Cancer

What is Cancer?

• A diverse collection of diseases characterized by uncontrolled division of abnormal cells that can invade nearby tissues and spread through the blood and lymph systems to distance sites

• Common properties:

  • Divide uncontrollably

  • Invade and colonize locations normally reserved for other cells → metastasize

  • Most forms of cancer involve multiple genetic changes

Types of Cancer - usually named for organs or tissues where the cancer forms

Carcinoma: Most common, begins in the skin cells or in tissues that line or cover internal organs, e.g. Adenocarcinoma forms in epithelial cells that produce fluid or mucus (breast, colon, prostate)

Sarcoma: Begins in bone, cartilage, and soft tissues, including muscle, fat, blood vessels, tendons, ligaments

Leukemia: Begins in blood forming tissue of the bone marrow. Do not form solid tumors. Large numbers of abnormal white blood cells build up blood and bone marrow, crowding out normal blood cells

Lymphoma: Begins in lymphocytes (T cells or B cells), the disease-fighting white blood cells of the immune system

• Cancer is genetic on a cellular level

  • Most cancers originate in a single cell via mutation

  • A cancer cell divides to generate two cancer cells

  • Cancer originating in somatic cells is NOT inherited

  • But, a genetic predisposition for cancer can be inherited — inherited mutations make it more likely that cancer will develop

• Cancer is deregulation of cell division — lack of cell cycle control → over-proliferation

Mitotic Cell Cycle

Protein Regulators

• Positive regulators: Increases cell division

  • Too much → too much cell proliferation → cancer

• Negative regulators: Decreases cell division

  • Too little → too little control on cell division → cancer

• * Often multiple genetic changes required for cancer to result

Proto-oncogenes (normal): the (+) regulators or accelerators

• Oncogenes (gain-of-function): Mutated gene whose mis-expression can lead to rampant cell division and contribute to cancer → too much activity, cell division is unregulated

• Too many copies of the normal proto-oncogene can also lead to uncontrolled cell division

• Treatment for some HER2+ cancers: HERCEPTIN

  • An antibody that selectively binds to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2, prevents EGF (Human Epidermal Growth Factor) to bind

  • *To treat the cancer, the specific mutation must be known

Tumor Suppressor Genes: the (-) regulators or brakes

• Genes whose normal function is to prevent uncontrolled cell proliferation, so reduced function can lead to cell overgrowth

• Retinoblastoma: tumor in the retina

  • Inheritance is Autosomal Dominant, but some individuals with the dominant gene do not develop a tumor — incomplete penetrance

  • Inheritance of a mutant allele INCREASES risk of developing a tumor

  • Some Tumor Suppressor genes can be involved in familial AND sporadic cancer of a particular organ/tissue such as breast, colon or retina

    • TSG mutations can be inherited in a dominant fashion, but they are recessive at the level of the cell — tumor formation requires TWO mutant alleles

    • Familial: Inherit one mutant allele from a parent (1 genetic) second mutant allele develops in somatic tissue (1somatic)

    

    • Sporadic: BOTH mutant alleles develop in somatic tissue, not transmitted to offspring (both copies somatic)

      

• Most forms of cancer involve multiple genetic changes, leading to malignancy — cancer development is a multistep process !!

  • Growth begins as a small benign growth (polyp), too much or too little regulators would affect the growth