Cancer

What Is Cancer

  • Uncontrollable growth of cells

  • 100 different types of cancer

    • Skin, brain, colon, prostate, breast, blood, liver, etc

  • Some are benign

    • One location, doesn't spread

    • Cannot spready by invasion or metastasis

  • Others are malignant

    • Spread to other parts of the body

    • Invade neighboring tissue, enter blood vessel and metastasize to different sites

  • Metastasis

    • Tumour formation

  • 40% of us will be affected by one form of cancer or another in our lifetime


Healthy Cells

Cancer Cells

Large cytoplasm

Small cytoplasm

Single nucleus

Multiple nuclei

Single nucleolus

Multiple and large nucleoli

Fine chromatin

Course chromatin


Cancerous cells

  • Many cells continue to grow and divide

  • Variation in size and shapes of cells

  • Nucleus that is larger and darker than normal

  • Abnormal number of chromosomes arranged in a disorganized fashion

  • Cluster of cells without a boundary


Healthy Cell Growth

  • Cell anchor to dish surface and divide

  • When cells form a complete single layer they stop dividing (density dependent inhibition)

  • If some cells scrape away, they divide to fill the gap and then stop when fill


Cancer cell Growth

  • They do not have density dependent inhibition

  • Continues to grow, what causes the tumour growth as long as it has enough nutrient


Angiogenesis

  • Cancer cells redirect blood vessel growth

  • Redirects blood vessel to provide the tumour with oxygen an nutrients


Metastasise

  • Cancer cells break loose from tumour and spreads


Features of Cancer Cells

  • Do not response to signals that control the cell cycle, they have their own internal signals

  • Can be grown in the lab for up to 25 years. Normal cells die after 1-2 years

  • G1 checkpoint does not stop cancer cells from dividing through mitosis

  • Programmed cell death does not affect cancer cells

  • DNA has abnormalities

  • Higher activities of tyrosine kinases

  • Growth of cancer cells causes a redirection of growth of blood vessels


Causes of Cancer

  • Caused by mutation in segments of DNA that control the production of proteins regulating the cell cycle

  • Carcinogens

    • Substances and agents that are know to cause cancer


Cell Cycle Regulators

  • Cyclin

    • A protein that regulates the timing of the cell cycle

    • Levels are higher in cancer cells

      • More cyclin, more cell division to occur

  • Cancer

    • Uncontrolled cell division of abnormal cells

    • Cells od not enter the G0 (resting) phase


What causes cancer?

  • Everyone has pre-cancerous cells

  • Continual irritation of these pre-cancerous cells triggers the development of cancer

  • More than 80% of cancers are caused by exposure to carcinogens

    • Chemicals

    • Radiation

    • Viruses


How Normal Genes are disrupted

  • Proto-oncogenes (normal function)

  • When exposed to carinogens, Proto-oncogene turns to cancer causing oncogene

  • Cancer tumour cells proliferate


We have tumour suppressors gene that supress tumour growth

  • If a mutation occurs

    • Cells proliferate

    • Mutation inactivates dna repair gene

    • Mutation of proto-oncogene create an oncogene

    • Mutation activates several more tumor suppressor gene

    • Turns to cancer


Triggers of Cancer Cells

  • Mutation in normal tumour-suppressive genes to make them less active

    • P53 gene is found in >50% of all cancers

Mutation to change proto-oncogene to oncogene

  • Continue to cause cell division

Other mutation develop to result in >10

In older people mutation can accumulate over time to a greater extent >50


Genetic Changes and Cancer

  • Heredity

  • UV radiation

  • Chemicals

  • Viruses

  • Smoking

  • Cells dividing


Smoking causes Cancer

  • 5000 different chemicals released

  • Chemicals enter our blood stream and can affect the entire body

  • Chemicals damage our DNA, including the key parts that protect against cancer

  • Other chemicals cause damage by interfering with how cells repair DNA damage

  • DNA damage can cause cancer


Triggers of Cancer Cells

  1. From X-rays, UV irradiation, pesticides, asbestos, formaldehyde, hair dyes, tobacco

    1. Cause damage to DNA that is not repaired in time

  2. Virus infection (oncovirus)

    1. About 15% of all cancers

      1. Hepatitis B virus cause liver

      2. Human Papilloma virus causes cervical

      3. Epstein-Barr virus cause lymphoma

    2. These viruses may insert oncogene or inactive tumour-suppressive gene (cells continue to divide)

  3. Bacterial infection

    1. Helicobacter pylori cause cause stomach cancer

  4. Excessive hormone levels

    1. Higher estrogen may cause breast or cervical cancer

    2. Higher testosterone may cause prostrate cancer

  5. Genetic inheritance

    1. Some cancers are determined by genes that are inherited

      1. BRAC 1 oncogene, inherited from mother


Detection of Cancer

Physical exam

  • Breast and prostrate cancers

CT scans, MRI (tumour detection)

Biopsy of cell morphology

DNA testing

  • For the breast cancer gene, BRAC2, prostrate cancer gene (PSA)


Strategies to Fight Cancer

  1. Surgery

    1. To remove tumour, only if tumour has not metastasized

  2. Chemotherapy (kills other rapidly diving cells)

    1. To kill rapidly diving cells. Destroys spindle tubule formation. But is non-specific and damage occurs to hair follicles, bone marrow and intestinal cells

  3. Radiation

    1. To kill tumours by damaging their DNA. Cancer cells cannot repair DNA damage as well as normal cells

  4. Vaccines

    1. For cervical cancer (HPV vaccine)

  5. Targeted therapies

    1. Tyr and reduce growth of blood vessels towards tumours, reduce kinase activity levels, through drugs of various types

  6. Immunotherapy

    1. Use the immune system to fight off cancer cells with specific recognition of antigens on the surface of cancer cells (tumour-associated antigen)

  7. Active Immunotherapy

    1. Enhance the immune system to fight off cancer cells by adding interferon and interleukin (cytokines)

  8. Remove serum from blood that contains antibodies, purify them and add them back to the patient

  9. Radioimmunotherapy

    1. Attach radioactive isotopes to specific antibodies to deliver them directly to cancer cell to attach a drug to kill cell


Hope in Fighting Cancer

  • More we understand that biology of cancer cells the easier it will be to apply this knowledge

  • Immunotherapy holds a lot of promise

  • Environmental carcinogens that can induce mutations or change gene expression in humans are of increasing concern in our environment


CRISPR Technology

  • Edit the cancer gene and minimize the development

  • Still in medical studies





Review of Cancer

  • Cancer cells vs normal

    • What changes are seen

  • Factors that lead to cancer development

  • How it is diagnosed

  • What are treatments

  • What are opportunities to study and deal with the disease