New Option Seen Possible for Colon Cancer Patients Resistant to Paclitaxel

Patients with colon cancer or breast cancer who are resistant to paclitaxel may be successfully treated with semisynthetic taxane IDN-5109, according to researchers at the Roswell Park Cancer Institute in Buffalo, New York.

Researchers studied two lines of cultured breast cancer cells, one that expressed P-glycoprotein, which removes paclitaxel from the cells. They incubated each cell set separately with tritiated IDN-5109 and with tritiated paclitaxel.

Researchers reported that, in the cells that expressed P-glycoprotein, treatment with IDN-5109 resulted in retention of more P-glycoprotein substrates than those treated with paclitaxel. These cells retained a level of IDN-5109 that was 5 times more than that of paclitaxel after incubation for 2 hours, according to the study published in the Journal of the National Cancer Institute.

The study showed that cells not expressing P-glycoprotein did not retain increased amounts of the substrates no matter which agent was used. Researchers speculate that IDN-5109 binds to P-glycoprotein, allowing IDN-5109 to accumulate in the cancer cells.

Researchers concluded that IDN-5109 modulates P-glycoprotein activity, resulting in superior inhibition of tumor growth against P-glycoprotein-expressing tumors compared with paclitaxel. IDN-5109 may broaden the spectrum of taxane use to include colon tumors.