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R I Nicholson, C Staka, F Boyns, I R Hutcheson, and J M W Gee

enhance response to estrogen deprivation and improve breast cancer survival. Growth factor signaling associates with resistance to endocrine therapies, including estrogen deprivation Developing breast cancer cells are bathed in a rich

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Barbara Kuske, Catherine Naughton, Kate Moore, Kenneth G MacLeod, William R Miller, Robert Clarke, Simon P Langdon, and David A Cameron

Introduction Estrogen receptor α (ERα) is a major growth regulator for many breast cancers and has provided an exploitable target for therapy ( Ali & Coombes 2002 ). Estrogen binding to ERα promotes conformational changes in the

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W R Miller, T J Anderson, S White, D Evans, A Krause, and J M Dixon

Introduction The Edinburgh Breast Unit has a major interest in identifying predictive indices of early response and resistance to endocrine therapy and their underlying mechanism of action. To investigate these in relevant clinical

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Penn Muluhngwi and Carolyn M Klinge

significant increase in disease-free survival ( Cuzick et al . 2010 , Regan et al . 2011 ). Unfortunately, the effectiveness of TAM and AI therapy is limited, as seen in the relapse of ∼40% of patients ( 1998 ). When resistance occurs, it is unclear which

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Jill I Murray, Nathan R West, Leigh C Murphy, and Peter H Watson

( Zwart et al . 2011 ). ESR1-positive tumours account for approximately 70% of cases at diagnosis and are candidates for endocrine therapies. However, ESR1-positive tumours can manifest resistance at the outset or become resistant to endocrine therapy

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Conleth G Murphy and Maura N Dickler

manipulation of the ER pathway, with approximately 20% of HR+ metastatic breast cancers (MBC) proving refractory to first-line endocrine therapy ( McGuire et al. 1977 ). Furthermore, the emergence of resistance to endocrine manipulation is inevitable with

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Eliot B Blatt, Noa Kopplin, Shourya Kumar, Ping Mu, Suzanne D Conzen, and Ganesh V Raj

, darolutamide) and antiestrogens targeting ER (tamoxifen, fulvestrant) have shown efficacy in and improved survival for patients. However, these drugs are rarely curative and endocrine therapy resistance is common, as cancer cells evolve mechanisms to maintain

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Luis V Syro, Fabio Rotondo, Leon D Ortiz, and Kalman Kovacs

frequently asked questions about TMZ treatment, duration of therapy, dosage, tumor recurrence and resistance ( Bruno et al . 2015 ). Aggressive adenomas and pituitary carcinomas PAs are a heterogenous group of lesions with different clinical

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Iain R Hutcheson, Janice M Knowlden, Helen E Jones, Rajpal S Burmi, Richard A McClelland, Denise Barrow, Julia M W Gee, and Robert I Nicholson

/AKT-signalling pathway as a potential mediator of resistance to anti-growth factor therapies, including those targeting EGFR ( Chakravarti et al. 2002 , Bianco et al. 2003 , She et al. 2003 , Jones et al. 2004 , Camirand et al. 2005 ). Elevated levels of

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Neil Portman, Sarah Alexandrou, Emma Carson, Shudong Wang, Elgene Lim, and C Elizabeth Caldon

in breast cancer mortality by approximately 40% ( Early Breast Cancer Trialists’ Collaborative Group 2015 ). However, resistance to endocrine therapy leading to early stage ER+ breast cancer recurrence is not uncommon and inevitable in the setting of