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Researchers reveal underlying mechanism of powerful chemotherapy for prostate cancer treatment
Date:9/17/2012

receptor (AR), which is a driving force in prostate cancer growth and metastasis, "moves" along microtubules to be transported to the nucleus. When a taxane binds microtubules, it stops AR from traveling, thus inhibiting its activity. Taxane chemotherapy drugs such as paclitaxel, docetaxel and cabazitaxel work by binding tubulin, a protein that makes up microtubules. Microtubules are the rope-like channels that provide both a skeletal structure to cells as well as provide "highways" along which molecules, such as proteins, RNA complexes and vesicles, can travel from one part of the cell to another and interact with each other.

"Microtubules are the highly dynamic network of wires within cells, and when taxanes are used, the network stops moving," says Dr. Giannakakou. This is best observed when cancer cells attempt to divide, she says. "It is easy to see in the laboratory, that prostate cancer cells double every 30-48 hours, and taxane stops them from doing that, which pushes these cells to die. This leads everyone to think that this is exclusively how taxanes work they stop cells from dividing."

But Dr. Giannakakou and her research team point out in their new study that patients have significantly lower rates of cell division in their tumors than do cancer cells growing in the lab. In fact, cancer cells in prostate cancer patients only divide every 33-577 days, she says. "Thus, the therapeutic benefit of taxanes on microtubules depends on more than just stopping cell division."

The new insights provided by this study about the action of taxanes on AR trafficking helps explain the clinical activity of these drugs in the treatment of prostate cancer while at the same time can help researchers better understand why an individual patient might respond or not to taxane therapy. Such insights are critical for future chemotherapy customization, according to researchers.

The drug that was later named Taxol (pacilitaxel) was isolated from
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Contact: Lauren Woods
law2014@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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