Summary
Team Leader: Molecular Therapy Laboratory
Euan gained a first class honours in Molecular Biology followed by a PhD in Medical Genetics from the University of Aberdeen. In 2000 he joined the Edinburgh Cancer Research UK Centre as a postdoctoral fellow. From there he moved to Imperial College in 2003 where he now runs the Molecular Therapy Lab within the Ovarian Cancer Action Research Centre. Euan is funded by Ovarian Cancer Action, the UK's leading ovarian cancer charity.
The Molecular Therapy Laboratory
The overall aim of the Molecular Therapy Lab is to apply an improved understanding of the molecular basis of chemoresistance in cancer for therapeutic target identification, mechanistic understanding and clinical implementation to improve the response rates and survival for patients with this disease.
Our previous work identified a way in which ovarian tumor cells inappropriately use a protein called DNA-PKcs to over activate another protein called AKT, which keeps tumor cells alive even when treated with chemotherapy. This work was followed up with siRNA screens to identify new targets and has led to drug development projects and clinical trials in which chemotherapy resistant ovarian cancer patients have been given drugs that inhibit the AKT protein. The first trial looked at AKT inhibition alone and the second combined AKT inhibition with standard chemotherapy to test if it makes patients respond better. We found that in a patient population in which we would expect 10% to respond to standard chemotherapy, 37% of patients responded when an AKT inhibitor was added.
The Lab is also very interested in the concept of intra-tumoural heterogeneity: that is, that the cells that make up a single patient’s cancer are not all the same and they do not all respond the same to chemotherapy. We are studying this in order to identify what makes the unresponsive cells within a tumor harder to kill with chemotherapy, but also to understand what drives them so we can make them respond better and identify them earlier.
Publications
Journals
Stronach EA, Cunnea P, Turner C, et al., 2015, The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma, Oncotarget, Vol:6, ISSN:1949-2553, Pages:31593-31603
Fotopoulou C, Cunnea P, Rama N, et al., 2014, CHARACTERISING PHENOTYPICALLY RELEVANT INTRATUMOURAL HETEROGENEITY IN HIGH GRADE SEROUS OVARIAN CANCER, International Journal of Gynecological Cancer, Vol:24, ISSN:1048-891X, Pages:443-444
Maginn EN, de Sousa CH, Wasan HS, et al., 2014, Opportunities for translation: Targeting DNA repair pathways in pancreatic cancer, Biochimica Et Biophysica Acta-reviews on Cancer, Vol:1846, ISSN:0304-419X, Pages:45-54
Cunnea P, Stronach EA, 2014, Modeling platinum sensitive and resistant high-grade serous ovarian cancer: development and applications of experimental systems, Frontiers in Oncology, Vol:4, ISSN:2234-943X
Conference
Curry E, Cheraghchi-Bashi-Astaneh A, Chen M, et al., 2015, DNA-PKcs is amplified in high-grade serous ovarian cancer (HGSC), correlates with poor outcome and drives resistance to platinum therapy via the AKT signaling pathway, AMER ASSOC CANCER RESEARCH, ISSN:1535-7163