Research press release


Nature Medicine

Digitally mining tumors for therapy response markers



Carlos Arteagaたちは、ネオアジュバント化学療法後に外科的に切除した腫瘍のデジタルDNA定量を行って、予後不良で生存期間の短い乳がん患者では、発癌性情報伝達の負の調節因子であるDUSP4の量が減少していることを明らかにした。DUSP4減少の結果、発癌性のRas-ERK経路の活性化が起こり、癌細胞のアポトーシスを妨げる原因となるらしい。


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.

doi: 10.1038/nm.2795


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