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Ng T.,Guys Medical School Campus | Ng T.,Breakthrough Breast Cancer Research Unit | Irshad S.,Guys Medical School Campus | Irshad S.,Breakthrough Breast Cancer Research Unit | Stebbing J.,Imperial College London
Oncogene | Year: 2013

The multifunctional roles of BRCA1 include its ability to regulate transcriptional processes that control differentiation at multiple levels, as well as functioning as a tumor suppressor. Data herein demonstrate that germline mutations in Brca1 impair luminal cell lineage and mammary development, with its deficiency converting ER-positive luminal tumors into basal-like cancers. Heterozygous mutations in Brca1 lead to downregulation of a number of luminal differentiation genes, explaining how it suppresses basal-like tumors, also highlighting its importance outside of its known highly publicized role in DNA repair. © 2013 Macmillan Publishers Limited All rights reserved.

Claus J.,Cancer Research UK Research Institute | Patel G.,Guys Medical School Campus | Ng T.,Guys Medical School Campus | Parker P.J.,Cancer Research UK Research Institute
Biochemical Society Transactions | Year: 2014

Specific inhibition of members of the EGFR (epidermal growth factor receptor) family, particularly EGFR and HER2 (human epidermal growth factor receptor 2), are an important therapeutic strategy in many human cancers. Compared with classical chemotherapy, these targeted therapeutics are very specific and initially effective, but acquired resistance against these targeted therapies is a recurring threat. A growing body of recent work has highlighted a pseudokinase in the EGFR family, HER3, and its ligand, NRG (neuregulin β1), to be of importance in models of resistant cancers, as well as in patients. In the present article, we describe some of the roles in which HER3 can mediate acquired resistance and discuss the current efforts to target HER3 itself in cancer. © The Authors Journal compilation © 2014 Biochemical Society.

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