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Non-small cell lung cancer (NSCLC)

Transforming growth factor-b receptor II
(TGFb-RII; TGFBR2); mediator complex subunit 12 (MED12)

In vitro studies suggest inhibiting TGFBR2 could help prevent resistance to targeted therapies in lung cancer. In NSCLC cells with activating mutations in anaplastic lymphoma kinase (ALK) or epidermal growth factor receptor (EGFR), knockdown of MED12, a transcriptional complex component mutated in some cancers, caused resistance to ALK and EGFR inhibitors and upregulated TGFBR2. In the MED12-/- NSCLC cells, a TGFBR2 inhibitor plus ALK or EGFR inhibitors sensitized the cells to therapy and synergistically inhibited cell growth. Next steps could include testing TGFBR2 inhibitors in animal models.

SciBX 5(47); doi:10.1038/scibx.2012.1233
Published online Dec. 6, 2012

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Huang, S. et al. Cell; published online Nov. 21, 2012;
Contact: René Bernards, The Netherlands Cancer Institute, Amsterdam, the Netherlands