Title

Sarah Blagden

Cancer Therapeutics and mRNA Dysregulation

Investigating post-transcriptional mechanisms that drive cancer behaviour and researching novel cancer therapeutics for patients with advanced malignancies.

Email: 
sarah.blagden@oncology.ox.ac.uk
Telephone: 
+44 (0) 1865 235311 PA
PA: 
Tuija Vanttinen-Newton
Email PA: 
patosarahblagden@oncology.ox.ac.uk

Research Summary

mRNA dysregulation in Cancer: Gene expression describes the conversion of genetic message to protein. This depends on messenger RNA (mRNA) which copies the gene sequence, shuttles into the cytoplasm, binds ribosomes and generates protein. Numerous RNA binding proteins (RBPs) attach to these mRNA transcripts and regulate their splicing, stability, subcellular localisation and rate of translation. In cancer cells, expression of RBPs is disrupted, driving the malignant state by preserving the stability of proto-oncogenic mRNAs while destabilising those with tumour suppressor functions. One such RBP is La-related protein 1 (LARP1). We have shown that LARP1 is capable of selectively binding transcripts involved in cancer processes and is present at high levels in some epithelial cancers. The net effect of LARP1 upregulation is to drive cancer progression. The purpose of our research is to discover more about cancer RBPs and develop therapeutics against them that can be used as anti-cancer treatments.

LARP1 (green) highly expressed in the cytoplasm of a cancer cell. LARP1 is associated with almost 3000 mRNAs predominantly those encoding cancer signalling proteins.

Cancer Therapeutics: A crucial part of cancer drug discovery is finding the best cancer treatments for the future. In leading the Early Phase Trials Unit, Dr Blagden’s team investigate new treatments for patients with cancer. Potential treatments are carefully chosen on their scientific rationale, their likelihood of being effective and, most importantly, their safety profile. The Oxford Early Phase Cancer Trials Unit has a long established track record of drug discovery and delivering novel therapies safely and effectively. Dr Blagden has a strong science and medical background which enables her to design clinical trials, investigate treatments (developed by academia or industry) and deliver them to cancer patients.

LARP1 (stained green here) relocates to cytoplasmic stress granules following exposure to cell stress in ovarian cancer cells

Biography

Sarah Blagden has been Associate Professor of Experimental Cancer Therapeutics in the Department of Oncology since 2015. Following medical training and subsequent specialist training in Medical Oncology at Addenbrooke’s Hospital in Cambridge and the Royal Marsden Hospital, she was awarded a CRUK Junior Clinician Scientist PhD fellowship in 1999 at Cambridge University and held a Clinical Fellowship at the Institute of Cancer Research’s Drug Development Unit.

She was appointed as Senior Lecturer and Honorary Consultant at Imperial College in 2006 and became Director of Imperial’s Early Cancer Trials Unit and established her laboratory studying the dysregulation of mRNA translation in cancer. She has been chief or principal investigator for a number of national and international clinical studies

 

Publications

SELECTED PUBLICATIONS:

Rizzuto I, Stavraka C, Chatterjee J, Borley J, Glass-Hopkins T, Gabra H, Ghaem-Maghami S, Huson L, Blagden SP. Risk of Ovarian Cancer Relapse (ROVAR) Score: A prognostic algorithm to predict relapse following treatment for advanced ovarian cancer. Accepted for publication by Int J Gynecol Cancer, Jan 2015

Mura M, Hopkins TG, Michael T, Abd-Latip N, Weir J, Aboagye E, Mauri F, Jameson C, Sturge J, Gabra H, Bushell M, Willis A, Curry E, Blagden S. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene. Dec 2014.

Blagden S, Omlin A, Josephs DH, Stavraka C, Zivi A, Pinato DJ, Anthoney DA, Decordova S, Swales K, Riisnaes R, Pope L, Noguchi K, Shiokawa R, Inatani M, Prince J, Jones K, Twelves CJ, Spicer JF, Banerji U. First-in-Human study of CH5132799, an Oral Class I PI3K Inhibitor, Studying Toxicity, Pharmacokinetics and Pharmacodynamics, in Patients with Metastatic Cancer. Clin Cancer Res. 2014 Sep 17

Borley J, Wilhelm-Benartzi C, Yazbek J, Williamson R, Bharwani N, Stewart V, Carson I, Hird E, McIndoe A, Farthing A, Blagden S, Ghaem-Maghami S. Radiological predictors of cytoreductive outcomes in patients with advanced ovarian cancer. BJOG. 2014 Aug 5.

Associated Researchers

Group members:

James Chettle, Postdoctoral Researcher
Mai Abdei Mouti, Post Doctoral Researcher

 

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