1. Introduction to Cancer Biology Richard Begent

2. Aim To explain the principles of the development of cancer and its effect on patients

3. 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

4. Cancer is caused by multistep gene damage in a single cell Origins of damage Inherited Replication errors Carcinogens Chemical Physical Viral Genetic instability Limiting damage DNA repair Anticarcinogens Minimising exposure to carcinogens

6. The development of a cancer

10. Immortalisation

11. TTAGGG x n 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

12. TTAGGG x n Telomerase maintains telomere length Cells can replicate indefinitely Cancer cells, foetal cells & germ cells

16. Altered proteins Altered function of mutant proteins Splice variants Altered post-translational modification

18. Carcinoma Normal colon Tumour invading through muscle wall of bowel Normal muscle wall of bowel Invasion

22. Large tumour masses

24. Metastasis

26. 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

28. 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

32. Tasks for this morning Answer questionnaires using What you have learnt in the lecture & text The web sites on the questionnaire Cancer Biology by RJB King Pubmed & other reading

33. 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

34. The elements of cancer; how do they fit together?

35. Tasks for this week Work on the questionnaires and bring them completed and with your questions for discussion at 4pm on Friday 28 th April Work in groups of 3-6 to prepare a scheme linking the elements of cancer in way that explains the process of cancer from origin to death or cure.