Sequence matters when using novel agent

one of three different chemotherapy drugs, Etoposide, Doxorubicin, and Paclitaxel.

Unlike Etoposide and Doxorubicin, which both have similar mechanism of action by disrupting the function of certain enzymes involved in DNA processing, Paclitaxel works by disrupting a microtubular system, which is key for the normal function of the cell.

The researchers found that it did not matter whether PS-341 was given first, last, or in combination with either Doxorubicin or Etoposide. The combinations worked synergistically on both cell death and growth inhibition in cultures of advanced prostate cancer cells.

However, their findings with the third chemotherapy agent, Paclitaxel, argued that PS-341 should not be used after Paclitaxel because that order of use conferred a protective effect on cancer cells by reducing their rate of cell death. The reason for this is not completely understood yet, "but it could partly be explained by the opposing effect Paclitaxel and PS-341 have on the key microtubular proteins MAP-4 and beta-Tubulin that are necessary for the anti-tumor activity of Paclitaxel," Papandreou says.

This may be important because taxane-based therapies, such as Taxol, and Taxotere, are widely used to treat many malignancies, including prostate and bladder cancers, he says.


Contact: Laura Sussman
University of Texas M. D. Anderson Cancer Center

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