(ChemotherapyAdvisor) – DUSP4 protein deficiencies in breast cancer may lead to resistance to chemotherapy, according to multinational team of researchers. The conclusion is based on a study entitled “Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance,” which was published online in Nature Medicine on June 10.
Although administering neoadjuvant chemotherapy (NAC) to patients with breast cancer induces a 30% pathological complete response (pCR), the other 70% of patients who do not achieve pCR have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer prognosis. The investigators hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance.
Several observations were made. First, the investigators reported that low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation that had become, diagnostically, a basal-like breast cancer (BLBC) status. On a molecular level, “DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy,” the investigators wrote. “Reduced DUSP4 expression in primary tumors after NAC correlated with treatment-refractoriness and shorter recurrence-free survival.”
In conclusion, breast cancers with deficiencies in the DUSP4 protein results in accelerated rates of post-NAC tumor cell proliferation, as well as treatment-refractoriness and shorter recurrence-free survival.