Professor Karen Brown

Karen is director of the Leicester Cancer Research Centre and joint lead of the Leicester Experimental Cancer Medicine Centre. She established and is co-chair of the UK Therapeutic Cancer Prevention Network and represents this network on the steering group of the Cancer Prevention Europe Consortium.

Karen’s research focusses on the discovery and preclinical development of agents for the prevention of cancer in populations at increased risk. She works to optimise the translation of these therapies to the clinic where she conducts early and late phase trials. Karen is currently leading COLO-PREVENT, a world-first prevention trial platform that will investigate the ability of resveratrol, aspirin and metformin to prevent colorectal polyps in high-risk patients. This trial is funded by Cancer Research UK and will be conducted across 60 sites in England and Wales.

Karen sits on several national and international grant panels and is currently a member of the Cancer Research UK Prevention and Population Research Committee and Vice-Chair of an Expert Review Panel for this committee.  She is a member of the World Cancer Research Fund International Regular Grant Programme Panel and Breast Cancer Now Grants Committee. Karen is also a former President of the United Kingdom Environmental Mutagen Society and currently sits on the committee as past-president.

Karen originally trained as a pharmacist and is currently professor of translational cancer research at the University of Leicester, where she leads the multidisciplinary Cancer Prevention Group. Her research is focussed on the discovery and preclinical development of agents for the prevention of cancer in populations at increased risk, optimising the translation of these therapies to the clinic and conducting early and late phase trials. She has an interest in both natural compounds such as curcumin and resveratrol and existing drugs that can be repurposed for cancer prevention. Intrinsic to her work is the discovery and development of pharmacodynamic biomarkers for monitoring activity in humans and personalising interventions. She has an emphasis on using clinically relevant models, such as primary explant cultures, informed by reverse translation of trials results. She also has an interest in the role of metabolic health in cancer development and how this interacts with preventive therapies to influence efficacy. Her research over the last 15 years has culminated in her securing Cancer Research UK funding  for COLO-PREVENT, a world first platform prevention trial of resveratrol, aspirin and metformin in high-risk patients, which will be conducted across 60 sites and includes an embedded programme of translational research focussed on precision prevention.

During her PhD and postdoctoral training at the MRC Toxicology Unit (Leicester) and Lawrence Livermore National Laboratory (California), Karen worked in the area of DNA damage and chemical carcinogenesis. She focussed on understanding how environmental chemicals (ethylene oxide), certain drugs (tamoxifen) and constituents of our diet (heterocyclic amines) can cause DNA damage and how this might contribute to cancer, with a view to preventing exposure and reducing cancer risk. She now brings this mechanistic understanding and expertise gained in analytical chemistry to the area of therapeutic prevention. 

Recent and key publications include the following:

Therapeutic prevention

• Cai H, Scott EN, Britton RG, Parrott E, Ognibene TJ, Malfatti M, Khan M, Steward WP, Brown K. (2021) Distribution and metabolism of [¹⁴C]-resveratrol in human prostate tissue after oral administration of a ‘dietary-achievable’ or ‘pharmacological’ dose: what are the implications for anticancer activity? Am J Clin Nutr. DOI 10.1093/ajcn/nqaa414.
• Ling S, Brown K, Miksza JK, Howells LM, Morrison A, Issa E, Yates T, Khunti K, Davies MJ, Zaccardi F (2021) Risk of cancer incidence and mortality associated with diabetes: A systematic review with trend analysis of 203 cohorts. Nutr Metab Cardiovasc Dis 31(1):14-22
• Howells L, Mukhtyar RM, Theofanous D, Pepper C, Gescher A, Thomas A, Brown K, Khan S. (2021) A systematic review assessing clinical utility of curcumin with a focus on cancer prevention. Mol. Nutr. Food Res 65(13):e2000977. doi: 10.1002/mnfr.202000977.
• Briata IM; Paleari L; Rutigliani M; Petrera M; Caviglia S; Romagnoli P; Libera MD; Parodi A; Oppezzi M; Coccia G; Giuliano S; Buttiron-Webber T; Castellaro L; Puntoni M; Siri G; Lazzeroni M; Howells L; Singh R; Brown K; DeCensi A (2021) A presurgical study of curcumin combined with anthocyanin supplements in patients with colorectal adenomatous polyps. Int. J. Mol. Sci. 22 (20), 11024; https://doi.org/10.3390/ijms222011024
• Ling S, Brown K, Miksza JK, Howells LM, Morrison A, Issa E, Yates T, Khunti K, Davies MJ, Zaccardi F. (2020) Association of Type 2 Diabetes With Cancer: A Meta-analysis With Bias Analysis for Unmeasured Confounding in 151 Cohorts Comprising 32 Million People. Diabetes Care 43(9): 2313-2322.
• Howells LM, Iwuji COO, Irving GRB, Barber S, Walter H, Sidat Z, Griffin-Teale N, Singh R, Foreman N, Patel SR, Morgan B, Steward WP, GescherA, Thomas AL, Brown K. (2019) Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial. J Nutr 00:1–7. doi.org/10.1093/jn/nxz029
• Moe Myint NN, Verma AM, Tarpey PS, Al-Aqbi SS, Cai H, Trigg R, West K, Howells LM, Thomas A, Brown K, Guttery DS, Singh B, Pringle HJ, McDermott U, Shaw JA, Rufini A. (2018) Circulating tumor DNA in patients with colorectal adenomas: assessment of detectability and genetic heterogeneity. Cell Death Dis. 9:894.
• Smith SG, Foy R, McGowan J, Kobayashi LC, deCensi A, Brown K, Side L, Cuzick J. (2017) Prescribing tamoxifen in primary care for the prevention of breast cancer: a national online survey of GPs’ attitudes. British Journal of General Practice, 67 (659): e414-e427. doi.org/10.3399/bjgp17X689377.
• Cai H, Scott E, Kholghi A, Andreadi C, Rufini A, Karmokar A, Britton RG, Horner-Glister E, Greaves P, Jawad D, James M, Howells L, Ognibene T, Malfatti M, Goldring C, Kitteringham N, Walsh J, Viskaduraki M, West K, Miller A, Hemingway D, Steward WP, Gescher AJ, Brown K. (2015) Less is more for cancer chemoprevention: evidence of a non-linear dose response for the protective effects of resveratrol in humans and mice. Sci. Transl. Med. 7, 298ra117.
• James MI, Iwuji CO, Irving GR, Karmokar A, Higgins JA, Griffin-Teale N, Thomas A, Greaves P, Cai H, Patel SR, Morgan B, Dennison A, Metcalfe M, Garcea G, Lloyd DM, Berry DP, Steward WP, Brown K (2015) Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett., 364, 135-141.
• James MI, Howells LM, Karmokar A, Higgins JA, Greaves P, Cai H, Dennison A, Metcalfe M, Garcea G, Lloyd D, Berry DP, Steward WP, Brown K (2015) Characterization and propagation of tumor initiating cells derived from colorectal liver metastases: trials, tribulations and a cautionary note. PLoS ONE 10(2): e0117776. doi:10.1371/journal.pone.0117776.
• Patel KR, Andreadi C, Britton RG, Horner-Glister E, Karmokar A, Sale S,Brown VA, Brenner DE, Singh R, Steward WP, Gescher AJ, Brown K (2013) Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence. Sci. Transl. Med. 5, 205ra133.
• Irving GRB, Howells LM, Sale S, Kralj-Hans I, Atkin W, Clark S, Britton RG, Jones DJL, Scott EN, Berry DP, Hemingway D, Miller A, Brown K, Gescher AJ, Steward WP (2013) Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration - a clinical pilot study including assessment of patient acceptability. Cancer Prev. Res. 6, 2119-2128.
• Karmokar A, Marczylo TH, Cai H, Steward WP, Gescher AJ, Brown K (2012) Dietary intake of rosmarinic acid by Apc^Min mice, a model of colorectal carcinogenesis: Levels of parent agent in the target tissue and effect on adenoma development. Mol. Nutr. Food Res. 56, 775-783.
• Patel KR, Brown VA, Jones DJL, Britton RG, Hemingway D, Miller A, West K, Booth T, Perloff M, Crowell J, Brenner D, Steward WP, Gescher AJ, Brown K (2010) Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res.70, 7392-7399.
• Brown VA, Patel K, Viskaduraki M, Crowell J, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher AJ, Brenner DE (2010) Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: Safety, pharmacokinetics and effect on the insulin-like growth factor axis. Cancer Res. 70, 9003-9011.

Reviews on cancer prevention

• Forman D, Bauld L, Bonanni B, Brenner H, Brown K, Dillner J, Kampmann E, Manczuk M, Riboli E, Steindorf K, Storm H, Garcia CE, Wild CP. (2018) Time for a European initiative for research to prevent cancer. A manifesto for Cancer Prevention Europe (CPE). Journal of Cancer Policy 17, 15–23.
• Serrano D, Bonanni B, Brown K. (2019) Therapeutic Cancer Prevention: achievements and ongoing challenges. A focus on Breast and Colorectal cancer. Mol. Oncol. 13, 579-590.
• Wild CP, Espina C, Bauld L, Bonanni B, Brenner H, Brown K, Dillner J, Forman D Kampman E, Nilbert M, Steindorf K, Storm H, Vineis P, Baumann M, Schüz J. (2019) Cancer Prevention Europe. Mol. Oncol. 13, 528-534.
• Brown K, Rufini A (2015) New concepts and challenges in the clinical translation of cancer preventive therapies: the role of pharmacodynamic biomarkers. eCancer 9 601.
• Steward WP, Brown K (2013) Cancer Chemoprevention – a rapidly evolving field. Br. J. Cancer 109, 1-7.

Reviews on resveratrol

• Brown K, Aburido G, Britton RG (2020) Resveratrol for cancer prevention: current gaps and opportunities. In: Pezzuto J., Vang O. (eds) Natural Products for Cancer Chemoprevention. Springer, Cham. https://doi.org/10.1007/978-3-030-39855-2_2
• Britton RG, Kovoor C, Brown K (2015) Direct molecular targets of resveratrol: Identifying key interactions to unlock complex mechanisms. Ann. N. Y. Acad. Sci. 1348, 124-133.
• Gescher A, Steward WP, Brown K (2013) Resveratrol in the management of human cancer – how strong is the clinical evidence? Ann. N. Y. Acad. Sci. Vol 1290 12-20. (Eds Vang O. & Brown K.)
• Brown K, Vang O Editors of Resveratrol and health. 2^nd International Scientific Conference on Resveratrol and Health. (2013) Ann. N. Y. Acad. Sci. 1290.
• Vang O, Ahmad N, Baile CA, Baur JA, Brown K, Csiszar A, Das DK, Delmas D, Gottfried C, Lin H-Y, Ma Q-Y, Mukhopadhyay P, Nalini N, Pezzuto JM, Richard T, Shukla Y, Surh Y-J, Szekeres T, Szkudelski T, Walle T, Wu JM(2011) What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS ONE 6, e19881.
• Scott E, Steward WP, Gescher AJ, Brown K (2011) Resveratrol in human cancer chemoprevention – choosing the “right” dose. Molecular Nutrition & Food Research 56, 7–13.

DNA damage and carcinogenesis

• Pottenger LH, Boysen G, Brown K, Cadet J, Fuchs RP, Johnson GE, Swenberg JA. (2018) Understanding the Importance of the Ethylene Oxide- and Propylene Oxide-induced DNA Adducts and Mutations in Risk Assessment: Insights from 15 years of Research. Environ. Mol. Mutagen. 60, 100-121.
• Marsden DA, Jones DJL, Britton RG, Ognibene T, Ubick E, Farmer PB, Brown K (2009) Dose response relationships for N7-(2-hydroxyethyl)guanine induced by low dose [¹⁴C]-ethylene oxide: evidence for a novel mechanism of endogenous DNA adduct formation. Cancer Res.69, 3052-3059.
• Tompkins EM, Jones DJL, McLuckie KIE, Farmer PB, Brown K (2009) Weak mutagenicity of DNA adducts derived from ethylene oxide exposure. Mutat. Res.: Genet. Toxicol. Environ. Mutagen. 678, 129-137.
• Tompkins EM, Jones DJL, Lamb JH, Marsden DA, Farmer PB, Brown K (2008) Simultaneous detection of five different 2-hydroxyethyl DNA adducts formed by ethylene oxide exposure, using a high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry assay. Rapid Commun. Mass Spectrom 22, 19-28.
• Brown K, Tompkins EM, Boocock DJ, Martin EA, Farmer PB, Turteltaub KW, Ubick E, Hemingway D, Horner-Glister E, White INH (2007) Tamoxifen forms DNA adducts in human colon after administration of a single [¹⁴C]-labeled therapeutic dose. Cancer Res. 67, 6995-7002.
• Martin EA, Brown K, Gaskell M, Al-Azzawi F, Garner RC, Boocock DJ, Mattock E, Pring DW, Dingley K, Turteltaub KW, Smith LL, White INH (2003) Tamoxifen DNA damage detected in human endometrium using accelerator mass spectrometry. Cancer Res., 63, 8461-8465.
• Brown K, Hingerty BE, Guenther EA, Krishnan VV, Broyde S, Turteltaub KW, Cosman M (2001) Solution structure of the 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine C8-deoxyguanosine adduct in duplex DNA. Proceedings of the National Academy of Science, USA 98, 8507-8512.

Karen has previously supervised 22 students to successful award of their PhD, including clinical fellows and numerous international students from a range of countries.  

She is currently the primary supervisor for three PhD students who are conducting projects on colorectal cancer and mesothelioma prevention. 

Karen would welcome enquiries from self-funded students looking to conduct research in the area of cancer prevention.

Karen is co-convenor of the MSc in Cancer Molecular Pathology and Therapeutics and module lead for MB7403 (Cancer Therapeutics)

She is also contributes to teaching on the following modules:

• Natural Sciences Foundation Course, NT0001 Principles of Biological Science
• BS3003 Cancer Cell and Molecular Biology
• BS20092 Molecular Cell Biology
• CB06 Biology and therapy of cancer

Interview with Turi King: https://citizen.le.ac.uk/podcast/developing-therapies-to-prevent-cancer/ 

Resveratrol

Use of drugs or dietary constituents for cancer prevention