What is cancer?

Abnormal cell growth (neoplasia ± New growth) Malignant as opposed to benign
Benign: slow growth, non-invasive, no metastasis Malignant: rapid growth, invasive, potential for metastasis

Benign or malignant?
‡ Benign tumours do not spread from their site of origin, but can crowd out (squash) surrounding cells eg brain tumour, warts. ‡ Malignant tumours can spread from the original site and cause secondary tumours. This is called metastasis. They interfere with neighbouring cells and can block blood vessels, the gut,. ‡ Both types of tumour can tire the body out as they both need a huge amount of nutrients to sustain the rapid growth and division of the cells.

are not familial ‡ Cancer is a genetic disease. but the majority of mutations that lead to cancer are somatic .Is cancer a heritable disease? ‡ There are heritable cancer syndromes ‡ The majority of cancers. however.

abl. Rb. NF1 ‡ MicroRNA ± Transcriptome control . MEN1.Cancer pathogenesis ‡ Oncogenes ± myc. src. ras. bcl2 ‡ Tumor suppressor genes ± p53. APC.

The path to cancer ‡ ‡ ‡ ‡ Clonal proliferation Starts from a single cell Expansion in steps Pre-malignant states ± Polyp. MDS. MGUS ‡ Serial accumulation of mutations ± Clonal evolution ± Resistance .

2000 .Hallmarks of cancer ‡ ‡ ‡ ‡ ‡ ‡ ‡ Self-sufficiency in growth signals Insensitivity to anti-growth signals Evading apoptosis Limitless reproductive potential Sustained angiogenesis Tissue invasion and metastases Genomic instability Hanahan & Weinberg. 2000 Hanahan & Weinberg.

Tissue and tumor architecture .

Cancer stem cells ‡ ‡ ‡ ‡ ‡ ‡ Present in most (all) tumors Small fraction of population No universal marker Often resistant to therapy May be important target of therapy Cancer initiating cells in mice .

pylori --> gastric cancer Chemicals --> B[a]P --> lung cancer UV and ionizing radiation --> skin cancer ‡ What do these agents have in common? .What causes the mutations that lead to cancer? ‡ ‡ ‡ ‡ Viruses: HPV --> cervical cancer Bacteria: H.

Mutagens Viruses: insertional mutagenesis .

Chemicals: DNA adducts UV and ionizing radiation: single and double strand DNA breaks .

Carcinogens ‡ Ionising radiation X Rays. Remember you can t inherit cancer its just that you maybe more susceptible to getting it . UV light ‡ Chemicals tar from cigarettes ‡ Virus infection papilloma virus can be responsible for cervical cancer. ‡ Hereditary predisposition Some families are more susceptible to getting certain cancers.

a tumour would be unable to continue growing. however. now the size of a small grape. the growth of the tumour accelerates. angiogenesis takes place.Angiogenesis Often during the development of earlier stages of the tumour. With the new blood supply. Without blood and the nutrients it carries. is large enough to be detected as a lump . Angiogenesis is the recruitment of blood vessels from the network of neighbouring vessels.

Tumour cells travel . .metastasis Metastasis is now underway. Most of these cells will die soon after entering the blood or lymph circulation. as tumour cells from the original cancer growth travel throughout the body.

cell death .g. gene transcription e.Ras Genes that have the ability to cause cells to become cancerous. cell cycle control. Oncogenes are derived from normal cellular genes that have either become mutated or are overexpressed.What types of genes get mutated in cancer? ‡ Oncogenes are activated ± Normal function: cell growth. ‡ Tumor suppressor genes are inactivated ± Normal function: DNA repair.

p53 a classic tumor suppressor ‡ ‡ ‡ ‡ The guardian of the genome Senses genomic damage Halts the cell cycle and initiates DNA repair If the DNA is irreparable. p53 will initiate the cell death proc .

Rb is a crucial cell cycle checkpoint .Rb a classic tumor suppressor ‡ ‡ ‡ ‡ Rb binds to a protein called E2F1 E2F1 initiates the G1/S cell cycle transition When bound to Rb. E2F1 can't function Thus.

chromosome segregation) ‡ Mutations in tumor suppressor genes lead to the mutator phenotype mutation rates increase ‡ Often the 1st mutation in a developing cancer .Tumor suppressors ‡ Guardian(s) of the genome ‡ Often involved in maintaining genomic integrity (DNA repair.

Types of proteins encodes by oncogenes .

Mechanisms of oncogene activation .

Ras Protein ASSOCIATION WITH HUMAN CANCERS Ras Protein Activated by mutations in 20 to 30 percent of cancers THERAPEUTIC APPROACHES Inhibit Ras maturation .

What can cancer therapies target? ‡ Classic cancer therapies target rapidly dividing cells ‡ Target the DNA ± Ionizing radiation ± Chemotherapy ‡ Many side effects ± Hair loss ± Weakened immune system ± Problems with GI tract .

there are few side effects since these therapies are specifically targeted to cancer cells . targeted therapies attack specific proteins that are abnormally expressed in a tumor ‡ May block over-expressed growth factor receptors --> Herceptin ‡ Generally.What can cancer therapies target? ‡ A person's immune system will not target tumor cells because they appear to be self ‡ Some new therapies focus on activating one's immune system against a cancer ‡ Modern.

Discussion questions ‡ What is the difference between monoclonal and polyclonal? ‡ Why would a microscope be a good tool for detecting and diagnosing cancer? ‡ Cancer is a genetic disease. so why does environment matter? ‡ What s the difference between a carcinogen and a mutagen .

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