Cancer

What is Cancer?

• Cancer is the deregulation of normal cellular processes.  Cells that have been transformed tend to proliferate in an uncontrolled and deregulated way and, in some cases, to metastasize (spread). 
• Cancer is not one disease, but a group of more than 100 different and distinctive diseases.
• Cancer can involve any tissue of the body and take on many different forms in each area.

Cancer is the 2nd leading cause of death in the U.S., surpassed only by heart disease.

What Happens in Cancer Cells?

• Cancer cells become deregulated in many ways

One way:

Mutations in one or more mitotic checkpoints allow the cell to move from one phase of mitosis to another unchecked.

Another way:

Mutations in cellular machinery itself so that mitotic errors are not properly detected/repaired, and the cell is allowed to move through mitosis unchecked.

Characteristics of Cancer Cells

• Cancer involves the development and reproduction of abnormal cells
• Cancer cells are usually nonfunctional
• Cancer cell growth is not subject to normal body control mechanisms
• Cancer cells eventually metastasize to other organs via the circulatory and lymphatic systems

Proliferation of cells

• Proliferating cells; Based on the DNA changes in cells, proliferating cycle of tumor cells can be divided into 4 phases
• Pre-synthetic phase (Gap 1 phase or G1 phase). Cells chiefly make preparations for the synthesis of DNA.
• Synthetic phase (S phase). Cells are synthesizing their DNA.
• Post-synthetic phase (Gap 2 phase or G2 phase). DNA duplication has been finished and they are equally divided to the two of future sub-cells.
• Mitosis phase (M Phase). each cell is divided into two sub cells. Some of these new cells enter the new proliferating cycle, the others become non-proliferating cells.

Non-proliferating cells

•  Non-proliferating cells include G0 phase cells (Resting-phase cells)
• G0 phase cells have proliferation ability but do not divide temporarily
•  When proliferating cells are suffered heavy casualties, G0 phase cells will get into proliferating cycle and become the reasons of tumor recurrence
•  G0 phase cells are usually not sensitive to antineoplastic drugs, which is an important obstacle to treat tumor with chemotherapy

Stages of Mitosis

• Interphase: Technically not part of mitosis, but rather encompasses stages G1, S, and G2 of the cell cycle which prepare the cell for mitosis.
• Prophase: Chromatin in nucleus condense; nucleolus disappears. Centrioles begin moving to opposite ends of the cell and fibers extend from the centromeres.
• Metaphase: Spindle fibers align the chromosomes along the middle of the cell nucleus. This line is referred to as the ‘metaphase plate.’
• Anaphase: The paired chromosomes separate at the kinetochores and move to opposite sides of the cell. Motion results from the physical interaction of polar microtubules.
• Telophase: Chromatids arrive at opposite poles of cell, and new membranes form around the daughter nuclei.  The chromosomes disperse.
• Cytokinesis: Results when a fiber ring composed of a protein called actin around the center of the cell contracts, pinching the cell into two daughter cells, each with one nucleus.

Mitosis Summary

• Mitosis is the process by which a cell duplicates the chromosomes in its cell nucleus to generate two, identical, daughter nuclei.
• It is followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles, and cell membrane into two daughter cells containing roughly equal shares of these cellular components.
• Mitosis and cytokinesis together define the mitotic (M) phase of the cell cycle.
• Mitosis is a normal cellular process necessary to sustain life, but its deregulation in one form or another is found in all cancer cells. 
• Mitosis can often become abnormal by the change in, or absence of, the normal mitotic checkpoints.

Mitotic Checkpoints

• Mitotic checkpoints are points in the cell cycle which act to ensure correct transmission of genetic information during cell division.  These checkpoints look for abnormalities within the cycle, specifically chromosomal aberrancy (deviation from normal course).
• Checkpoints take place towards the end of each phase of mitosis and must be passed before the cell can get clearance to enter the next stage of mitosis.
• If errors are found during checkpoints, the cell acts quickly to correct them, arresting cell growth and not proceeding with mitosis until the error has been fixed.

If these errors cannot be fixed, the cell normally undergoes apoptosis, or programmed cell death.

How ‘Cancer’ Arises

• The cell is allowed to move through the cell cycle and grow unchecked, and more mutations are accumulated over time that extend past the cell cycle to the cellular machinery itself.
• These mutations, in combination with the genetic mutations accrued through abnormal mitotic progression, eventually cause the cell to be completely deregulated in its growth and proliferation.
• It becomes unstoppable and even immortal.

Types of Cancer

Categorized based on the functions/locations of the cells from which they originate:

1. Carcinoma – skin or in tissues that line or cover internal organs. E.g., Epithelial cells. 80-90% reported cancer cases are carcinomas.
2. Sarcoma – bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.
3. Leukemia – White blood cells and their precursor cells such as the bone marrow cells, causes large numbers of abnormal blood cells to be produced and enter the blood.
4. Lymphoma – cells of the immune system that affects lymphatic system.
5. Myeloma – B-cells that produce antibodies- spreads through lymphatic system.
6. Central nervous system cancers – cancers that begin in the tissues of the brain and spinal cord.

Treatment of Cancer

• Surgery to remove solid tumors
• Radiation to kill cancer cells that have spread to adjacent local or regional tissues
• Chemotherapy to kill cancer cells located throughout the body
• Antineoplastic drugs cannot differentiate between normal and cancerous cells

New types of cancer treatment

• Hormonal Treatments: These drugs are designed to prevent cancer cell growth by preventing the cells from receiving signals necessary for their continued growth and division. E.g., Breast cancer – tamoxifen after surgery and radiation
• Specific Inhibitors: Drugs targeting specific proteins and processes that are limited primarily to cancer cells or that are much more prevalent in cancer cells.
• Antibodies:  The antibodies used in the treatment of cancer have been manufactured for use as drugs. E.g., Herceptin, avastin
• Biological Response Modifiers: The use of naturally occuring, normal proteins to stimulate the body’s own defenses against cancer. E.g., Abciximab, rituxmab
• Vaccines: Stimulate the body’s defenses against cancer. Vaccines usually contain proteins found on or produced by cancer cells.  By administering these proteins, the treatment aims to increase the response of the body against the cancer cells.