Introduction to Cancer Biology Richard Begent

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

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 Chemical Physical Viral Genetic instability Limiting damage DNA repair Anticarcinogens Minimising exposure to carcinogens

The development of a cancer

Immortalisation

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 divisions Senescence DNA Repeated cell division

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

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

Large tumour masses

Metastasis

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 & text The web sites on the questionnaire Cancer Biology by RJB King Pubmed & 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?

The elements of cancer; how do they fit together?

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.