Lower amounts of an enzyme called DUSP4 are associated with resistance to neadjuvant chemotherapy-which is given before surgical tumor removal-and aggressive breast cancers, reports a paper published online this week in Nature Medicine. Further validation in clinical trials will confirm whether DUSP4 could be a potential marker of therapy outcome.

Neadjuvant chemotherapy, which is given before surgical tumor removal, can reduce the size of the tumor. But many patients do not have a complete response and show residual cancer after this treatment and an increased risk for metastatic disease.

Using digital DNA quantification in surgically-resected tumors after neo-adjuvant chemotherapy, Carlos Arteaga and colleagues show that the levels of DUSP4, a negative regulator of oncogenic signaling, are decreased in breast cancer patients with poor outcome and short survival. Activation of the oncogenic Ras-ERK pathway seems to be the result of decreased DUSP4, causing impaired cancer cell apoptosis.

The findings suggest that this signaling pathway may be targeted to improve the response to chemotherapy.