Caroline Springer
Team Leader
Gene and Oncogene Targeting
The Institute Of Cancer Research
United Kingdom
Biography
Professor Caroline Springer leads a multidisciplinary team called Gene and Oncogene Targeting within the Division of Cancer Therapeutics at The Institute of Cancer Research (ICR). Her work focuses on the discovery of a wide range of novel therapeutics. After completing her PhD in biological chemistry at University College London, Professor Springer began work at the ICR on the novel ADEPT (antibody-directed enzyme prodrug therapy) treatment designed to target tumours selectively. The target tumour was colorectal carcinoma and this work led to four ADEPT clinical trials at Charing Cross, Royal Free and University College London Hospitals in London. Caroline also developed gene-directed enzyme prodrug therapy (GDEPT), a suicide gene therapy treatment that can be used in a wide range of cancer types. This work is now coming to fruition clinically with Professor Kevin Harrington in head and neck cancer.
Research Interest
Caroline is currently investigating several different therapeutic approaches including research into lysyl oxidase inhibitors, an enzyme that is important in invasion and metastasis. The goal is to prevent and treat metastases in a range of tumour types in collaboration with Professor Richard Marais. A series of LOX inhibitors are now in late lead optimisation. A key area of research has been to discover panRAF inhibitors for use in melanoma and colorectal cancers in collaboration with Professor Richard Marais. The new drug target entered clinical trials at The Royal Marsden with Professor Gore and Dr James Larkin and Christie Hospitals in 2015.
Publications
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Heidorn, S.J., Milagre, C., Whittaker, S., Nourry, A., Niculescu-Duvas, I., Dhomen, N., Hussain, J., Reis-Filho, J.S., Springer, C.J., Pritchard, C., et al. (2010). Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. Cell, Vol.140(2), pp. 209-221.
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Whittaker, S., Menard, D., Kirk, R., Ogilvie, L., Hedley, D., Zambon, A., Lopes, F., Preece, N., Manne, H., Rana, S., et al. (2010). A Novel, Selective, and Efficacious Nanomolar Pyridopyrazinone Inhibitor of (V600E)BRAF. Cancer res, Vol.70(20), pp. 8036-8044
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Suijkerbuijk, B.M., Niculescu-Duvaz, I., Gaulon, C., Dijkstra, H.P., Niculescu-Duvaz, D., Menard, D., Zambon, A., Nourry, A., Davies, L., Manne, H.A., et al. (2010). Development of Novel, Highly Potent Inhibitors of V-RAF Murine Sarcoma Viral Oncogene Homologue B1 (BRAF): Increasing Cellular Potency through Optimization of a Distal Heteroaromatic Group. J med chem, Vol.53(7), pp. 2741-2756.
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Viros, A., Hayward, R., Matthew, M., Yashar, S., Yu, C.C., Sanchez-Laorden, B., Zambon, A., Niculescu-Duvaz, D.M., Springer, C., Lo, R.S., et al. (2012). Topical 5-Fluorouracil Elicits Regressions of BRAF Inhibitor-Induced Cutaneous Squamous Cell Carcinoma. Journal of investigative dermatology, Vol.133(1), pp. 274-276
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Su, F., Viros, A., Milagre, C., Trunzer, K., Bollag, G., Spleiss, O., Reis-Filho, J.S., Kong, X., Koya, R.C., Flaherty, K.T., et al. (2012). RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N engl j med, Vol.366(3), pp. 207-215
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Sanchez-Laorden, B., Viros, A., Girotti, M.R., Pedersen, M., Saturno, G., Zambon, A., Niculescu-Duvaz, D., Turajlic, S., Hayes, A., Gore, M., et al. (2014). BRAF Inhibitors Induce Metastasis in RAS Mutant or Inhibitor-Resistant Melanoma Cells by Reactivating MEK and ERK Signaling. Science signaling, Vol.7(318), pp. ra30-ra3
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Girotti, M.R., Lopes, F., Preece, N., Niculescu-Duvaz, D., Zambon, A., Davies, L., Whittaker, S., Saturno, G., Viros, A., Pedersen, M., et al. (2015). Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma. Cancer cell, Vol.27(1), pp. 85-96.
