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Targeted Therapies for Prostate Cancer Tutorial

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Taxane combination therapies

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Normal apoptosis

Control of normal cell growth involves a process called apoptosis, or programmed cell death. In adults, the number of body cells is kept relatively constant. Stressed, diseased, malfunctioning or irreversibly damaged cells, as well as cells that need to be removed routinely as part of normal body maintenance or development, are all removed by apoptosis.

Shown is a layer of pink normal cells. One of the cells is fragmented into small vesicles, indicating that it has undergone apoptosis. Screen text reads: Apoptosis is programmed cell death.

Cells supervise their own destruction through a controlled and highly regulated series of steps.

The apoptotic cell shrinks & rounds up. It then condenses its DNA and cuts it into fragments. Finally, the cell breaks into small vesicles that can be easily engulfed by immune cells.

Shown is layer of pink normal cells. In the center of the image there is a close-up of a cell that has fragmented into small vesicles, indicating that it has undergone cell death or apoptosis.

 

Targeting tubulin & Bcl-2 to trigger apoptosis

The goal of targeted therapies that promote apoptosis is to tip the balance for cancer cells in favor of cell death. Taxotere® (generic drug name docetaxel) is a chemotherapy drug that promotes apoptosis in various ways.

Shown is a layer of pink normal cells with an embedded mass of green cancer cells. Several of the cancer cells have fragmented into small gray vesicles, indicating that they have undergone apoptosis. Screen text reads: The goal of therapies that promote apoptosis is to tip the balance toward cell death.

In normal cell division, or mitosis, structures called microtubules play an essential role in ensuring that each progeny cell receives a complete copy of DNA. In this process, microtubules assemble and disassemble in an orchestrated way.

Shown is a close-up of a cell during cell division, or mitosis. Inside the two hemispheres of the dividing cell are microtubule structures radiating like the spokes of a wheel from opposing poles. The microtubules are ready to move the cell's DNA to opposing poles in an orchestrated way. In the background is a layer of pink cells. Screen text reads: Mitosis (cell division) in normal cells.

Taxotere® binds to the protein tubulin, which is the building block of microtubules, and promotes microtubule formation. It also blocks microtubule disassembly, thereby "freezing" the structures. This results in the inhibition of mitosis in cells and eventually triggers apoptosis.

Shown is a close-up of a dividing cancer cell in the presence of Taxotere. Inside the two hemispheres of the dividing cell are microtubule structures radiating like the spokes of a wheel from opposing poles. Taxotere has frozen the microtubule structures, inhibiting cell division. In the background is a layer of green cancer cells.

Shown is a close-up of a cancer cell in the presence of Taxotere with frozen microtubule structures. The inhibition of cell division has caused the cell to self-destruct. In the background is a layer of green cancer cells.

In addition to interfering with normal tubulin function, Taxotere® inactivates the pro-survival protein Bcl-2. This inactivation allows cell death, or apoptosis, to occur.

 

Taxane combination therapy triggers apoptosis

Taxotere® in combination with prednisone is approved by the FDA for the treatment of patients with metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer is cancer that has spread throughout the body, beyond the prostate alone, and continues to grow, even when testosterone is inhibited.

Shown in the background is a magnification of actual prostate cancer cells stained purple. Screen title reads: Metastatic castration-resistant prostate cancer. First bullet reads: Is cancer that has spread throughout the body. Second bullet reads: Continues to grow even when testosterone is inhibited.

The "best" chemotherapy for a patient with metastatic castration-resistant prostate cancer combines treatment with taxanes and prednisone. Clinical trials showed that this combination improved both survival and the length of time a patient remained disease-free when compared with the previous therapy, which combined mitoxantrone and prednisone.

Shown is an image of the head and shoulders of a male patient in a hospital bed. Screen text reads: The 'best' chemotherapy for a patient with metastatic castration-resistant prostate cancer combines treatment with taxanes and prednisone.

The taxanes that are used in this setting are Taxotere® and Jevtana (generic drug name cabazitaxel). Jevtana is a new microtubule inhibitor specifically approved for the treatment of prostate cancer in patients who were previously treated with a docetaxel-containing treatment regimen.

Shown is a close-up of a dividing cancer cell in the presence of Taxotere. Inside the two hemispheres of the dividing cell are microtubule structures radiating like the spokes of a wheel from opposing poles. Taxotere has frozen the microtubule structures, inhibiting cell division. In the background is a layer of green cancer cells. Screen text reads: Jevtana® is a new microtubule inhibitor specifically approved for the treatment of prostate cancer.

Self Test

Questions

  1. How does docetaxel target prostate cancer?
    1. This drug blocks the microtubules from forming in mitosis.
    2. This drug blocks the microtubules from disassembling in mitosis.
    3. This drug inactivates the pro-survival protein called Bcl-2.
    4. Both B and C.

Answers

  1. How does docetaxel target prostate cancer?
    1. This drug blocks the microtubules from forming in mitosis. Incorrect.The answer is D (both B and C).
    2. This drug blocks the microtubules from disassembling in mitosis. There is a better answer.
    3. This drug inactivates the pro-survival protein called Bcl-2. There is a better answer.
    4. Both B and C. Correct.