3.1.3.A Understanding Cancer What is Cancer

Understanding Cancer and Related Topics What Is Cancer? National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Different Kinds of Cancer Understanding Cancer and Related Topics National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Leukemias: Bloodstream Some common carcinomas: Lung Breast (women) Colon Bladder Prostate (men) Lymphomas: Lymph nodes Some common sarcomas: Fat Bone Muscle NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Cancer is Complex

Understanding Cancer and Related Topics Naming Cancers National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer 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 NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Loss of Normal Growth Control National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Normal cell division Cell Suicide or Apoptosis Cell damage— no repair Cancer cell division First mutation Second mutation Third mutation Fourth or later mutation Uncontrolled growth NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Example of Normal Growth Understanding Cancer and Related Topics National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Dead cells shed from outer surface Epidermis Cell migration Dividing cells in basal layer Cell Division Dermis Balance between cell death and cell production NCI Web site: http://cancer.gov/cancertopics/understandingcancer

The Beginning of Cancerous Growth National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer 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 NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Understanding Cancer and Related Topics Tumors (Neoplasms) National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Neoplasm (new formation/creation) Increased rate of cell division Decreased (or no) apoptosis to compensate Underlying tissue NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Invasion and Metastasis Understanding Cancer and Related Topics National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer 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 NCI Web site: http://cancer.gov/cancertopics/understandingcancer

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 Understanding Cancer and Related Topics National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites Time NCI Web site: http://cancer.gov/cancertopics/understandingcancer

By definition the term “cancer” applies only to malignant tumors

Why Cancer Is Potentially Dangerous National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Brain 2 Cancer cells in the liver would be called metastatic melanoma, not liver cancer. Melanoma cells travel through bloodstream 3 Liver Melanoma (initial tumor) 1 NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Understanding Cancer and Related Topics Genes and Cancer National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Viruses Chemicals Radiation Heredity Chromosomes are DNA molecules NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Understanding Cancer and Related Topics DNA Structure National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Chemical bases A T C G DNA molecule NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Understanding Cancer and Related Topics DNA Mutation National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer C A A G C T A A C T DNA Normal gene C A A G C G A A C T Single base change C A A G G C G C T A A C T Additions C T C A A G A A C T Deletions NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Understanding Cancer and Related Topics Oncogenes National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Normal cell Normal genes regulate cell growth Oncogenes accelerate cell growth and division Cancer cell Mutated/damaged oncogene NCI Web site: http://cancer.gov/cancertopics/understandingcancer

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 National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer 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 DNA Cell nucleus Cell proliferation Normal Growth-Control Pathway NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Oncogenes are Mutant Forms of Proto-Oncogenes National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer 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 NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Tumor Suppressor Genes National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Normal cell Normal genes prevent cancer Remove or inactivate tumor suppressor genes Cancer cell Damage to both genes leads to cancer Mutated/inactivated tumor suppressor genes NCI Web site: http://cancer.gov/cancertopics/understandingcancer

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 National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Restrains cell growth and division Tumor Suppressor Gene Proteins Growth factor Receptor Signaling enzymes Transcription factors DNA Cell nucleus Cell proliferation NCI Web site: http://cancer.gov/cancertopics/understandingcancer

p53 Tumor Suppressor Protein Understanding Cancer and Related Topics Triggers Cell Suicide National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer p53 protein Normal cell Excessive DNA damage (repair not possible) Cell suicide (Apoptosis) NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Understanding Cancer and Related Topics DNA Repair Genes National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Normal DNA repair T C G A C Base pair mismatch No cancer T C T A C A G C T G T C T A C T C T A C A G C T G Cancer A G T G A G A T G No DNA repair NCI Web site: http://cancer.gov/cancertopics/understandingcancer

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 National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer 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 inactivates suppressor gene Cells proliferate Mutations inactivate DNA repair genes Proto-oncogenes mutate to oncogenes More mutations, more genetic instability, metastatic disease NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Understanding Cancer and Related Topics Genes Implicated in Cancer Mutations and Cancer National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Genes Implicated in Cancer NCI Web site: http://cancer.gov/cancertopics/understandingcancer

Cancer Tends to Corrupt Surrounding Environment National Cancer Institute Understanding Cancer and Related Topics Understanding Cancer Growth factors = proliferation Invasive Matrix Proteases Fibroblasts, adipocytes Cytokines Blood vessel Cytokines, proteases = migration & invasion NCI Web site: http://cancer.gov/cancertopics/understandingcancer