Introduction to Cancer Biology Richard Begent. Aim To explain the principles of the development of cancer and its effect on patients.

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

ChemicalPhysicalViral

•Genetic instability

Limiting damage •DNA repair•Anticarcinogens•Minimising exposure to

carcinogens

The development of a cancer

An epithelial surface

Lumen

Epithelialcells

Basement membrane

Origin of cancer in a single cell

Uncontrolled proliferation

Immortalisation

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

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 &

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?

Tasks for this week

• Work on the questionnaires and bring them completed and with your questions for discussion at 4pm on Friday 28th 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.