimising exposure to
carcinogens
TTAGGG x n
TTAGGG x n
TTAGGG x n/2
TTAGGG x n/2
Telomeres (TTAGGG repeats) shorten with each cell division in normal adult cells. Most cells become senescent and die after 30-60 divisions
Senescence
DNA
Repeated cell division
TTAGGG x n
TTAGGG x n
Telomerase maintains telomere length
Cells can replicate indefinitely
Cancer cells, foetal cells & germ cells
Altered proteins
• Altered function of mutant proteins• Splice variants • Altered post-translational
modification
New blood vessels develop in response to the tumourpermitting it to grow to produce sizeable masses
New bloodvessels
Carcinoma
Normal colon
Tumour invading through muscle wall of bowel
Normal muscle wall of bowel
Invasion
Loss of homeostasis
• Replacement of vital organs by tumour• Infiltration into organs• Pressure from tumour masses• Breaching natural barriers to infection• Paraneoplastic syndromes• Effects of treatment• Psychological effects of debilitating
illness
Principles of management
• Avoid risk • Identify and screen groups at risk• Diagnose at the earliest possible stage• Establish extent of spread• Establish prognosis• Local treatment for localised disease• Systemic treatment for systemic disease• Combinations are sometimes appropriate• Monitor response and adjust treatment• Monitor homeostasis and adapt
management
Tasks for this morning
• Answer questionnaires using What you have learnt in the lecture &
textThe web sites on the questionnaireCancer Biology by RJB KingPubmed & other reading
Look up
• Search for lung cancer• Name 2 genes of known function, which are mutated in this disease• Are they tumour suppressors or oncogenes or do they have another function?
http://www.ncbi.nlm.nih.gov/Omim/getmorbid.cgi
InheritanceEnvironment
VirusesAge
Multistep gene damage
DNA repairLimitation of exposureAnti-carcinogens
Loss of tumour suppressor gene functionGain of oncogene function
Uncontrolled proliferation
Immortalisation
Genetic Instability
Invasion
Metastasis
Generation of tumour vasculature
Formation of large tumour masses
Loss of homeostasisDeath
Cure
Treatment
Resistance to apoptosis
Single cancer cell
The elements of cancer; how do they fit together?