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3.1.3.A Understanding Cancer What is Cancer What Is Cancer? Different Kinds of Cancer Some common carcinomas: Lung Leukemias: Bloodstream Lymphomas: Lymph nodes Breast (women) Colon Bladder Prostate (men) Some common sarcomas: Fat Bone Muscle Cancer is Complex Naming Cancers Cancer Prefixes Point to Location Prefix Meaning adeno- gland chondro- cartilage erythro- red blood cell hemangio- blood vessels hepato- liver lipo- fat lympho- lymphocyte melano- pigment cell myelo- bone marrow myo- muscle osteo- bone Loss of Normal Growth Control Normal cell division Cell Suicide or Apoptosis Cell damage— no repair Cancer cell division First mutation Second mutation Third Fourth or mutation later mutation Uncontrolled growth Example of Normal Growth Dead cells shed from outer surface Epidermis Dividing cells in basal layer Cell migration Cell Division Dermis Balance between cell death and cell production The Beginning of Cancerous Growth basal cells now divide faster than is needed to replenish the cells being shed from the surface of the skin. Both daughter cells retain capacity to divide. Underlying tissue Tumors (Neoplasms) Neoplasm (new formation/creation) Increased rate of cell division Decreased (or no) apoptosis to compensate Underlying tissue Invasion and Metastasis Cancers spread using 2 mechanisms: • invasion • metastasis 1 Cancer cells invade surrounding tissues and blood vessels 2 Cancer cells are transported by the circulatory system to distant sites 3 Cancer cells reinvade and grow at new location Invasion and Metastasis Invasion - direct migration and penetration by cancer cells into neighboring tissues. Metastasis - ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through the bloodstream, and then invade normal tissues elsewhere in the body. VIDEO Malignant versus Benign Tumors Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis Time Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites By definition the term “cancer” applies only to malignant tumors Why Cancer Is Potentially Dangerous Brain 2 Cancer cells in the liver would be called metastatic melanoma, not liver cancer. 3 1 Liver Melanoma (initial tumor) Melanoma cells travel through bloodstream Genes and Cancer Viruses Chemicals Radiation Heredity Chromosomes are DNA molecules DNA Structure Chemical bases A C DNA molecule T G DNA Mutation DNA CA AG C T A A C T Normal gene CA AG C G A A C T Single base change CA A G G CG C T A A C T Additions C T CA A G A A C T Deletions Oncogenes Normal cell Cancer cell Mutated/damaged oncogene Normal genes regulate cell growth Oncogenes accelerate cell growth and division Oncogenes An oncogene is a gene that has the potential to cause cancer. Categories: Growth factors - Induces cell proliferation Receptor tyrosine kinases – Cell signaling Cytoplasmic tyrosine kinases – Cell signaling Cytoplasmic Serine/threonine kinases – Cell signaling Regulatory GTPases – Cell signaling Transcription factors – Regulates gene transcription In tumor cells oncogenes are often mutated or expressed at high levels. Oncogenes Most normal cells undergo apoptosis Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer 1970 – First oncogene identified (dozens identified since) Many cancer drugs target proteins encoded by oncogenes. Proto-Oncogenes and Normal Cell Growth A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression Growth factor Receptor Signaling enzymes Transcription factors Cell nucleus DNA Cell proliferation Normal Growth-Control Pathway Oncogenes are Mutant Forms of Proto-Oncogenes Inactive growth factor receptor Inactive intracellular signaling protein Signaling protein from active oncogene Activated gene regulatory protein Transcription Cell proliferation driven by internal oncogene signaling Tumor Suppressor Genes Normal genes prevent cancer Normal cell Remove or inactivate tumor suppressor genes Cancer cell Damage to both genes leads to cancer Mutated/inactivated tumor suppressor genes Tumor Suppressor Genes Individuals who inherit an increased risk of developing cancer often are born with one defective copy of a tumor suppressor gene. Because genes come in pairs (one inherited from each parent), an inherited defect in one copy will not lead to cancer because the other normal copy is still functional. But if the second copy undergoes mutation, the person then may develop cancer because there no longer is any functional copy of the gene. Tumor Suppressor Genes Act Like a Brake Pedal Tumor Suppressor Gene Proteins Growth factor Restrains cell growth and division Receptor Signaling enzymes Cell nucleus Transcription factors DNA Cell proliferation p53 Tumor Suppressor Protein Triggers Cell Suicide p53 protein Normal cell Excessive DNA damage (repair not possible) Cell suicide (Apoptosis) DNA Repair Genes Normal DNA repair T C GA C Base pair mismatch No cancer TC T AC AG C T G TC TAC TCT AC AG C T G Cancer AG TG AG A T G No DNA repair DNA Repair Genes Xeroderma pigmentosum • Inherited defect in a DNA repair gene. • Patients cannot effectively repair the DNA damage that normally occurs when skin cells are exposed to sunlight • Exhibit an abnormally high incidence of skin cancer Certain forms of hereditary colon cancer also involve defects in DNA repair. Cancer Tends to Involve Multiple Mutations Benign tumor cells grow only locally and cannot spread by invasion or metastasis Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites Time Mutation Cells inactivates proliferate suppressor gene Mutations inactivate DNA repair genes Proto-oncogenes mutate to oncogenes More mutations, more genetic instability, metastatic disease Mutations and Cancer Genes Implicated in Cancer Cancer Tends to Corrupt Surrounding Environment Growth factors = proliferation Invasive Matrix Proteases Fibroblasts, adipocytes Blood vessel Cytokines, proteases = migration & invasion Cytokines
