Genes and CancerGenes and Cancer

Prof. Arnaldo FerreiraProf. Arnaldo Ferreira

Impacts, Issues: Between You and Eternity

Cancer strikes one in three people in the United States• Kills one in four

Overall more males than females get cancer• Pattern varies depending upon the type of cancer

Gene mutations and cancer• BRCA1 and BRCA2: “breast cancer susceptibility

genes”

The Characteristics of Cancer

As genes switch on and off, they determine when and how fast the cell will grow and divide, when it will stop dividing, and even when it will die

Cancer can result when controls over cell division are lost

Some Tumors Are Cancer, Others Are Not

Hyperplasmia Cells in a tissue overgrow Resulting defined mass: tumor (neoplasm)• Benign, e.g., moles • Slow growth• Expands in the same tissue; does not spread• Cells look nearly normal

• Malignant • Rapid growth• Invades surrounding tissue and metastasizes• Cell differentiation usually poor

Dysplasia Abnormal change in the size, shape, and

organization of cells in a tissue Often an early step toward cancer• Microscopic characteristics of cancer cells• Behave differently from normal cells

Some Tumors Are Cancer, Others Are Not

Cancer Cells Are Abnormal in Their Growth and Appearance

Normal Moles Are Common Examples of Benign Growths

Main Features of Benign and Malignant Tumors

A Cancer Cell’s Structure Is Abnormal

Cancer is a result of a series of mutations in the cell’s genes • Larger cell nucleus and less cytoplasm• Loss of structural specialization• Cytoskeleton shrinks• Plasma membrane proteins could be lost or

altered• New plasma membrane proteins may appear• Changes passed on to cell’s descendants

Cancer Cells Also Do Not Divide Normally

Cancer cells don’t necessarily divide faster than normal cells; more cancer cells are dividing than dying

Cancer cells do not respond to crowding; loss of contact inhibition• Leads to a disorganized mass; cells may have

extensions• May produce HCG and angiogenin• Metastasis: makes a cancer malignant

Threadlike “False Feet” Are a Common Feature of Cancerous Cells

Cancer Spreads Step-by-Step

Cancer is a Genetic Disease

Cancer is a genetic disease that develops in a predictable sequence of steps

Carcinogenesis• Transformation of a normal cell into a cancerous

cell• Step-by-step transformation

Carcinogenesis Occurs in Predictable Steps

A Common Type of Colorectal Cancer May Develop by These Steps

Colon cancer results from genetic alterations in multiple genes

Inherited mutations in the APC gene dramatically increase risk of colon cancer

Cancer Usually Involves Several Genes

Proto-oncogenes• In normal cells• Code for proteins involved in the stimulus of cell

division

• If altered, may form oncogenes• Alone, do not cause malignant cancer• Require other mutations, including one in a tumor

suppressor gene

Tumor suppressor genes• Stop cell growth and division; prevent cancer

formation• May prevent expression of oncogenes• Retinoblastoma: only one functional copy of a

tumor suppressor gene on chromosome 13• BRCA1 and BRCA2• p53: codes for a regulatory protein that turns off

cell division when the cell is stressed or damaged• If mutated, runaway cell division• More than half of cancers has a mutated or

missing p53 gene

Cancer Usually Involves Several Genes

Types of cancer genes

Types of proteinsTypes of proteinsMutated functionMutated functionNormal functionNormal functionType of geneType of gene

Enzymes for mismatch or excision repair

Fail to repair DNA mutations

Repair DNA mutations

DNA repair gene mutation

Checkpoint molecules

Fails to suppress division

Suppresses cell division

Tumor suppressor gene

Growth factorsPromotes division - abnormal time or cell type

Promotes divisionOncogene

Other Factors Also May Lead to Cancer

Inherited susceptibility to cancer• ~5% of cancers

Viruses• Viral DNA may be inserted into a host cell’s DNA • May switch on a proto-oncogene• May carry oncogenes

Other Factors Also May Lead to Cancer

Chemical carcinogens• Carcinogens: cancer-causing substances that

can lead to a mutation in DNA• Asbestos, vinyl chloride, and benzene• Hydrocarbons in cigarette smoke• Aflatoxin: fungal product

Radiation• UV from the sun and tanning lamps• X-rays: medical and dental• Radon, cosmic rays, and gamma radiation

Cruciferous vegetables can lower cancer risk

Other Factors Also May Lead to Cancer

Breakdowns in immunity• Healthy immune system can target and destroy

cancer cells• When cancer cells have altered proteins at its

surface, cells are not destroyed• Risk of cancer increases: • With age• When an immune system has been suppressed for

a long time• HIV infection• Immunosuppressant drugs• Anxiety and depression

Focus on Environment: Cancer Risk from Environmental Chemicals

Exposure to pesticides• Agricultural chemicals in food and airborne

chemicals due to spraying programs• Reduce exposure; how?

Industrial chemicals

Ames test• Assess chemical’s ability to cause mutations

Some Industrial Chemicals Linked to Cancer

Some Major Types of Cancer

In general, a cancer is named according to the type of tissue in which it first forms

Sarcomas: cancer of connective tissue

Carcinomas: cancer arising from epithelium

Lymphomas: cancer of lymphoid tissue

Leukemias: cancer of stem cells

Gliomas: cancer of brain glial cells

Cancer Is Named for the Site in the Body Where It First Develops

In the U.S., More than 1 Million People Are Diagnosed with Cancer Each Year

Cancer Screening and Diagnosis

Early and accurate diagnosis of cancer is important to maximize the chances that a cancer can be cured

Blood Tests Can Detect Chemical Indications of Cancer

Tumor markers• Produced by particular types of cancer cells• Produced by certain cells in response to cancer• Detected by blood tests • HCG• PSA: prostate-specific antigen

Medical Imaging Can Reveal the Site and Size of Tumors

Medical imaging• MRI (magnetic resonance imaging):

reveals tumors obscured by bone• X-rays• Ultrasound• CT (computerized tomography)

Medical Imaging Can Reveal the Site and Size of Tumors

Radioactive tracers• Tracked using a PET scanner• Diagnosis of thyroid cancer using radioactive

iodine

Radioactively labeled monoclonal antibodies• Useful in the location and size of certain tumors in

the colon, brain, and bone

DNA probe: locates mutated genes, e.g., p53

Radioactive Tracers Also Can Reveal Cancer Tumors

Biopsy Is the Only Sure Way to Diagnose Cancer

Biopsy• Removal and microscopic examination of tissue

Seven common cancer signs: CAUTION

Light Microscope Image Shows Cancerous Cells in Breast Tissue

Cancer Treatment and Prevention

When a person is diagnosed with cancer, a variety of weapons are available to combat it

Chemotherapy drugs

Radiation therapy

Surgery

Chemotherapy and Radiation Kill Cancer Cells

Chemotherapy• Drugs used to kill cancer cells; disrupt some

aspect of cell division• Toxic to healthy cells; hair, bone marrow,

lymphocytes, and epithelial cells of intestinal lining • Side effects include hair loss, nausea, vomiting,

and reduced immune responses• Genetic approach to chemo in the future

Chemotherapy and Radiation Kill Cancer Cells

Radiation therapy• Used when cancer is small or has

not spread• Radioisotopes used, e.g., Ra-226

and Co-60

Chemotherapy and radiation destroy healthy cells

More precise treatments• Monoclonal antibody treatment• Interferon treatment; limited at

present

Good Lifestyle Choices Can Limit Cancer Risk

Avoid tobacco completely

Maintain a desirable weight; eat a low-fat diet with plenty of fruits and vegetables

Drink alcohol in moderation

Make sure your living and work environment is safe from carcinogens

Protect your skin from the sun’s UV rays

This Cancer Cell Is Surrounded by White Blood Cells

Cancer Causes and Contributing Factors

Types of Cancer

• Skin Cancer

• Colon Cancer

• Prostate Cancer

• Lung Cancer

• Liver Cancer

• Brest Cancer

• Bladder Cancer