WIMM PI
Curriculum Vitae
Personal Data
Name
Nationality
Email
Adrian L Harris
UK
adrian.harris@oncology.ox.ac.uk
Present Position
Since 1988
Cancer Research UK Professor of Medical Oncology, University of Oxford
Director of Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine
Consultant Medical Oncologist, Oxford University Hospitals NHS Trust
Professorial Fellow of St Hugh's College, University of Oxford
Experimental Cancer Medicine Centre Director, Oxford Radcliffe Hospitals NHS Trust and Cancer
Research UK until 2010
Chairman of Cancer Research UK Cancer Centre, Oxford
Previous Positions
1973
House Physician to Professor D A Price-Evans and Dr R B McConnell, Liverpool
Royal Infirmary
1974
House Surgeon to Professor R Shields and Mr A Cushieri
1974
Senior House Officer to Dr T Bailey, Dr B Walker, Dr G Honey, Broadgreen Hospital
(Diabetes, Cardiology, Geriatrics).
1975
Medical Registrar and Clinical Scientist (MRC Training Fellowship) in University
Department of Clinical Pharmacology and Nuffield Department of Medicine, Oxford
(Prof. D.G. Grahame-Smith, Prof D J Weatherall) (Clinical Pharmacology,
Haematological Oncology, General Medicine)
1978
Medical Registrar in the Academic Department of Medicine, Royal Free Hospital
London (Professor S Sherlock, Professor N McIntyre, Dr D Jewell, Dr I M James)
(General Medicine, Gastroenterology, Clinical Pharmacology)
1979
Senior Medical Registrar, Royal Marsden Hospital, Fulham Road, London (Dr I E
Smith, Dr E Wiltshaw). Lecturer, Institute of Cancer Research (Medical Oncology)
1981
Visiting research worker, Mutagenesis Laboratory, Imperial Cancer Research Fund,
London (Dr T Lindahl)
1982
Professor of Clinical Oncology, University of Newcastle, Newcastle upon Tyne.
Director, Cancer Research Unit, Royal Victoria Infirmary
1990
Deputy Director Clinical Research Imperial Cancer Research Fund
1
Research Achievements
I have worked on the mechanisms of tumour angiogenesis and the adaption to hypoxia induced by
antiangiogenic therapy. I first demonstrating that blood vessels were upregulated in breast
cancers with poor prognosis, regardless of every other factor, and that they were growing fifty
times more rapidly than normal endothelial cells in adjacent breast tissues. I elucidated the main
angiogenic pathways involved, particularly showing for the first time that VEGF was upregulated
and associated with poor outcome, this provided the basic clinical observation and biology link to
develop anti-VEGF therapy. I continued to investigate mechanisms of tumour angiogenesis
demonstrating that a novel notch ligand, cloned by us and other groups simultaneously, delta-like
4, was highly upregulated in breast cancer and many other tumour types associated with
aggressive outcome and resulted in differentiated well-perfused vasculature in xenograft models.
We showed that it was associated with a resistance to antiangiogenic therapy with anti-VEGF and
that blocking delta-like 4 could markedly synergise with anti-VEGF therapy.
I investigated the signalling pathways by which delta-like 4 regulated tumour endothelium and
showed that it regulated several previously unrecognised pathways important for angiogenesis,
including a sulphatase that regulates individual cell heparin-binding in an autocrine role and, the
regulation of ELTD1 which is a major focus of current work, as it has no defined signalling pathway
currently, is extracellular and therapeutically has shown dramatic effects in xenograft models when
it is inhibited by intravenous siRNA targeting mouse vasculature.
As part of the understanding of how tumours adapt to hypoxia and antiangiogenic therapy we have
investigated several major metabolic pathways which have culminated in therapeutic advances,
particularly the first demonstration that an extracellular carbonic anhydrase CA9 was upregulated
in response to HIF signalling, that it is the most upregulated gene in the HIF repertoire, it can be
targeted and has substantial anti-tumour effects when combined with antiangiogenic therapy and
that it regulates pH in an unexpected manner.
These studies have been continued to investigate other hypoxia regulated pathways, where we
demonstrated for the first time a glycogen shunt is critical for tumour cell growth, preventing
senescence and protecting from free-radicals. Future studies are involved in following the
metabolic fate of metabolites such glutamine, glutathione, glucose and their interactions with
hypoxia regulated pathway in vivo.
Additional angiogenic pathways were discovered related to exosome secretion and distant
targeting of notch-signalling and we are currently investigating the key oncogene that really
regulates the release of these exosomes, how targeting it could affect tumour angiogenesis. This is
linked to clinic studies measuring these in patient blood and tumour.
What are the Future Aims of Your Current Group?
Background
Tumours require angiogenesis to grow and metastasise. Vascular endothelial growth factor
(VEGF) is one of the key angiogenic factors, regulated by hypoxia, and it is effective for treating
several types of cancer. However, resistance is common both de novo and after initial response to
therapy. This implies different mechanisms of angiogenesis are important initially, and adaptation
to the environmental stresses, including hypoxia, induced by the anti-angiogenic therapy.
Specific aims of the research
To investigate the role of notch signalling in tumour angiogenesis and in resistance to anti-VEGF
therapy.
To investigate the survival pathways in tumour and stroma produced by hypoxia in response to
inhibition of notch and VEGF signalling.
To investigate changes in metabolic and mitochondrial pathways induced by hypoxia and the their
role in tumour survival and as therapeutic targets
2
To discover new angiogenic pathways, that allow the bypass of current angiogenic pathways, and
to develop these into therapies, which will help provide new approaches to anti-angiogenic therapy
We investigate a fundamental aspect of tumor biology, tumor angiogenesis, a mechanism which
tumors require to grow, invade, metastasise and support growth of metastases at distant sites. We
aim to discover new pathways involved in tumor angiogenesis that are targetable, either because
they use a signalling pathway or they are on the cell surface.
We contributed to this through discovery that the endothelial expressed delta-like 4 [Dll4] was
selectively upregulated in tumor endothelium, evaluating its role and its expression in human
cancers and analysis of a phase I study using a therapeutic antibody to Dll4. Additionally to notch
signalling by Dll4 we have shown Jagged 1 is also involved and with a grant from the CRUK
[shared with Prof A Banham], have developed a therapeutic antibody program making blocking
antibodies. We have also discovered a cell surface protein, ELTD1, is highly upregulated in tumor
angiogenesis and involved in early sprouting, and shows a substantial effect in blocking tumor
growth in several tumor types, far more effective than chemotherapy. We are using bioinformatic
approaches and dissection and sequencing of human tumour endothelium to discover new
mechanisms.
Additionally, trying to predict which patients respond to antiangiogenic therapies is important
because of cost-effectiveness of expensive therapies and being able to offer patients additional
therapies upfront. We have investigated this extensively in breast cancer patients treated with
bevacizumab, using advanced imaging methods, and C13 metabolism studies in patients and their
tumours, and serial tumour samples for genetic analysis. We discovered three major patterns of
response: one of resistance, which is probably mediated with the Dll4 pathway; one of sensitivity,
and one where the blood vessels respond but the tumor does not, probably because of metabolic
adaptation.
This has driven our research further into the mechanisms of which tumors survive hypoxia. This
includes analysis of the hypoxia response pathways in tumour cells and endothelium, involving
miRNA, LNC RNA, antisense RNA and epigenetic modulation. For the metabolic response, we are
particularly focusing on metabolic changes involving lipid metabolism. This has involved
developing Mass spectrometry and NMR assays and flux analyses. We have found that lipid
metabolism is extensively modulated by pathways under hypoxia which are not dependant on HIF,
a major new finding and also that there is a glycogen shunt that is critical for the pentose
phosphate shunt to function. These pathways are highly targetable and we are able to evaluate the
relevance clinically through studies in patients and tumour biopsies, as well as access to extensive
tissue microarrays with long-term prognosis to assess the relevance.
Through collaboration with the Targeted Drug Discovery Institute we are able to screen for the
relevant targets and take these further forward.
How do these Aims Contribute to the Understanding and/or Management of Human Disease
Understanding new pathways of tumour angiogenesis and how they relate to resistance to current
therapies will provide new targets for therapy. Understanding how cancer cells adjust to a high
stress hypoxic environment, gives us the opportunity to use synthetic lethal approaches for
therapy, which should have low normal tissue toxicity. Our studies therefore help personalise
medicine to select patients for expensive therapies to optimise their treatment, to use dynamic
monitoring therapy with imaging biopsies to select patients to overcome early resistance, to
understand resistance mechanisms and develop new therapeutic approaches which would use
synthetic lethality interactions based on these pathways.
Lay Summary of Research
3
We aim to develop ways to improve the treatment of breast cancer and other tumour types, by
blocking the blood supply to tumors. Tumors cannot grow without a new blood supply developing
from pre-existing blood vessels. This is called angiogenesis. We showed that human tumor
endothelial cells (those cells that line the blood vessels) are growing fifty times more rapidly than
normal ones and thus provide a new target for therapy. Several drugs are available that block the
major substance made by cancers, that stimulate these endothelial cells (called vascular
endothelial growth factor, VEGF) but this is expensive and only works in a sub- group of patients.
We want to make our basic discoveries on the mechanisms of growth of blood vessels, how they
are stimulated by cancers, new pathways that can grow independently of VEGF, and translate this
into clinical relevance. Thus we have extensive interactions with a pathology team, and conduct
clinical trials investigating these pathways in breast cancer, offering patients new drugs if they have
resistant cancers, in phase I and phase II trials. This is closely integrated with new developments
in imaging that pick up metabolism changes in cancers and blood flow and many other biomarkers.
We have found a signalling pathway called delta-like 4 is critical, and other new pathways called
ELTD1 and SULF1 are important and are developing drugs to block them, again helped by strong
links in Oxford with the Chemistry Department.
Our patient investigations have shown that some tumors change their metabolism on treatment
with anti-angiogenic drugs, so that they can survive under low-oxygen conditions and poor nutrient
supply. This is very important because it is a major difference between tumor and normal cells.
Tumors often have a low oxygen concentration because they use it up in growing rapidly and also
because the blood supply, although growing rapidly, is often insufficient to meet the demands of
growth. We are developing techniques to measure these changes in metabolism directly in
patient’s cancers and are conducting experiments in vitro, with cancer cell lines under low oxygen
conditions to see how these changes help the cells survive. Detailed studies using specially
labelled nutrient precursors will be able to track the fate of these, both in patients and in their
tumors. Discovering the pathways involved has shown fat metabolism is important and this is now
being translated into a clinical study. We are re-positioning drugs that were used to block the fat
metabolism in diabetes to try and treat cancer and stop cancer cells using some of the same
pathways. Thus the understanding of the basic biology of metabolism, hypoxia and how this relates
to the blood supply of tumors is yielding many new insights and ways of treating cancer.
4
Ten Key Publications Throughout your Career
1.
Horak, E. R., Leek, R., Klenk, N., Lejeune, S., Smith, K., Stuart, N., Greenall, M., Stepniewska,
K., and Harris, A. L. (1992) Angiogenesis, Assessed by Platelet Endothelial-Cell Adhesion
Molecule Antibodies, as Indicator of Node Metastases and Survival in Breast-Cancer, Lancet
340, 1120-1124.
2. Fox, S. B., Gatter, K. C., Bicknell, R., Going, J. J., Stanton, P., Cooke, T. G., and Harris, A. L.
(1993) Relationship of Endothelial-Cell Proliferation to Tumor Vascularity in Human BreastCancer, Cancer Research 53, 4161-4163.
3. Dachs, G. U., Patterson, A. V., Firth, J. D., Ratcliffe, P. J., M. S., Stratford, I. J., and Harris, A. L.
(1997) Targeting gene expression to hypoxic tumor cells, Nature Medicine 3, 515-520.
4. Relf, M., LeJeune, S., Scott, P. A. E., Fox, S., Smith, K., Leek, R., Moghaddam, A., Whitehouse,
R., Bicknell, R., and Harris, A. L. (1997) Expression of the angiogenic factors vascular
endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in
human primary breast cancer and its relation to angiogenesis, Cancer Research 57, 963-969.
5. Wykoff, C. C., Beasley, N. J. P., Watson, P. H., Turner, K. J., Pastorek, J., Sibtain, A., Wilson,
G. D., Turley, H., Talks, K. L., Maxwell, P. H., Pugh, C. W., Ratcliffe, P. J., and Harris, A. L.
(2000) Hypoxia-inducible expression of tumor-associated carbonic anhydrases, Cancer
Research 60, 7075-7083.
6. Sheldon, H., Heikamp, E., Turley, H., Dragovic, R., Thomas, P., Oon, C. E., Leek, R.,
Edelmann, M., Kessler, B., Sainson, R. C., Sargent, I., Li, J. L., and Harris, A. L. (2010) New
mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into
exosomes, Blood 116, 2385-2394.
7. Liu, S. K., Bham, S. A., Fokas, E., Beech, J., Im, J., Cho, S., Harris, A. L.,* and Muschel, R. J.*
(2011 Epub ahead of print 18 October - DOI: 10.1093/jnci/djr419) Delta-Like Ligand 4-Notch
Blockade and Tumor Radiation Response, J Natl Cancer Inst. * equal senior author
8. Favaro, E., Bensaad, K., Chong, M. G., Tennant, D. A., Ferguson, D. J., Snell, C., Steers, G.,
Turley, H., Li, J. L., Gunther, U. L., Buffa, F. M., McIntyre, A., and Harris, A. L. (2012) Glucose
Utilization via Glycogen Phosphorylase Sustains Proliferation and Prevents Premature
Senescence in Cancer Cells, Cell Metabolism.
9. Masiero, M., Simoes, F.C., Han, H.D., Snell, C., Peterkin, T., Bridges, E., Mangala, L.S., Wu,
S.Y., Pradeep, S., Li, D., Han, C., Dalton, H., Lopez-Berestein, G., Tuynman, J.B., Mortensen,
N., Li, J.L., Patient, R., Sood, A.K., Banham, A.H., Harris, A.L., and Buffa, F.M. (2013). A Core
Human Primary Tumor Angiogenesis Signature Identifies the Endothelial Orphan Receptor
ELTD1 as a Key Regulator of Angiogenesis. Cancer Cell 24, 229-241.
10. Behjati, S., Tarpey, P.S., Sheldon, H. and other, Stratton, M.R., Futreal, P.A., Flanagan, A.M.,
Harris, A., and Campbell, P.J. (2014). Recurrent PTPRB and PLCG1 mutations in
angiosarcoma. Nat Genet 46, 376-379.
All Publications Over the Past 6 Years 2008 - 2014
H score overall
152
H score last 5 years
No of citations to my work overall
No of citations to my work last 5 years
92,000
38,000
582 articles have had at least 10 citations in the last 5 years [Google Scholar].
I am a Highly Cited Researcher 2014, as classified by Thompson Reuters and included in their
‘2014 World’s most Influential Scientific Minds.’
Derived from InCites Essential Science Indicators, a subset of the Web of Science, Highly Cited
Researchers presents more than 3,000 authors in 21 main fields of science and the social sciences.
5
These researchers earned the distinction by writing the greatest numbers of reports officially
designated by Essential Science Indicators as Highly Cited Papers—ranking among the top 1%
most cited for their subject field and year of publication—between 2002 and 2012. Thus, the listings
of Highly Cited Researchers feature authors whose published work in their specialty areas has
consistently been judged by peers to be of particular significance and utility. There are only 30 UK
clinicians with this designation.
2014
1. Agorreta, J., Hu, J., Liu, D., Delia, D., Turley, H., Ferguson, D.J., Iborra, F., Pajares, M.J.,
Larrayoz, M., Zudaire, I., Pio, R., Montuenga, L.M., Harris, A.L., Gatter, K., and Pezzella, F.
(2014). TRAP1 Regulates Proliferation, Mitochondrial Function and has Prognostic
Significance in NSCLC. Mol Cancer Res.
2. Airley, R.E., McHugh, P., Evans, A.R., Harris, B., Winchester, L., Buffa, F.M., Al-Tameemi, W.,
Leek, R., and Harris, A.L. (2014). Role of carbohydrate response element-binding protein
(ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression. Br
J Cancer 110, 715-723.
3. Behjati, S., Tarpey, P.S., Sheldon, H., Martincorena, I., Van Loo, P., Gundem, G., Wedge,
D.C., Ramakrishna, M., Cooke, S.L., Pillay, N., Vollan, H.K., Papaemmanuil, E., Koss, H.,
Bunney, T.D., Hardy, C., Joseph, O.R., Martin, S., Mudie, L., Butler, A., Teague, J.W., Patil,
M., Steers, G., Cao, Y., Gumbs, C., Ingram, D., Lazar, A.J., Little, L., Mahadeshwar, H.,
Protopopov, A., Al Sannaa, G.A., Seth, S., Song, X., Tang, J., Zhang, J., Ravi, V., Torres, K.E.,
Khatri, B., Halai, D., Roxanis, I., Baumhoer, D., Tirabosco, R., Amary, M.F., Boshoff, C.,
McDermott, U., Katan, M., Stratton, M.R., Futreal, P.A., Flanagan, A.M., Harris, A., and
Campbell, P.J. (2014). Recurrent PTPRB and PLCG1 mutations in angiosarcoma. Nat Genet
46, 376-379.
4. Bensaad, K., and Harris, A.L. (2014). Hypoxia and metabolism in cancer. Adv Exp Med Biol
772, 1-39.
5. Camps, C., Saini, H.K., Mole, D.R., Choudhry, H., Reczko, M., Guerra-Assuncao, J.A., Tian,
Y.M., Buffa, F.M., Harris, A.L., Hatzigeorgiou, A.G., Enright, A.J., and Ragoussis, J. (2014).
Integrated analysis of microRNA and mRNA expression and association with HIF binding
reveals the complexity of microRNA expression regulation under hypoxia. Mol Cancer 13, 28.
6. Choudhry, H., Schodel, J., Oikonomopoulos, S., Camps, C., Grampp, S., Harris, A.L., Ratcliffe,
P.J., Ragoussis, J., and Mole, D.R. (2014). Extensive regulation of the non-coding
transcriptome by hypoxia: role of HIF in releasing paused RNApol2. EMBO Rep 15, 70-76.
7. Favara, D.M., and Harris, A.L. (2014). VEGF sticky-trap: the first report of a non-systemically
acting angiogenesis inhibitor. EMBO Mol Med 6, 577-579.
8. Feldinger, K., Generali, D., Kramer-Marek, G., Gijsen, M., Ng, T.B., Wong, J.H., Strina, C.,
Cappelletti, M., Andreis, D., Li, J.L., Bridges, E., Turley, H., Leek, R., Roxanis, I., Capala, J.,
Murphy, G., Harris, A.L., and Kong, A. (2014). ADAM10 mediates trastuzumab resistance and
is correlated with survival in HER2 positive breast cancer. Oncotarget.
9. Generali, D., Buffa, F.M., Deb, S., Cummings, M., Reid, L.E., Taylor, M., Andreis, D., Allevi, G.,
Ferrero, G., Byrne, D., Martinotti, M., Bottini, A., Harris, A.L., Lakhani, S.R., and Fox, S.B.
(2014). COX-2 expression is predictive for early relapse and aromatase inhibitor resistance in
patients with ductal carcinoma in situ of the breast, and is a target for treatment. Br J Cancer.
10. Gorsi, B., Liu, F., Ma, X., Chico, T.J., v, A., Kramer, K.L., Bridges, E., Monteiro, R., Harris, A.L.,
Patient, R., and Stringer, S.E. (2014). The heparan sulfate editing enzyme Sulf1 plays a novel
role in zebrafish VegfA mediated arterial venous identity. Angiogenesis 17, 77-91.
11. Harjes, U., Bridges, E., McIntyre, A., Fielding, B.A., and Harris, A.L. (2014). Fatty acid binding
protein 4, a point of convergence for angiogenic and metabolic signalling pathways in
endothelial cells. J Biol Chem.
12. Interiano, R.B., Yang, J., Harris, A.L., and Davidoff, A.M. (2014). Seven In Absentia Homolog 2
(SIAH2) downregulation is associated with tamoxifen resistance in MCF-7 breast cancer cells.
J Surg Res.
13. Jiang, H., Favaro, E., Goulbourne, C.N., Rakowska, P.D., Hughes, G.M., Ryadnov, M.G.,
Fong, L.G., Young, S.G., Ferguson, D.J., Harris, A.L., and Grovenor, C.R. (2014). Stable
isotope imaging of biological samples with high resolution secondary ion mass spectrometry
and complementary techniques. Methods.
6
14. Koukourakis, M.I., Giatromanolaki, A., Bottini, A., Cappelletti, M.R., Zanotti, L., Allevi, G.,
Strina, C., Ardine, M., Milani, M., Brugnoli, G., Martinotti, M., Ferrero, G., Bertoni, R., Ferrozzi,
F., Harris, A.L., and Generali, D. (2014). Prospective neoadjuvant analysis of PET imaging and
mechanisms of resistance to Trastuzumab shows role of HIF1 and autophagy. Br J Cancer
110, 2209-2216.
15. Leithner, K., Hrzenjak, A., Trotzmuller, M., Moustafa, T., Kofeler, H.C., Wohlkoenig, C.,
Stacher, E., Lindenmann, J., Harris, A.L., Olschewski, A., and Olschewski, H. (2014). PCK2
activation mediates an adaptive response to glucose depletion in lung cancer. Oncogene.
16. Nafi, S., Generali, D., Kramer-Marek, G., Gijsen, M., Strina, C., Cappelletti, M., Andreis, D.,
Haider, S., Li, J.L., Bridges, E., Capala, J., Ioannis, R., Harris, A.L., and Kong, A. (2014).
Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor
outcome in HER2 positive breast cancer. Oncotarget.
17. Newey, S.E., Tsaknakis, G., Khoo, C.P., Athanassopoulos, T., Camicia, R., Zhang, Y.,
Grabowska, R., Harris, A.L., Roubelakis, M.G., and Watt, S.M. (2014). The Hematopoietic
Chemokine CXCL12 Promotes Integration of Human Endothelial Colony Forming Cell-Derived
Cells into Immature Vessel Networks. Stem Cells Dev.
18. Pezzella, F., and Harris, A.L. (2014). When cancer co-opts the vasculature. N Engl J Med 370,
2146-2147.
19. Snell, C.E., Turley, H., McIntyre, A., Li, D., Masiero, M., Schofield, C.J., Gatter, K.C., Harris,
A.L., and Pezzella, F. (2014). Proline-hydroxylated hypoxia-inducible factor 1alpha (HIF1alpha) upregulation in human tumours. PLoS One 9, e88955.
20. Swietach, P., Vaughan-Jones, R.D., Harris, A.L., and Hulikova, A. (2014). The chemistry,
physiology and pathology of pH in cancer. Philos Trans R Soc Lond B Biol Sci 369, 20130099.
2013
1. Allevi, G., Strina, C., Andreis, D., Zanoni, V., Bazzola, L., Bonardi, S., Foroni, C., Milani, M.,
Cappelletti, M.R., Gussago, F., Aguggini, S., Giardini, R., Martinotti, M., Fox, S.B., Harris, A.L.,
Bottini, A., Berruti, A., and Generali, D. (2013). Increased pathological complete response rate
after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or
progesterone receptor-positive breast cancer. Br J Cancer 108, 1587-1592.
2. Betts, G.N., Eustace, A., Patiar, S., Valentine, H.R., Irlam, J., Ramachandran, A., Merve, A.,
Homer, J.J., Moller-Levet, C., Buffa, F.M., Hall, G., Miller, C.J., Harris, A.L., and West, C.M.
(2013). Prospective technical validation and assessment of intra-tumour heterogeneity of a low
density array hypoxia gene profile in head and neck squamous cell carcinoma. Eur J Cancer
49, 156-165.
3. Blick, C., Ramachandran, A., Wigfield, S., McCormick, R., Jubb, A., Buffa, F.M., Turley, H.,
Knowles, M.A., Cranston, D., Catto, J., and Harris, A.L. (2013). Hypoxia regulates FGFR3
expression via HIF-1alpha and miR-100 and contributes to cell survival in non-muscle invasive
bladder cancer. Br J Cancer 109, 50-59.
4. Donnem, T., Hu, J., Ferguson, M., Adighibe, O., Snell, C., Harris, A.L., Gatter, K.C., and
Pezzella, F. (2013). Vessel co-option in primary human tumors and metastases: an obstacle to
effective anti-angiogenic treatment? Cancer Med 2, 427-436.
5. Eustace, A., Irlam, J.J., Taylor, J., Denley, H., Agrawal, S., Choudhury, A., Ryder, D., Ord,
J.J., Harris, A.L., Rojas, A.M., Hoskin, P.J., and West, C.M. (2013). Necrosis predicts benefit
from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III
randomised trial. Radiother Oncol 108, 40-47.
6. Eustace, A., Mani, N., Span, P.N., Irlam, J.J., Taylor, J., Betts, G.N., Denley, H., Miller, C.J.,
Homer, J.J., Rojas, A.M., Hoskin, P.J., Buffa, F.M., Harris, A.L., Kaanders, J.H., and West,
C.M. (2013). A 26-Gene Hypoxia Signature Predicts Benefit from Hypoxia-Modifying Therapy
in Laryngeal Cancer but Not Bladder Cancer. Clin Cancer Res 19, 4879-4888.
7. Favaro, E., and Harris, A.L. (2013). Targeting glycogen metabolism: a novel strategy to inhibit
cancer cell growth? Oncotarget 4, 3-4.
8. Giatromanolaki, A., Koukourakis, M.I., Koutsopoulos, A.V., Harris, A.L., Gatter, K., and
Sivridis, E. (2013). Autophagy and hypoxia in colonic adenomas related to aggressive
features. Colorectal Dis 15, e223-230.
9. Giatromanolaki, A., Koukourakis, M.I., Pouliliou, S., Gatter, K.C., Pezzella, F., Harris, A.L., and
Sivridis, E. (2013). Overexpression of LC3A autophagy protein in follicular and diffuse large B7
cell lymphomas. Hematol Oncol Stem Cell Ther 6, 20-25.
10. Gieling, R.G., Parker, C.A., De Costa, L.A., Robertson, N., Harris, A.L., Stratford, I.J., and
Williams, K.J. (2013). Inhibition of carbonic anhydrase activity modifies the toxicity of
doxorubicin and melphalan in tumour cells in vitro. J Enzyme Inhib Med Chem 28, 360-369.
11. Gorsi, B., Liu, F., Ma, X., Chico, T.J., Shrinivasan, A., Kramer, K.L., Bridges, E., Monteiro, R.,
Harris, A.L., Patient, R., and Stringer, S.E. (2013). The heparan sulfate editing enzyme Sulf1
plays a novel role in zebrafish VegfA mediated arterial venous identity. Angiogenesis 1, 77-91.
12. Griffiths, B., Lewis, C.A., Bensaad, K., Ros, S., Zhang, Q., Ferber, E.C., Konisti, S., Peck, B.,
Miess, H., East, P., Wakelam, M., Harris, A.L., and Schulze, A. (2013). Sterol regulatory
element binding protein-dependent regulation of lipid synthesis supports cell survival and
tumor growth. Cancer Metab 1, 3.
13. Harris, A.L. (2013). Breast screening remains a controversial issue. Br J Cancer 108, 2197.
14. Horsley, L., Cummings, J., Middleton, M., Ward, T., Backen, A., Clamp, A., Dawson, M.,
Farmer, H., Fisher, N., Halbert, G., Halford, S., Harris, A., Hasan, J., Hogg, P., Kumaran, G.,
Little, R., Parker, G.J., Potter, P., Saunders, M., Roberts, C., Shaw, D., Smith, N., Smythe, J.,
Taylor, A., Turner, H., Watson, Y., Dive, C., and Jayson, G.C. (2013). A phase 1 trial of
intravenous 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) in patients with
advanced solid tumours. Cancer Chemother Pharmacol 72, 1343-1352.
15. Hulikova, A., Harris, A.L., Vaughan-Jones, R.D., and Swietach, P. (2013). Regulation of
intracellular pH in cancer cell lines under normoxia and hypoxia. J Cell Physiol 228, 743-752.
16. Koukourakis, M.I., Giatromanolaki, A., Sivridis, E., Gatter, K.C., and Harris, A.L. (2013). High
DLL4 expression in tumour-associated vessels predicts for favorable radiotherapy outcome in
locally advanced squamous cell head-neck cancer (HNSCC). Angiogenesis 16, 343-351.
17. Kumar, K., Wigfield, S., Gee, H.E., Devlin, C.M., Singleton, D., Li, J.L., Buffa, F., Huffman, M.,
Sinn, A.L., Silver, J., Turley, H., Leek, R., Harris, A.L., and Ivan, M. (2013). Dichloroacetate
reverses the hypoxic adaptation to bevacizumab and enhances its antitumor effects in mouse
xenografts. J Mol Med (Berl) 91, 749-758.
18. Masiero, M., Simoes, F.C., Han, H.D., Snell, C., Peterkin, T., Bridges, E., Mangala, L.S., Wu,
S.Y., Pradeep, S., Li, D., Han, C., Dalton, H., Lopez-Berestein, G., Tuynman, J.B., Mortensen,
N., Li, J.L., Patient, R., Sood, A.K., Banham, A.H., Harris, A.L., and Buffa, F.M. (2013). A Core
Human Primary Tumor Angiogenesis Signature Identifies the Endothelial Orphan Receptor
ELTD1 as a Key Regulator of Angiogenesis. Cancer Cell 24, 229-241.
19. McCormick, R.I., Blick, C., Ragoussis, J., Schoedel, J., Mole, D.R., Young, A.C., Selby, P.J.,
Banks, R.E., and Harris, A.L. (2013). miR-210 is a target of hypoxia-inducible factors 1 and 2
in renal cancer, regulates ISCU and correlates with good prognosis. Br J Cancer 108, 11331142.
20. Nikitenko, L.L., Leek, R., Henderson, S., Pillay, N., Turley, H., Generali, D., Gunningham, S.,
Morrin, H.R., Pellagatti, A., Rees, M.C., Harris, A., and Fox, S.B. (2013). The G-protein
Coupled Receptor CLR is Up-regulated in an Autocrine Loop with Adrenomedullin in Clear Cell
Renal Cell Carcinoma and Associated with Poor Prognosis. Clin Cancer Res 19, 5740-5748.
21. Ong, C.C., Jubb, A.M., Jakubiak, D., Zhou, W., Rudolph, J., Haverty, P.M., Kowanetz, M.,
Yan, Y., Tremayne, J., Lisle, R., Harris, A.L., Friedman, L.S., Belvin, M., Middleton, M.R.,
Blackwood, E.M., Koeppen, H., and Hoeflich, K.P. (2013). P21-Activated Kinase 1 (PAK1) as
a Therapeutic Target in BRAF Wild-Type Melanoma. J Natl Cancer Inst 105, 606-607.
22. Pike, L.R., Singleton, D.C., Buffa, F., Abramczyk, O., Phadwal, K., Li, J.L., Simon, A.K.,
Murray, J.T., and Harris, A.L. (2013). Transcriptional up-regulation of ULK1 by ATF4
contributes to cancer cell survival. Biochem J 449, 389-400.
23. Ramachandran, A., Betts, G., Bhana, S., Helme, G., Blick, C., Moller-Levet, C., Saunders, E.,
Valentine, H., Pepper, S., Miller, C.J., Buffa, F., Harris, A.L., and West, C.M. (2013). An in vivo
hypoxia metagene identifies the novel hypoxia inducible factor target gene SLCO1B3. Eur J
Cancer 49, 1741-1751.
24. Singleton, D.C., and Harris, A.L. (2013). Microenvironmental induced essentiality of
autophagy. Clin Cancer Res 19, 2791-2793.
25. Ward, C., Langdon, S.P., Mullen, P., Harris, A.L., Harrison, D.J., Supuran, C.T., and Kunkler,
I.H. (2013). New strategies for targeting the hypoxic tumour microenvironment in breast
cancer. Cancer Treat Rev 39, 171-179.
26.
8
27. Whiteman, P., de Madrid, B.H., Taylor, P., Li, D., Heslop, R., Viticheep, N., Tan, J.Z., Shimizu,
H., Callaghan, J., Masiero, M., Li, J.L., Banham, A.H., Harris, A.L., Lea, S.M., Redfield, C.,
Baron, M., and Handford, P.A. (2013). Molecular basis for jagged-1/serrate ligand recognition
by the notch receptor. J Biol Chem 288, 7305-7312.
2012
1. Athanassopoulos, A., Tsaknakis, G., Newey, S. E., Harris, A. L., Kean, J., Tyler, M. P., and
Watt, S. M. (2012) Microvessel networks in pre-formed in artificial clinical grade dermal
substitutes in vitro using cells from haematopoietic tissues, Burns : journal of the International
Society for Burn Injuries 38, 691-701.
2. Betts, G. N., Eustace, A., Patiar, S., Valentine, H. R., Irlam, J., Ramachandran, A., Merve, A.,
Homer, J. J., Moller-Levet, C., Buffa, F. M., Hall, G., Miller, C. J., Harris, A. L., and West, C. M.
(2012) Prospective technical validation and assessment of intra-tumour heterogeneity of a low
density array hypoxia gene profile in head and neck squamous cell carcinoma, European
journal of cancer (Oxford, England : 1990).
3. Biswas, S., Charlesworth, P. J., Turner, G. D., Leek, R., Thamboo, P. T., Campo, L., Turley,
H., Dildey, P., Protheroe, A., Cranston, D., Gatter, K. C., Pezzella, F., and Harris, A. L. (2012)
CD31 angiogenesis and combined expression of HIF-1alpha and HIF-2alpha are prognostic in
primary clear-cell renal cell carcinoma (CC-RCC), but HIFalpha transcriptional products are
not: implications for antiangiogenic trials and HIFalpha biomarker studies in primary CC-RCC,
Carcinogenesis.
4. Cavazzoni, A., Bonelli, M. A., Fumarola, C., La Monica, S., Airoud, K., Bertoni, R., Alfieri, R. R.,
Galetti, M., Tramonti, S., Galvani, E., Harris, A. L., Martin, L. A., Andreis, D., Bottini, A.,
Generali, D., and Petronini, P. G. (2012) Overcoming acquired resistance to letrozole by
targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones, Cancer letters 323, 77-87.
5. Favaro, E., Bensaad, K., Chong, M. G., Tennant, D. A., Ferguson, D. J., Snell, C., Steers, G.,
Turley, H., Li, J. L., Gunther, U. L., Buffa, F. M., McIntyre, A., and Harris, A. L. (2012) Glucose
Utilization via Glycogen Phosphorylase Sustains Proliferation and Prevents Premature
Senescence in Cancer Cells, Cell Metabolism.
6. Giatromanolaki, A., Koukourakis, M. I., Sivridis, E., Gatter, K. C., Trarbach, T., Folprecht, G.,
Shi, M. M., Lebwohl, D., Jalava, T., Laurent, D., Meinhardt, G., and Harris, A. L. (2012) Vascular
density analysis in colorectal cancer patients treated with vatalanib (PTK787/ZK222584) in the
randomised CONFIRM trials, British journal of cancer.
7. Giatromanolaki, A., Sivridis, E., Bechrakis, N. E., Willerding, G., St Charitoudis, G., Foerster, M.
H., Gatter, K. C., Harris, A. L., and Koukourakis, M. I. (2012) Phosphorylated pVEGFR2/KDR
receptor expression in uveal melanomas: relation with HIF2alpha and survival, Clinical &
experimental metastasis 29, 11-17.
8. Gieling, R. G., Parker, C. A., De Costa, L. A., Robertson, N., Harris, A. L., Stratford, I. J., and
Williams, K. J. (2012) Inhibition of carbonic anhydrase activity modifies the toxicity of
doxorubicin and melphalan in tumour cells in vitro, Journal of enzyme inhibition and medicinal
chemistry.
9. Harjes, U., Bensaad, K., and Harris, A. L. (2012) Endothelial cell metabolism and implications
for cancer therapy, British journal of cancer 107, 1207-1212.
10. Harris, A. L. (2012) Metabolic compartments in tumor tissue: implications for therapy, Cell Cycle
11, 13-14.
11. Hulikova, A., Harris, A. L., Vaughan-Jones, R. D., and Swietach, P. (2012) Acid-extrusion from
tissue: the interplay between membrane transporters and pH buffers, Current pharmaceutical
design 18, 1331-1337.
12. Hulikova, A., Harris, A. L., Vaughan-Jones, R. D., and Swietach, P. (2012) Regulation of
intracellular pH in cancer cell lines under normoxia and hypoxia, Journal of cellular physiology.
13. Jones, D. T., and Harris, A. L. (2012) Small-molecule inhibitors of the HIF pathway and
synthetic lethal interactions, Expert opinion on therapeutic targets.
9
14. Jones, D. T., Lechertier, T., Mitter, R., Herbert, J. M., Bicknell, R., Jones, J. L., Li, J. L., Buffa,
F., Harris, A. L., and Hodivala-Dilke, K. (2012) Gene expression analysis in human breast
cancer associated blood vessels, PloS one 7, e44294.
15. Jubb, A. M., Browning, L., Campo, L., Turley, H., Steers, G., Thurston, G., Harris, A. L., and
Ansorge, O. (2012) Expression of vascular Notch ligands Delta-like 4 and Jagged-1 in
glioblastoma, Histopathology 60, 740-747.
16. Khan, O. A., Blann, A. D., Payne, M. J., Middleton, M. R., Protheroe, A. S., Talbot, D. C., Taylor,
M., Han, C., Patil, M., and Harris, A. L. (2012) Reply: Metronomic chemotherapy with
cyclophosphamide and dexamethasone in patients with metastatic carcinoma of the prostate,
British journal of cancer.
17. Klionsky, D., R., et.al.(2012) Guidelines for the use and interpretation of assays for monitoring
autophagy, Autophagy 8, 445-544.
18. Koukourakis, M. I., Giatromanolaki, A., Sivridis, E., Gatter, K. C., and Harris, A. L. (2012) High
DLL4 expression in tumour-associated vessels predicts for favorable radiotherapy outcome in
locally advanced squamous cell head-neck cancer (HNSCC), Angiogenesis.
19. McIntyre, A., Patiar, S., Wigfield, S., Li, J. L., Ledaki, I., Turley, H., Leek, R., Snell, C., Gatter,
K., Sly, W. S., Vaughan-Jones, R. D., Swietach, P., and Harris, A. L. (2012) Carbonic
Anhydrase IX Promotes Tumor Growth and Necrosis In Vivo and Inhibition Enhances AntiVEGF Therapy, Clinical cancer research : an official journal of the American Association for
Cancer Research 18, 3100-3111.
20. Nathan, P., Zweifel, M., Padhani, A. R., Koh, D. M., Ng, M., Collins, D. J., Harris, A., Carden, C.,
Smythe, J., Fisher, N., Taylor, N. J., Stirling, J. J., Lu, S. P., Leach, M. O., Rustin, G. J., and
Judson, I. (2012) Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with
Bevacizumab in Patients with Advanced Cancer, Clinical cancer research : an official journal of
the American Association for Cancer Research 18, 3428-3439.
21. Patel, N., Harris, A. L., Gleeson, F. V., and Vallis, K. A. (2012) Clinical imaging of tumor
angiogenesis, Future oncology (London, England) 8, 1443-1459.
22. Pike, L. R., Phadwal, K., Simon, A. K., and Harris, A. L. (2012) ATF4 orchestrates a program of
BH3-only protein expression in severe hypoxia, Molecular biology reports 39, 10811-10822.
23. Pike, L. R., Singleton, D. C., Buffa, F., Abramczyk, O., Phadwal, K., Li, J. L., Simon, A. K.,
Murray, J. T., and Harris, A. L. (2012) Transcriptional upregulation of ULK1 by ATF4 contributes
to cancer cell survival, The Biochemical journal.
24. Pinhel, I., Hills, M., Drury, S., Salter, J., Sumo, G., A'Hern, R., Bliss, J. M., Sestak, I., Cuzick, J.,
Barrett-Lee, P., Harris, A., and Dowsett, M. (2012) ER and HER2 expression are positively
correlated in HER2 non-overexpressing breast cancer, Breast cancer research : BCR 14, R46.
25. Schulze, A., and Harris, A. L. (2012) How cancer metabolism is tuned for proliferation and
vulnerable to disruption, Nature 491, 364-373.
26. Singleton, D. C., and Harris, A. L. (2012) Targeting the ATF4 pathway in cancer therapy, Expert
opinion on therapeutic targets.
27. Swietach, P., Hulikova, A., Patiar, S., Vaughan-Jones, R. D., and Harris, A. L. (2012)
Importance of intracellular pH in determining the uptake and efficacy of the weakly basic
chemotherapeutic drug, doxorubicin, PloS one 7, e35949.
28. Ward, C., Langdon, S. P., Mullen, P., Harris, A. L., Harrison, D. J., Supuran, C. T., and Kunkler,
I. H. (2012) New strategies for targeting the hypoxic tumour microenvironment in breast cancer,
Cancer treatment reviews.
29. Yang, J., Staples, O., Thomas, L. W., Briston, T., Robson, M., Poon, E., Simoes, M. L., El-Emir,
E., Buffa, F. M., Ahmed, A., Annear, N. P., Shukla, D., Pedley, B. R., Maxwell, P. H., Harris, A.
L., and Ashcroft, M. (2012) Human CHCHD4 mitochondrial proteins regulate cellular oxygen
consumption rate and metabolism and provide a critical role in hypoxia signaling and tumor
progression, The Journal of clinical investigation 122, 600-611.
10
2011
1. Bardella C, El-Bahrawy M, Frizzell N, Adam J, Ternette N, Hatipoglu E, et al. Aberrant
succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust
biomarker of mutation status. J Pathol 2011; 225:4-11.
2. Berruti A, Generali D, Kaufmann M, Puztai L, Curigliano G, Aglietta M, et al. International
expert consensus on primary systemic therapy in the management of early breast cancer:
highlights of the fourth symposium on primary systemic therapy in the management of
operable breast cancer, cremona, Italy (2010). J Natl Cancer Inst Monogr 2011; 2011:147-51.
3. Bridges E, Oon CE, Harris A. Notch regulation of tumor angiogenesis. Future Oncol 2011;
7:569-88.
4. Bridges EM, Harris AL. The angiogenic process as a therapeutic target in cancer. Biochem
Pharmacol 2011; 81:1183-91.
5. Buffa FM, Camps C, Winchester L, Snell CE, Gee HE, Sheldon H, et al. microRNA-Associated
Progression Pathways and Potential Therapeutic Targets Identified by Integrated mRNA and
microRNA Expression Profiling in Breast Cancer. Cancer Res 2011; 71:5635-45.
6. Campbell HE, Epstein D, Bloomfield D, Griffin S, Manca A, Yarnold J, et al. The costeffectiveness of adjuvant chemotherapy for early breast cancer: A comparison of no
chemotherapy and first, second, and third generation regimens for patients with differing
prognoses. Eur J Cancer 2011
Epub ahead of print 12 July - DOI:
http://dx.doi.org/10.1016/j.ejca.2011.06.019; 47 2517-30.
7. Church DN, Phillips BR, Stuckey DJ, Barnes DJ, Buffa FM, Manek S, et al. Igf2 ligand
dependency of Pten(+/-) developmental and tumour phenotypes in the mouse. Oncogene
2011.
8. Coutts AS, Pires IM, Weston L, Buffa FM, Milani M, Li JL, et al. Hypoxia-driven cell motility
reflects the interplay between JMY and HIF-1alpha. Oncogene 2011 Epub ahead of print 30
May - DOI: 10.1038/onc.2011.188.
9. Dragovic RA, Gardiner C, Brooks AS, Tannetta DS, Ferguson DJ, Hole P, et al. Sizing and
phenotyping of cellulars vesicles using Nanoparticle Tracking Analysis. Nanomedicine 2011
Epub ahead of print 4 May - DOI: 10.1016/j.nano.2011.04.003.
10. Dubois L, Peeters S, Lieuwes NG, Geusens N, Thiry A, Wigfield S, et al. Specific inhibition of
carbonic anhydrase IX activity enhances the in vivo therapeutic effect of tumor irradiation.
Radiother Oncol 2011; 99:424-31.
11. Favaro E, Lord S, Harris AL, Buffa FM. Gene expression and hypoxia in breast cancer.
Genome Med 2011; 3:55.
12. Fox SB, Generali D, Berruti A, Brizzi MP, Campo L, Bonardi S, et al. The prolyl hydroxylase
enzymes are positively associated with hypoxia-inducible factor-1alpha and vascular
endothelial growth factor in human breast cancer and alter in response to primary systemic
treatment with epirubicin and tamoxifen. Breast Cancer Res 2011; 13:R16.
13. Gee HE, Buffa FM, Camps C, Ramachandran A, Leek R, Taylor M, et al. The small-nucleolar
RNAs commonly used for microRNA normalisation correlate with tumour pathology and
prognosis. Br J Cancer 2011; 104:1168-77.
14. Generali D, Berruti A, Foroni C, Bazzola L, Andreis D, Allevi G, et al. Molecular oncology and
the neoadjuvant setting: the perfect blend for treatment personalization and clinical trial
design. J Natl Cancer Inst Monogr 2011; 2011:67-70.
15. Ghazoui Z, Buffa FM, Dunbier AK, Anderson H, Dexter T, Detre S, et al. Close and stable
relationship between proliferation and a hypoxia metagene in aromatase inhibitor-treated ERpositive breast cancer. Clin Cancer Res 2011; 17:3005-12.
16. Giatromanolaki A, Sivridis E, Bechrakis NE, Willerding G, St Charitoudis G, Foerster MH, et al.
Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with
HIF2alpha and survival. Clin Exp Metastasis 2011.
17. Golinska M, Troy H, Chung YL, McSheehy PM, Mayr M, Yin X, et al. Adaptation to HIF-1
deficiency by upregulation of the AMP/ATP ratio and phosphofructokinase activation in
hepatomas. BMC Cancer 2011; 11:198.
11
18. Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial
assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscleinvasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011;
29:2171-7.
19. Horak J, White J, Harris AL, Verrill M, Carmichael J, Holt A, et al. The effect of different
etiologies of hepatic impairment on the pharmacokinetics of gefitinib. Cancer Chemother
Pharmacol 2011 Epub ahead of print 13 April - DOI: 10.1007/s00280-011-1611-2.
20. Jubb AM, Browning L, Campo L, Turley H, Steers G, Thurston G, et al. Expression of vascular
Notch ligands Delta-like 4 and Jagged-1 in glioblastoma. Histopathology 2012.
21. Jubb AM, Miller KD, Rugo HS, Harris AL, Chen D, Reimann JD, et al. Impact of exploratory
biomarkers on the treatment effect of bevacizumab in metastatic breast cancer. Clin Cancer
Res 2011; 17:372-81.
22. Khan OA, Blann AD, Payne MJ, Middleton MR, Protheroe AS, Talbot DC, et al. Continuous
low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with
advanced cancer. Br J Cancer 2011; 104:1822-7.
23. Koperek O, Bergner O, Pichlhofer B, Oberndorfer F, Hainfellner JA, Kaserer K, et al.
Expression of hypoxia-associated proteins in sporadic medullary thyroid cancer is associated
with desmoplastic stroma reaction and lymph node metastasis and may indicate somatic
mutations in the VHL gene. J Pathol 2011; 225:63-72.
24. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celia-Terrassa T, et al. Direct targeting of
Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization.
Nat Med 2011; 17:1101-8.
25. Koukourakis MI, Giatromanolaki A, Sivridis E, Gatter KC, Trarbach T, Folprecht G, et al.
Prognostic and predictive role of lactate dehydrogenase 5 expression in colorectal cancer
patients treated with PTK787/ZK 222584 (vatalanib) antiangiogenic therapy. Clin Cancer Res
2011; 17:4892-900.
26. Li JL, Sainson RC, Oon CE, Turley H, Leek R, Sheldon H, et al. DLL4-Notch Signaling
Mediates Tumor Resistance to Anti-VEGF Therapy In Vivo. Cancer Res 2011; 71:6073-83.
27. Liu SK, Bham SA, Fokas E, Beech J, Im J, Cho S, et al. Delta-Like Ligand 4-Notch Blockade
and Tumor Radiation Response. J Natl Cancer Inst 2011 Epub ahead of print 18 October DOI: 10.1093/jnci/djr419.
28. Mehta S, Hughes NP, Buffa FM, Li SP, Adams RF, Adwani A, et al. Assessing early
therapeutic response to bevacizumab in primary breast cancer using magnetic resonance
imaging and gene expression profiles. J Natl Cancer Inst Monogr 2011; 2011:71-4.
29. Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, et al. miR-182mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors.
Mol Cell 2011; 41:210-20.
30. Murri-Plesko MT, Hulikova A, Oosterwijk E, Scott AM, Zortea A, Harris AL, et al. Antibody
inhibiting enzymatic activity of tumour-associated carbonic anhydrase isoform IX. Eur J
Pharmacol 2011; 657:173-83.
31. Ong CC, Jubb AM, Haverty PM, Zhou W, Tran V, Truong T, et al. Targeting p21-activated
kinase 1 (PAK1) to induce apoptosis of tumor cells. Proc Natl Acad Sci U S A 2011; 108:717782.
32. Ong CC, Jubb AM, Zhou W, Haverty PM, Harris AL, Belvin M, et al. p21-activated kinase 1:
PAK'ed with potential. Oncotarget 2011; 2:491-6.
33. Oon CE, Harris AL. New pathways and mechanisms regulating and responding to Delta-like
ligand 4-Notch signalling in tumour angiogenesis. Biochem Soc Trans 2011; 39:1612-8.
34. Rothe F, Ignatiadis M, Chaboteaux C, Haibe-Kains B, Kheddoumi N, Majjaj S, et al. Global
MicroRNA Expression Profiling Identifies MiR-210 Associated with Tumor Proliferation,
Invasion and Poor Clinical Outcome in Breast Cancer. PLoS One 2011; 6:e20980.
35. Rzymski T, Petry A, Kracun D, Riess F, Pike L, Harris AL, et al. The unfolded protein response
controls induction and activation of ADAM17/TACE by severe hypoxia and ER stress.
Oncogene 2011.
12
36. Serafin V, Persano L, Moserle L, Esposito G, Ghisi M, Curtarello M, et al. Notch3 signalling
promotes tumour growth in colorectal cancer. J Pathol 2011; 224:448-60.
37. Shaida N, Chan P, Turley H, Jones CM, Kanga S, Ritchie RW, et al. Nuclear localization of
factor inhibitor hypoxia-inducible factor in prostate cancer is associated with poor prognosis. J
Urol 2011; 185:1513-8.
38. Yan M, Jene N, Byrne D, Millar EK, O'Toole SA, McNeil CM, et al. Recruitment of regulatory T
cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor
prognosis in basal-like breast cancers. Breast Cancer Res 2011; 13:R47.
2010
1. Ameri K, Luong R, Zhang H, Powell AA, Montgomery KD, Espinosa I, et al. Circulating tumour
cells demonstrate an altered response to hypoxia and an aggressive phenotype. British journal
of cancer 2010; 102:561-9.
2. Azam F, Mehta S, Harris AL. Mechanisms of resistance to antiangiogenesis therapy. Eur J
Cancer 2010; 46:1323-32.
3. Biswas S, Troy H, Leek R, Chung YL, Li JL, Raval RR, et al. Effects of HIF-1alpha and
HIF2alpha on Growth and Metabolism of Clear-Cell Renal Cell Carcinoma 786-0 Xenografts. J
Oncol 2010; 2010:757908.
4. Bonelli MA, Fumarola C, Alfieri RR, La Monica S, Cavazzoni A, Galetti M, et al. Synergistic
activity of letrozole and sorafenib on breast cancer cells. Breast cancer research and treatment
2010; 124:79-88.
5. Buffa FM, Harris AL, West CM, Miller CJ. Large meta-analysis of multiple cancers reveals a
common, compact and highly prognostic hypoxia metagene. British journal of cancer 2010;
102:428-35.
6. Campbell HE, Gray AM, Harris AL, Briggs AH, Taylor MA. Estimation and external validation of
a new prognostic model for predicting recurrence-free survival for early breast cancer patients
in the UK. British journal of cancer 2010; 103:776-86.
7. Chen L, Zeng X, Wang J, Briggs SS, O'Neill E, Li J, et al. Roles of tetrahydrobiopterin in
promoting tumor angiogenesis. Am J Pathol 2010; 177:2671-80.
8. da Silva RG, Tavora B, Robinson SD, Reynolds LE, Szekeres C, Lamar J, et al. Endothelial
alpha3beta1-integrin represses pathological angiogenesis and sustains endothelial-VEGF. Am
J Pathol 2010; 177:1534-48.
9. Dangoor A, Lorigan P, Keilholz U, Schadendorf D, Harris A, Ottensmeier C, et al. Clinical and
immunological responses in metastatic melanoma patients vaccinated with a high-dose polyepitope vaccine. Cancer Immunol Immunother 2010; 59:863-73.
10. Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, et al. MicroRNA210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells
by targeting iron sulfur cluster protein ISCU. PLoS One 2010; 5:e10345.
11. Gee HE, Camps C, Buffa FM, Patiar S, Winter SC, Betts G, et al. hsa-mir-210 is a marker of
tumor hypoxia and a prognostic factor in head and neck cancer. Cancer 2010; 116:2148-58.
12. Giatromanolaki A, Koukourakis MI, Harris AL, Polychronidis A, Gatter KC, Sivridis E.
Prognostic relevance of light chain 3 (LC3A) autophagy patterns in colorectal
adenocarcinomas. J Clin Pathol 2010; 63:867-72.
13. Gijsen M, King P, Perera T, Parker P, Larijani B, Harris A, et al. Upregulation of ADAM
proteases and HER ligands through a feedback loop mediates acquired resistance to
trastuzumab in HER2-amplified breast cancer. Breast Cancer Res 2010; 12 Suppl 1:O2.
14. Gijsen M, King P, Perera T, Parker PJ, Harris AL, Larijani B, et al. HER2 phosphorylation is
maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast
cancer. PLoS Biol 2010; 8:e1000563.
13
15. Gossage L, Zaitoun A, Fareed KR, Turley H, Aloysius M, Lobo DN, et al. Expression of key
hypoxia sensing prolyl-hydroxylases PHD1, -2 and -3 in pancreaticobiliary cancer.
Histopathology 2010; 56:908-20.
16. Grzmil M, Rzymski T, Milani M, Harris AL, Capper RG, Saunders NJ, et al. An oncogenic role
of eIF3e/INT6 in human breast cancer. Oncogene 2010; 29:4080-9.
17. Hannigan A, Smith P, Kalna G, Lo Nigro C, Orange C, O'Brien DI, et al. Epigenetic
downregulation of human disabled homolog 2 switches TGF-beta from a tumor suppressor to
a tumor promoter. J Clin Invest 2010; 120:2842-57.
18. Higgins GS, Harris AL, Prevo R, Helleday T, McKenna WG, Buffa FM. Overexpression Of
POLQ Confers a Poor Prognosis In Early Breast Cancer Patients. Oncotarget 2010; 1:175-84.
19. Issaeva N, Thomas HD, Djureinovic T, Jaspers JE, Stoimenov I, Kyle S, et al. 6-thioguanine
selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Cancer
research 2010; 70:6268-76.
20. Jubb AM, Buffa FM, Harris AL. Assessment of tumour hypoxia for prediction of response to
therapy and cancer prognosis. J Cell Mol Med 2010; 14:18-29.
21. Jubb AM, Harris AL. Biomarkers to predict the clinical efficacy of bevacizumab in cancer.
Lancet Oncol 2010; 11:1172-83.
22. Jubb AM, Soilleux EJ, Turley H, Steers G, Parker A, Low I, et al. Expression of vascular notch
ligand delta-like 4 and inflammatory markers in breast cancer. Am J Pathol 2010; 176:201928.
23. Koukourakis MI, Giatromanolaki A, Sivridis E, Pitiakoudis M, Gatter KC, Harris AL. Beclin 1
over- and underexpression in colorectal cancer: distinct patterns relate to prognosis and
tumour hypoxia. British journal of cancer 2010; 103:1209-14.
24. Lau KH, Christlieb M, Schroder M, Sheldon H, Harris AL, Grovenor CR. Development of a new
bimodal imaging methodology: a combination of fluorescence microscopy and high-resolution
secondary ion mass spectrometry. J Microsc 2010; 240:21-31.
25. Li JL, Jubb AM, Harris AL. Targeting DLL4 in tumors shows preclinical activity but potentially
significant toxicity. Future Oncol 2010; 6:1099-103.
26. Liu D, Hu J, Agorreta J, Cesario A, Zhang Y, Harris AL, et al. Tumor necrosis factor receptorassociated protein 1(TRAP1) regulates genes involved in cell cycle and metastases. Cancer
Lett 2010; 296:194-205.
27. Lord S, Harris AL. Angiogenesis - still a worthwhile target for breast cancer therapy? Breast
Cancer Res 2010; 12 Suppl 4:S19.
28. Martin SK, Diamond P, Williams SA, To LB, Peet DJ, Fujii N, et al. Hypoxia-inducible factor-2
is a novel regulator of aberrant CXCL12 expression in multiple myeloma plasma cells.
Haematologica 2010; 95:776-84.
29. McCormick R, Buffa FM, Ragoussis J, Harris AL. The role of hypoxia regulated microRNAs in
cancer. Curr Top Microbiol Immunol 2010; 345:47-70.
30. Mele T, Generali D, Fox S, Brizzi MP, Bersiga A, Milani M, et al. Anti-angiogenic effect of
tamoxifen combined with epirubicin in breast cancer patients. Breast cancer research and
treatment 2010; 123:795-804.
31. Mellor HR, Rouschop KM, Wigfield SM, Wouters BG, Harris AL. Synchronised phosphorylation
of BNIP3, Bcl-2 and Bcl-xL in response to microtubule-active drugs is JNK-independent and
requires a mitotic kinase. Biochem Pharmacol 2010; 79:1562-72.
32. Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, et al. miR-182Mediated Downregulation of BRCA1 Impacts DNA Repair and Sensitivity to PARP Inhibitors.
Mol Cell 2010; 41:210-20.
33. Pires IM, Bencokova Z, Milani M, Folkes LK, Li JL, Stratford MR, et al. Effects of acute versus
chronic hypoxia on DNA damage responses and genomic instability. Cancer research 2010;
70:925-35.
34. Rzymski T, Milani M, Pike L, Buffa F, Mellor HR, Winchester L, et al. Regulation of autophagy
by ATF4 in response to severe hypoxia. Oncogene 2010; 29:4424-35.
14
35. Sheldon H, Heikamp E, Turley H, Dragovic R, Thomas P, Oon CE, et al. New mechanism for
Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes.
Blood 2010; 116:2385-94.
36. Sivridis E, Koukourakis MI, Zois CE, Ledaki I, Ferguson DJ, Harris AL, et al. LC3A-positive
light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.
Am J Pathol 2010; 176:2477-89.
37. Swietach P, Hulikova A, Vaughan-Jones RD, Harris AL. New insights into the physiological
role of carbonic anhydrase IX in tumour pH regulation. Oncogene 2010; 29:6509-21.
38. Thurlow JK, Pena Murillo CL, Hunter KD, Buffa FM, Patiar S, Betts G, et al. Spectral clustering
of microarray data elucidates the roles of microenvironment remodeling and immune
responses in survival of head and neck squamous cell carcinoma. J Clin Oncol 2010; 28:28818.
39. Watt SM, Athanassopoulos A, Harris AL, Tsaknakis G. Human endothelial stem/progenitor
cells, angiogenic factors and vascular repair. J R Soc Interface 2010; 7 Suppl 6:S731-51.
40. Yang J, Jubb AM, Pike L, Buffa FM, Turley H, Baban D, et al. The histone demethylase
JMJD2B is regulated by estrogen receptor alpha and hypoxia, and is a key mediator of
estrogen induced growth. Cancer research 2010; 70:6456-66.
41. Yau C, Mouradov D, Jorissen RN, Colella S, Mirza G, Steers G, et al. A statistical approach for
detecting genomic aberrations in heterogeneous tumor samples from single nucleotide
polymorphism genotyping data. Genome Biol 2010; 11:R92.
Markers of Esteem
1986
1994
1995
1998
2000
2004
2004
2005
2005
2009
2010
2012
Goulstonian Lecturer, Royal College of Physicians
St Lukes Lecture and Medal, Royal Academy of Medicine in Ireland
Daniel E Bergsagel Visiting Professorship, Ontario Cancer Institute, Toronto, Canada
Founder member of Academy of Medical Sciences
Link Lectureship Award Institute of Cancer Research
Henrietta Banting Prize for Breast Cancer Research,Toronto
Awarded Honorary Doctorate University of Thrace, Greece
Editor-in-Chief of British Journal of Cancer
Member of Editorial Board of Cancer Cell
Member of Board of Institute of Cancer Research, London
Chairman of Science Review Committee for Breakthrough Breast Cancer
NIHR Senior Investigator Award
Medical Research Council Clinical Fellowships Grants
(2004 - )
Member European Academy of Sciences Governing Body
(2010 - )
Founder Member of European Research Institute for Integrated Cellular Pathology (ERI-ICP)
(2010 - )
Garvin Institute Scientific Advisory Council, Sydney
(2010 - )
Member of Breast Cancer Campaign's Tissue Bank Tissue Access Committee (2010 - )
Cancer Research UK Stratified Medicine Scientific Advisory Board
(2010 - )
External Scientific Advisor to Center of Excellence in Genomic Medicine Research (CEGMR), King
Abdulaziz University, Jeddah (2009 - 2011)
Current Grant Support
Wellcome Trust
European Union METOXIA
Cancer Research UK (Notch Signalling)
Cancer Research UK (OCIC)
Cancer Research UK Oxford Centre
Cancer Research UK (Antibody Therapeutics)
Cancer Research UK (Medicinal Chemistry)
2009-2012
2009-2014
2010-2015
2008-2013
2010-2013
2009-2014
2009-2015
15
£322.913
£487,500
£3,162,000
£1,231,000
£4,514,000
£2,708,000
£292,600