Yesterday, we introduced a study in which scientists in Sanford-Burnham’s NCI-Designated Cancer Center and Conrad Prebys Center for Chemical Genomics were looking for compounds that regulate invadopodia, cellular projections that allow cancer cells to invade and metastasize. They used robotic technology and automated microscopy to screen a library of pharmacologically active compounds—compounds already known to influence cellular function. In the course of the study, the researchers found some compounds that inhibit invadopodia and some that promote their formation. One of the latter was paclitaxel. Paclitaxel, also known by the brand name Taxol, is an FDA-approved drug currently used to treat several different kinds of cancer. The drug’s anti-tumor activity is based on its ability to bind and stabilize microtubules, one component of the cellular cytoskeleton, thereby halting cell division and inducing cellular suicide (a good thing, for cancer).
However, in this study, paclitaxel also promoted invadopodia formation and cancer cell invasion. While surprising, this makes sense because invadopodia formation also depends on microtubules, which are stabilized by paclitaxel. These results raise the concern that continued treatment with paclitaxel might be counterproductive in cancer patients who aren’t responding well to the drug or in cases where the tumor has not yet been removed. In fact, paclitaxel could actually provoke cancer metastasis in these patients.
“Although our results suggest paclitaxel might increase metastasis, we also observed that the drug did not promote invasive behavior in cells treated with an invadopodia inhibitor,” says Dr. Sara Courtneidge, the study’s senior author. “This defines a potential clinical path for testing inhibitors in the context of paclitaxel treatment. In other words, a patient could still benefit from paclitaxel’s cancer cell-killing effect if physicians also have the ability to add a therapeutic invadopodia inhibitor when resistance develops.”
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Original paper:
Quintavalle, M., Elia, L., Price, J., Heynen-Genel, S., & Courtneidge, S. (2011). A Cell-Based High-Content Screening Assay Reveals Activators and Inhibitors of Cancer Cell Invasion Science Signaling, 4 (183) DOI: 10.1126/scisignal.2002032
