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Feb 21, 2013
 |  BC Innovations  |  Cover Story

NRG1 meets resistance

Researchers at Roche's Genentech Inc. unit have shown that the receptor tyrosine kinase ligand neuregulin 1 can drive resistance to chemotherapy in non-small cell lung cancers. Although the precise mechanism is being worked out, countering resistance by hitting neuregulin 1 or its receptors in conjunction with conventional chemotherapy could prevent chemo resistance.1

Neuregulin 1 (NRG1) is an autocrine signaling factor that normally promotes survival and differentiation in developing tissues. The protein acts on several receptors, including epidermal growth factor receptor 3 (EGFR3; HER3; ErbB3) and HER4 (EGFR4; ErbB4), and recently has turned up as a marker of EGFR inhibitor resistance in several tumor types.2

Now, a team led by Genentech principal scientist Erica Jackson has found that NRG1 signaling through HER3 and HER4 is more than just a marker and actually drives chemotherapeutic resistance in non-small cell lung cancer (NSCLC).

Although the specific mechanism of how the pathway protects tumor cells remains unclear, the company has shown that NRG1-blocking mAbs can prevent the emergence of chemo-resistant tumor cells.

Jackson's team found that NRG1-HER3/HER4 signaling was higher in tumor cells that had survived a course of chemotherapy than in treatment-naïve tumors.

The group suspected that these cells were present in the original tumor and proliferated after chemotherapy, which killed off the cells lacking this pathway but left NRG1-overexpressing cells intact.

Indeed, in...

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