Retroviral oncogenes

Cellular protooncogenes

Mutation carrying cells with proliferation advantage Activated protooncogene

The p53 gene product protects from propagation of cells that carry damaged DNA

Series of mutations on tumor suppressor genes, repair genes and oncogenes

Metastasis Spread of malignant cells from the primary site of cancer to any other part of the body Main cause of therapy failure Advanced disease stage but also at early stages Secondary sites depend on primary tumor

Blood (and lymphatic) vessels are the highways for metastatic cancer cells

IARC categories of substances regarding carcinogenicity 1. Sufficient evidence of carcinogenicity in humans 2a. Probably a human carcinogen 2b. Possibly a human carcinogen 3. Inadequate evidence of carcinogenicity in humans 4. Not carcinogenic

US - Natl. Toxicology Program categories of carcinogens Part A –Known to be human carcinogens –~40 chemicals or chemical mixtures Part B –Reasonably anticipated to be human carcinogens –>100 chemicals