Novel Mechanism of Taxane Resistance Found

U.S. scientists have found a gene affecting cancer cells’ sensitivity to chemotherapy — a key finding in the effort to increase chemotherapy effectiveness.

Research Associate Chih-Jian Lih and colleagues working in the laboratory of Stanley Cohen at Stanford University pinpointed the gene.

Using an approach that randomly alters expression of mammalian cell genes together with a screen that detects altered gene function, the researchers identified a previously uncharacterized gene, called txr1, whose increased expression in prostate cancer cells confers resistance to taxane drugs.

Taxanes are a class of widely-used chemotherapeutics — marketed as docetaxel and paclitaxel — that prevent cancer cell growth by inhibiting microtubule breakdown and subsequent cell division.

The researchers determined txr1 promotes taxane resistance by suppressing the anti-angiogenic and pro-apoptotic factor, thrombospondin 1 (TSP-1). That action is different from mechanisms found earlier to be involved in taxane resistance to taxanes.

As acquired drug resistance poses a major limitation to the long-term efficacy of taxanes, the discovery of txr1 as a component of a novel pathway of taxane cytotoxicity opens a new avenue to modulate chemotherapeutic drug response and sensitize cancer cells to drug treatment.

The research appears online at www.genesdev.org.