Research ArticleNon–small cell lung cancer

Blocking NRG1 and Other Ligand-Mediated Her4 Signaling Enhances the Magnitude and Duration of the Chemotherapeutic Response of Non–Small Cell Lung Cancer

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Science Translational Medicine  06 Feb 2013:
Vol. 5, Issue 171, pp. 171ra18
DOI: 10.1126/scitranslmed.3004438

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Regaining the Yellow Jersey

Professional sports—from cycling to football and even baseball—are now cracking down on doping. The use of performance-enhancing drugs is thought to give an unfair advantage, and regulatory agencies are trying to return everyone to even ground. But whereas athletes who dope become pariahs, in some fights it’s better not to play fair. Now, Hegde et al. suggest a way to enhance chemotherapy in the fight against non–small cell lung cancer (NSCLC).

Chemotherapy is a first-line treatment for NSCLC but, in some cases, cannot either adequately remove the tumor or prevent recurrence. The authors use multiple models of NSCLC and find that residual tumor cells after chemotherapy express high levels of neuregulin 1 (NRG1), which is a ligand for human epidermal growth factor receptor 3 and 4 (HER3/4). Inhibited NRG1 signaling had only variable effects on primary tumor growth, but significantly enhanced the magnitude and duration of tumor response to chemotherapy. NRG1 inhibition in combination with chemotherapy greatly impeded relapse. Although this combination remains to be tested in the clinic, this study suggests that when it comes to a competition between NSCLC and chemotherapy, all’s fair.

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