Dr Agnieszka Michael

Senior Lecturer

Qualifications: MD PhD

Phone: Work: 01483 68 8546
Room no: 29 PGM 02

Office hours

1pm-5pm Mon

1pm-5pm Wed

Further information


Dr Agnieszka Michael MRCP PhD was appointed Clinical Senior Lecturer and Consultant Medical Oncologist at University of Surrey and Royal Surrey County Hospital in 2008. She has a specialist interest in ovarian and urological cancers as well as immunotherapy trials.
Dr Michael qualified in medicine at University of Wroclaw and undertook general medical and oncology training in UK, at the St George’s Hospital in London , Royal Marsden Hospital and Guy’s and St Thomas’ Hospital. In 2006 she was awarded a PhD for research in cancer immunotherapy and completed Specialist Training in Medical Oncology in 2007. Throughout her training and current post Dr Michael has worked in the cancer clinical trials' field, including early phase studies with novel immunotherapy agents, gene therapy and cancer vaccines as well as international multi-centre phase III and IV studies, as a Chief investigator and a local principal investigator. Dr Michael is a divisional lead for cancer within Kent, Surrey and Sussex ‘Clinical Research Network and since 2015 has been working as a Medical Director for Surrey Clinical Trials Unit.  

Research Interests

Cancer Clinical Trials 

Ovarian Cancer, Kidney Cancer , Immunotherapy 


Journal articles

  • Schumacher F, Al Olama A, Berndt S, Benlloch S, Ahmed M, Saunders E, Dadaev T, Leongamornlert D, Anokian E, Cieza-Borrella C, Goh C, Brook M, Sheng X, Fachal L, Dennis J, Tyrer J, Muir K, Lophatananon A, Stevens V, Gapstur S, Carter B, Tangen C, Goodman P, Thompson I, Batra J, Chambers S, Moya L, Clements J, Horvath L, Tilley W, Risbridger G, Gronberg H, Aly M, Nordström T, Pharoah P, Pashayan N, Schleutker J, Tammela T, Sipeky C, Auvinen A, Albanes D, Weinstein S, Wolk A, Håkansson N, West C, Dunning A, Burnet N, Mucci L, Giovannucci E, Andriole G, Cussenot O, Cancel-Tassin G, Koutros S, Beane Freeman L, Sorensen K, Orntoft T, Borre M, Maehle L, Grindedal E, Neal D, Donovan J, Hamdy F, Martin R, Travis R, Key T, Hamilton R, Fleshner N, Finelli A, Ingles S, Stern M, Rosenstein B, Kerns S, Ostrer H, Lu Y, Zhang H, Feng N, Mao X, Guo X, Wang G, Sun Z, Giles G, Southey M, MacInnis R, FitzGerald L, Kibel A, Drake B, Vega A, Gómez-Caamaño A, Szulkin R, Eklund M, Kogevinas M, Llorca J, Castaño-Vinyals G, Penney K, Stampfer M, Park J, Sellers T, Lin H, Stanford J, Cybulski C, Wokolorczyk D, Lubinski J, Ostrander E, Geybels M, Nordestgaard B, Nielsen S, Weischer M, Bisbjerg R, Røder M, Iversen P, Brenner H, Cuk K, Holleczek B, Maier C, Luedeke M, Schnoeller T, Kim J, Logothetis C, John E, Teixeira M, Paulo P, Cardoso M, Neuhausen S, Steele L, Ding Y, De Ruyck K, De Meerleer G, Ost P, Razack A, Lim J, Teo S, Lin D, Newcomb L, Lessel D, Gamulin M, Kulis T, Kaneva R, Usmani N, Singhal S, Slavov C, Mitev V, Parliament M, Claessens F, Joniau S, Van den Broeck T, Larkin S, Townsend P, Aukim-Hastie C, Dominguez M, Castelao J, Martinez M, Roobol M, Jenster G, van Schaik R, Menegaux F, Truong T, Koudou Y, Xu J, Khaw K, Cannon-Albright L, Pandha H, Michael A, Thibodeau S, McDonnell S, Schaid D, Lindstrom S, Turman C, Ma J, Hunter D, Riboli E, Siddiq A, Canzian F, Kolonel L, Le Marchand L, Hoover R, Machiela M, Cui Z, Kraft P, Amos C, Conti D, Easton D, Wiklund F, Chanock S, Henderson B, Kote-Jarai Z, Haiman C, Eeles R. (2018) 'Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci'. Nature Genetics, 50 (7), pp. 928-936.


    Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P ˂ 5.0 × 10−8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10−9; G˃C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T˃G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa.

  • Seibert T, Fan C, Wang Y, Zuber V, Karunamuni R, Parsons J, Eeles R, Easton D, Kote-Jarai Z, Al Olama A, Garcia S, Muir K, Grönberg H, Wiklund F, Aly M, Schleutker J, Sipeky C, Tammela T, Nordestgaard B, Nielsen S, Weischer M, Bisbjerg R, Røder M, Iversen P, Key T, Travis R, Neal D, Donovan J, Hamdy F, Pharoah P, Pashayan N, Khaw K, Maier C, Vogel W, Luedeke M, Herkommer K, Kibel A, Cybulski C, Wokolorczyk D, Kluzniak W, Cannon-Albright L, Brenner H, Cuk K, Saum K, Park J, Sellers T, Slavov C, Kaneva R, Mitev V, Batra J, Clements J, Spurdle A, Teixeira M, Paulo P, Maia S, Pandha H, Michael A, Kierzek A, Karow D, Mills I, Andreassen O, Dale A. (2018) 'Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts'. BMJ, 360 Article number j5757


    Objectives: Prostate-specific-antigen (PSA) screening resulted in reduced prostate cancer (PCa) mortality in a large clinical trial, but due to many false positives and overdiagnosis of indolent disease, many guidelines do not endorse universal screening and instead recommend an individualized decision based on each patient’s risk. We sought to develop and validate a genetic tool to predict age of aggressive PCa onset and to guide decisions of whom to screen and at what age. Design: Genotype, PCa status, and age were analyzed to select single-nucleotide polymorphisms (SNPs) associated with PCa diagnosis. These SNPs were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (i.e., not eligible for surveillance per NCCN Guidelines; any of: Gleason score ≥7, stage T3-T4, PSA ≥10, nodal metastasis, distant metastasis). The resulting polygenic hazard score (PHS) is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and screening PSA data. PHS was calculated for these men to test prediction of PCa-free survival. Setting: Multiple, international PRACTICAL consortium member institutions. Participants: All PRACTICAL consortium participants of European ancestry with known age, PCa status, and quality-assured iCOGS array genotype data. Development dataset comprised 31,747 men. Validation dataset comprised 6,411 men. Main outcome measures: PHS prediction of age of onset of aggressive PCa in validation set. Results: In the independent validation set, PHS calculated from 54 SNPs was a highly significant predictor of age at diagnosis of aggressive PCa (z=11.2, p<10-16). When men in the validation set with high PHS (>98th percentile) were compared to those with average PHS (30th-70th percentile), the hazard ratio for aggressive PCa was 2.9. Conclusions:Polygenic hazard scores give personalized genetic risk estimates that predict for age of onset of aggressive PCa.

  • Kelly Z, Moller-Levet CS, McGrath S, Butler-Manuel S, Madhuri TK, Kierzek AM, Pandha HS, Morgan RGL, Michael A . (2016) 'The prognostic significance of specific HOX gene expression patterns in ovarian cancer'. International Journal of Cancer, 139 (7), pp. 1608-1617.


    OBJECTIVE: HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. METHODS: HOX gene expression was determined in ovarian cancer cell lines and primary EOCs, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one way ANOVA and t-tests, using statistical software R and GraphPad. RESULTS: 30 of the 39 HOX genes were overexpressed in high grade serous EOC compared to normal tissue, most significant being HOXA3, A9, B13 and C10. We detected a molecular HOX gene-signature that predicted poor outcome: overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer.CONCLUSIONS: HOX genes are highly dysregulated in ovarian cancer. High expression of HOXA13, B6, C13, D1 and D13 is predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum–resistant cancer represents a new therapeutic option that should be further developed and tested in clinical trials.

  • Crea F, Quagliata L, Michael A, Liu HH, Frumento P, Azad AA, Xue H, Pikor L, Watahiki A, Morant R, Eppenberger-Castori S, Wang Y, Parolia A, Lennox KA, Lam WL, Gleave M, Chi KN, Pandha H, Wang Y, Helgason CD. (2015) 'Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression'. MOLECULAR ONCOLOGY, 10 (5), pp. 693-703.
  • Szulkin R, Karlsson R, Whitington T, Aly M, Gronberg H, Eeles RA, Easton DF, Kote-Jarai Z, Al Olama AA, Benlloch S, Muir K, Giles GG, Southey MC, FitzGerald LM, Henderson BE, Schumacher FR, Haiman CA, Sipeky C, Tammela TLJ, Nordestgaard BG, Key TJ, Travis RC, Neal DE, Donovan JL, Hamdy FC, Pharoah PDP, Pashayan N, Khaw K-T, Stanford JL, Thibodeau SN, McDonnell SK, Schaid DJ, Maier C, Vogel W, Luedeke M, Herkommer K, Kibel AS, Cybulski C, Lubinski J, Kluzniak W, Cannon-Albright L, Brenner H, Herrmann V, Holleczek B, Park JY, Sellers TA, Lim H-Y, Slavov C, Kaneva RP, Mitev VI, Spurdle A, Teixeira MR, Paulo P, Maia S, Pandha H, Michael A, Kierzek A, Batra J, Clements JA, Albanes D, Andriole GL, Berndt SI, Chanock S, Gapstur SM, Giovannucci EL, Hunter DJ, Kraft P, Le Marchand L, Ma J, Mondul AM, Penney KL, Stampfer MJ, Stevens VL, Weinstein SJ, Trichopoulou A, Bueno-de-Mesquita BH, Tjonneland A, Cox DG, Maehle L, Schleutker J, Lindstroem S, Wiklund F. (2015) 'Genome-Wide Association Study of Prostate Cancer-Specific Survival'. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 24 (11), pp. 1796-1800.
  • Szulkin R, Whitington T, Eklund M, Aly M, Eeles RA, Easton D, Kote-Jarai Z, Al Olama AA, Benlloch S, Muir K, Giles GG, Southey MC, Fitzgerald LM, Henderson BE, Schumacher F, Haiman CA, Schleutker J, Wahlfors T, Tammela TLJ, Nordestgaard BG, Key TJ, Travis RC, Neal DE, Donovan JL, Hamdy FC, Pharoah P, Pashayan N, Khaw K-T, Stanford JL, Thibodeau SN, McDonnell SK, Schaid DJ, Maier C, Vogel W, Luedeke M, Herkommer K, Kibel AS, Cybulski C, Lubinski J, Kluzniak W, Cannon-Albright L, Brenner H, Butterbach K, Stegmaier C, Park JY, Sellers T, Lim H-Y, Slavov C, Kaneva R, Mitev V, Batra J, Clements JA, Spurdle A, Teixeira MR, Paulo P, Maia S, Pandha H, Michael A, Kierzek A, Gronberg H, Wiklund F. (2015) 'Prediction of Individual Genetic Risk to Prostate Cancer Using a Polygenic Score'. PROSTATE, 75 (13), pp. 1467-1474.
  • Amin Al Olama A, Dadaev T, Hazelett DJ, Li Q, Leongamornlert D, Saunders EJ, Stephens S, Cieza-Borrella C, Whitmore I, Benlloch Garcia S, Giles GG, Southey MC, Fitzgerald L, Gronberg H, Wiklund F, Aly M, Henderson BE, Schumacher F, Haiman CA, Schleutker J, Wahlfors T, Tammela TL, Nordestgaard BG, Key TJ, Travis RC, Neal DE, Donovan JL, Hamdy FC, Pharoah P, Pashayan N, Khaw KT, Stanford JL, Thibodeau SN, Mcdonnell SK, Schaid DJ, Maier C, Vogel W, Luedeke M, Herkommer K, Kibel AS, Cybulski C, Wokołorczyk D, Kluzniak W, Cannon-Albright L, Brenner H, Butterbach K, Arndt V, Park JY, Sellers T, Lin HY, Slavov C, Kaneva R, Mitev V, Batra J, Clements JA, Spurdle A, Teixeira MR, Paulo P, Maia S, Pandha H, Michael A, Kierzek A, Govindasami K, Guy M, Lophatonanon A, Muir K, Viñuela A, Brown AA, PRACTICAL Consortium, COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative, Australian Prostate Cancer BioResource, UK Genetic Prostate Cancer Study Collaborators, UK ProtecT Study Collaborators, Freedman M, Conti DV, Easton D, Coetzee GA, Eeles RA, Kote-Jarai Z. (2015) 'Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans.'. Hum Mol Genet, England: 24 (19), pp. 5589-5602.


    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.

  • Michael A, Coward J, Brown A, Barber N, Pandha H. (2015) 'The tolerability of sunitinib in elderly patients with metastatic renal cancer.'. Clin Oncol (R Coll Radiol), England: 27 (6), pp. 371-372.
  • McGrath SE, Michael A, Morgan R, Pandha H. (2015) 'EN2 in Prostate Cancer'. Advances in Clinical Chemistry,
    [ Status: Accepted ]


    © 2015 Elsevier Inc. Despite extensive efforts to identify a clinically useful diagnostic biomarker in prostate cancer, no new test has been approved by regulatory authorities. As a result, this unmet need has shifted to biomarkers that additionally indicate presence or absence of "significant" disease. EN2 is a homeodomain-containing transcription factor secreted by prostate cancer into the urine and can be detected by enzyme-linked immunoassay. EN2 may be an ideal biomarker because normal prostate tissue and benign prostatic hypertrophic cells do not secrete EN2. This review discusses the enormous potential of EN2 to address this unmet need and provide the urologist with a simple, inexpensive, and reliable prostate cancer biomarker.

  • Michael A, Kelly Z, Moller-Levet C, Pandha H, Morgan R. (2014) 'HOX GENE EXPRESSION IN OVARIAN CANCER'. ANTICANCER RESEARCH, 34 (10), pp. 6058-6059.
  • Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Røder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Wokołorczyk D, Kluźniak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, Ma J, Stampfer M, Penney KL, Mucci L, John EM, Ingles SA, Kittles RA, Murphy AB, Pandha H, Michael A, Kierzek AM, Blot W, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Wu SY, Hennis A, Kibel AS, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Batra J, Clements J, Spurdle A, Teixeira MR, Paulo P, Maia S, Slavov C, Kaneva R, Mitev V, Witte JS, Casey G, Gillanders EM, Seminara D, Riboli E, Hamdy FC, Coetzee GA, Li Q, Freedman ML, Hunter DJ, Muir K, Gronberg H, Neal DE, Southey M, Giles GG, Severi G, Breast and Prostate Cancer Cohort Consortium (BPC3), PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, COGS (Collaborative Oncological Gene-environment Study) Consortium, GAME-ON/ELLIPSE Consortium, Cook MB, Nakagawa H, Wiklund F, Kraft P, Chanock SJ, Henderson BE, Easton DF, Eeles RA, Haiman CA. (2014) 'A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.'. Nat Genet, United States: 46 (10), pp. 1103-1109.


    Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

  • Annels NE, Simpson GR, Denyer M, McGrath SE, Falgari G, Killick E, Eeles R, Stebbing J, Pchejetski D, Cutress R, Murray N, Michael A, Pandha H. (2014) 'Spontaneous antibodies against Engrailed-2 (EN2) protein in patients with prostate cancer.'. Clin Exp Immunol, England: 177 (2), pp. 428-438.


    We reported the expression of the homeodomain-containing transcription factor Engrailed-2 (EN2) in prostate cancer and showed that the presence of EN2 protein in the urine was highly predictive of prostate cancer. This study aimed to determine whether patients with prostate cancer have EN2 autoantibodies, what the prevalence of these antibodies is and whether they are associated with disease stage. The spontaneous immunoglobulin (Ig)G immune response against EN2 and for comparison the tumour antigen New York Esophageal Squamous Cell Carcinoma 1 (NY-ESO-1), were tested by enzyme-linked immunosorbent assay (ELISA) in three different cohorts of prostate cancer patients as well as a group of men genetically predisposed to prostate cancer. Thirty-two of 353 (9·1%) of the SUN cohort representing all stages of prostate cancer demonstrated EN2 IgG responses, 12 of 107 patients (11·2%) in the advanced prostate cancer patients showed responses, while only four of 121 patients (3·3%) with castrate-resistant prostate cancer showed EN2 autoantibodies. No significant responses were found in the predisposed group. Anti-EN2 IgG responses were significantly higher in patients with prostate cancer compared to healthy control males and similarly prevalent to anti-NY-ESO-1 responses. While EN2 autoantibodies are not a useful diagnostic or monitoring tool, EN2 immunogenicity provides the rationale to pursue studies using EN2 as an immunotherapeutic target.

  • Morgan R, Boxall A, Harrington KJ, Simpson GR, Michael A, Pandha HS. (2014) 'Targeting HOX transcription factors in prostate cancer.'. BMC Urol, England: 14


    BACKGROUND: The HOX genes are a family of transcription factors that help to determine cell and tissue identity during early development, and which are also over-expressed in a number of malignancies where they have been shown to promote cell proliferation and survival. The purpose of this study was to evaluate the expression of HOX genes in prostate cancer and to establish whether prostate cancer cells are sensitive to killing by HXR9, an inhibitor of HOX function. METHODS: HOX function was inhibited using the HXR9 peptide. HOX gene expression was assessed by RNA extraction from cells or tissues followed by quantitative PCR, and siRNA was used to block the expression of the HOX target gene, cFos. In vivo modelling involved a mouse flank tumour induced by inoculation with LNCaP cells. RESULTS: In this study we show that the expression of HOX genes in prostate tumours is greatly increased with respect to normal prostate tissue. Targeting the interaction between HOX proteins and their PBX cofactor induces apoptosis in the prostate cancer derived cell lines PC3, DU145 and LNCaP, through a mechanism that involves a rapid increase in the expression of cFos, an oncogenic transcription factor. Furthermore, disrupting HOX/PBX binding using the HXR9 antagonist blocks the growth of LNCaP tumours in a xenograft model over an extended period. CONCLUSION: Many HOX genes are highly over-expressed in prostate cancer, and prostate cancer cells are sensitive to killing by HXR9 both in vitro and in vivo. The HOX genes are therefore a potential therapeutic target in prostate cancer.

  • Michael A, Relph KL, Annels NE, Pandha HS. (2014) 'Prostate cancer vaccines.'. Expert Review of Vaccines, 12 (3), pp. 253-262.


    In 2010, the US FDA approved the first therapeutic cancer vaccine for the treatment of castration refractory prostate cancer - sipuleucel-T. Prostate cancer is an ideal model for cancer vaccine development based on the ready demonstration of humoral and cellular immunity to a range of cancer antigens as well as often slow progression which means that patients who are otherwise well may have a radiologically evaluable minor progression, after conventional treatment and can undergo vaccine therapy over sufficient periods of time, so as to allow the generation of a robust antitumor response. The association of prostate cancer with one of the few serum cancer biomarkers in general use has also allowed assessment of response and risk stratification of patients. In this review, we will examine key aspects of the evolution of prostate cancer vaccines, which provides an accurate prototype for other cancers, and the challenges we face.

  • McGrath SE, Michael A, Morgan R, Pandha H. (2013) 'EN2: a novel prostate cancer biomarker.'. Biomark Med, England: 7 (6), pp. 893-901.


    Extensive efforts to identify a clinically useful biomarker for the diagnosis of prostate cancer have resulted in important insights into the biology of the disease, but no new test has been approved by regulatory authorities. The unmet need has also shifted to identifying biomarkers that not only diagnose prostate cancer but also indicate whether the patient has 'significant' disease. EN2 is a homeobox-containing transcription factor secreted specifically by prostate cancers into urine, where it can be detected by a simple ELISA assay. A number of studies have demonstrated the enormous potential of EN2 to address this unmet need and provide the urologist with a simple, cheap and efficient prostate cancer biomarker.

  • Michael A, Pandha H. (2013) 'Presentation and symptomatology of prostate cancer'. , pp. 467-471.


    © 2013 Springer-Verlag London. All rights are reserved.Prostate cancer can present at any stage of the disease and very frequently does not cause any symptoms at all. Most cancers arise in the periphery of the prostate gland and cause symptoms only when they have grown to compress the urethra or invade the sphincter [1]. In recent years, more and more of prostate cancer patients from the western hemisphere are diagnosed at an earlier stage due to rising prevalence of prostate-specific antigen (PSA) testing [2]. A study by Cooperberg et al. analyzed trends in clinical presentation in 2,078 men diagnosed between 1989 and 2001. The proportion of patients with low-risk tumor characteristics rose from 29.8 % in 1989-1992 to 45.3 % in 1999-2001 [3]. Studies based on the Department of Defense Center for Prostate Disease (CPDR) found downward migration at higher stage [3]. The percentage of patients presenting with locally advanced (T3 to T4) disease fell from 19.2 % in 1988 to 4.4 % in 1998; rates of metastatic disease at diagnosis likewise declined from 14.1 % in 1988 to 3.3 % in 1998.

  • McGrath SE, Michael A, Pandha H, Morgan R. (2013) 'Engrailed homeobox transcription factors as potential markers and targets in cancer'. FEBS Letters, 587 (6), pp. 549-554.


    Engrailed (En) is a member of the homeobox gene family, which encodes a homeodomain-containing transcription factor that is essential during early development. The only known site of normal adult Engrailed protein (EN) expression is in the nervous system, and it has been implicated in the development of both young-onset Parkinson's disease as well as autism. Over-expression of EN has been linked to tumour development in adults, particularly in breast, prostate, melanoma and ovarian cancers, and there is a growing interest in its role as a diagnostic and prognostic biomarker. It is hoped that further work may confirm associations between En expression and therapy-resistant, poor prognosis cancers, similar to that identified with other homeobox gene profiles. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  • McGrath SE, Michael A, Pandha H, Morgan R. (2013) 'Engrailed homeobox transcription factors as potential markers and targets in cancer.'. FEBS Lett, Netherlands: 587 (6), pp. 549-554.


    Engrailed (En) is a member of the homeobox gene family, which encodes a homeodomain-containing transcription factor that is essential during early development. The only known site of normal adult Engrailed protein (EN) expression is in the nervous system, and it has been implicated in the development of both young-onset Parkinson's disease as well as autism. Over-expression of EN has been linked to tumour development in adults, particularly in breast, prostate, melanoma and ovarian cancers, and there is a growing interest in its role as a diagnostic and prognostic biomarker. It is hoped that further work may confirm associations between En expression and therapy-resistant, poor prognosis cancers, similar to that identified with other homeobox gene profiles.

  • Larbi E, Madhuri K, Essapen S, Butler-Manuel S, Tailor A, Michael A. (2013) 'The Effect of Age on First-line Chemotherapy for Epithelial Ovarian Cancer and Primary Peritoneal Carcinoma'. Clinical Oncology, 25 (1)
  • Larbi E, Madhuri K, Essapen S, Butler-Manuel S, Tailor A, Michael A. (2012) 'The Effect of Age on First-line Chemotherapy for Epithelial Ovarian Cancer and Primary Peritoneal Carcinoma'. Clinical Oncology,
  • Morgan R, Boxall A, Simpson G, Michael A, Pandha H, Harrington K, Gillett C. (2012) 'Targeting the HOX/PBX dimer in breast cancer'. Breast Cancer Research and Treatment, 136 (2), pp. 389-398.


    The HOX genes are a family of closely related transcription factors that help to define the identity of cells and tissues during embryonic development and which are also frequently deregulated in a number of malignancies, including breast cancer. While relatively little is known about the roles that individual HOX genes play in cancer, it is however clear that these roles can be both contradictory, with some members acting as oncogenes and some as tumor suppressors, and also redundant, with several genes essentially having the same function. Here, we have attempted to address this complexity using the HXR9 peptide to target the interaction between HOX proteins and PBX, a second transcription factor that serves as a common co-factor for many HOX proteins. We show that HXR9 causes apoptosis in a number of breast cancer-derived cell lines and that sensitivity to HXR9 is directly related to the averaged expression of HOX genes HOXB1 through to HOXB9, providing a potential biomarker to predict the sensitivity of breast tumors to HXR9 or its derivatives. Measuring the expression of HOX genes HOXB1-HOXB9 in primary tumors revealed that a subset of tumors show highly elevated expression indicating that these might be potentially very sensitive to killing by HXR9. Furthermore, we show that while HXR9 blocks the oncogenic activity of HOX genes, it does not affect the known tumor-suppressor properties of a subset of HOX genes in breast cancer.

  • McGrath S, Madhuri TK, Susarla S, Haagsma B, Saleh F, Michael A. (2012) 'Low grade serous ovarian carcinoma with metastases to the sternum and ribs.'. Pathology, England: 44 (5), pp. 481-482.
  • Chen SS, Michael A, Butler-Manuel SA. (2012) 'Advances in the treatment of ovarian cancer: a potential role of antiinflammatory phytochemicals.'. Discov Med, United States: 13 (68), pp. 7-17.


    Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies worldwide. The five-year survival rates for stage IIIC and IV patients are 29% and 13%, respectively. Type-2 EOC cells have been found to be associated with this late stage disease. In contrast, women diagnosed in stage 1 disease, which mostly exhibits type-1 cells, have a high 5-year survival rate (90%). Recent progress in understanding the pathogenesis of EOC and inflammatory signaling pathways revealed that type-2 cells frequently express a deleted or mutated TP53 (60-80%), or aberrations in BRCA1 (30-60%) and BRCA2 (15-30%). The deletion or mutation of TP53 results in a dysregulated inflammatory signal network and contributes to an immunosuppressive microenvironment. Thus, to be effective, EOC therapy may be necessary to cover two areas: (1) direct cytotoxic killing of cancer cells; (2) reversion of the immunosuppressive microenvironment. Presently the first strategy is advancing rapidly while the second strategy remains behind. Isolation and characterization of cancer stem cells (CSCs) have helped to confirm the dynamic role of the tumor microenvironment in promoting cancer metastasis and recurrence. Based on widely published in vitro and mouse-model data, some anti-inflammatory phytochemicals appear to exhibit activity in modulating the tumor microenvironment. Specifically, apiegenin, baicalein, curcumin, EGCG, genistein, luteolin, oridonin, quercetin, and wogonin repress NF-kappaB (NF-κB, a proinflammatory transcription factor) and inhibit proinflammatory cytokines such as TNF-α and IL-6. Additionally, most of these phytochemicals have been shown to stabilize p53 protein, sensitize TRAIL (TNF receptor apoptosis-inducing ligand) induced apoptosis, and prevent or delay chemotherapy-resistance. Recent studies further indicate that apigenin, genistein, kaempferol, luteolin, and quercetin potently inhibit VEGF production and suppress ovarian cancer cell metastasis in vitro. Lastly, oridonin and wogonin were suggested to suppress ovarian CSCs as is reflected by down-regulation of the surface marker EpCAM. Unlike NSAIDS (non-steroid anti-inflammatory drugs), well documented clinical data for phyto-active compounds are lacking. In order to evaluate objectively the potential benefit of these compounds in the treatment of ovarian cancer, strategically designed, large scale studies are warranted.

  • Michael A, Riley C, Bokaee S, Denyer M, Pandha H, Annels N. (2011) 'EN2: A candidate antigen for the development of targeted therapies in ovarian cancer.'. JOURNAL OF CLINICAL ONCOLOGY, 29 (15)
  • Morgan RM, Ismail M, Boxall A, Bhaat A, Hindley R, Michael A, Langley SM, Zylstra J, Pandha HS. (2011) 'ENGRAILED-2 (EN2): A HIGHLY SPECIFIC URINARY BIOMARKER FOR THE EARLY DIAGNOSIS OF PROSTATE CANCER'. EUR UROL SUPPL, 10 (2), pp. 64-64.
  • Morgan R, Boxall A, Bhatt A, Bailey M, Hindley R, Langley S, Whitaker HC, Neal DE, Ismail M, Whitaker H, Annels N, Michael A, Pandha H. (2011) 'Engrailed-2 (EN2): a tumor specific urinary biomarker for the early diagnosis of prostate cancer.'. Clin Cancer Res, United States: 17 (5), pp. 1090-1098.


    PURPOSE: Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men. EXPERIMENTAL DESIGN: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)] was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n = 82) and controls (n = 102). RESULTS: EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center. CONCLUSIONS: Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified.

  • Gray S, Pandha HS, Michael A, Middleton G, Morgan R. (2011) 'HOX genes in pancreatic development and cancer.'. JOP, Italy: 12 (3), pp. 216-219.


    The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to subsequent adult disease, and their potential both as diagnostic markers and therapeutic targets.

  • Kelly Z, Michael A, Butler-Manuel S, Pandha HS, Morgan RGL. (2011) 'HOX genes in ovarian cancer'. Journal of Ovarian Research, 4 (1)


    The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes), ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.

  • Lunt C, Barber N, Montgomery A, Kalsi V, Parker T, Michael A, Pandha H, Hindley R. (2010) 'CYTOREDUCTIVE NEPHRECTOMY IN THE TYROKINASE INHIBITOR ERA'. J ENDOUROL, 24, pp. A303-A303.
  • Michael A, Relph K, Pandha H. (2010) 'Emergence of potential biomarkers of response to anti-angiogenic anti-tumour agents.'. International Journal of Cancer, United States: 127 (6), pp. 1251-1258.


    Anti-angiogenic agents targeting tumour vasculature have an established place in clinical practice, and new data are constantly emerging. However, despite rapid clinical uptake, a very large number of questions regarding these agents remain unanswered. One of the main hurdles in clinical practice is lack of accurate and feasible ways of assessing response to drug beyond tumour reduction on conventional imaging. This review summarises recent developments in the field of biomarkers of response to anti-VEGF drugs.

  • Morgan RGL, Plowright L, Harrington K, Michael A, Pandha HS. (2010) 'Targeting HOX and PBX transcription factors in ovarian cancer'. BMC CANCER, 10 Article number ARTN 8
  • Michael A, John J, Meyer B, Pandha H. (2010) 'Activation and Genetic Modification of Human Monocyte-Derived Dendritic Cells using Attenuated Salmonella typhimurium'. THESCIENTIFICWORLDJOURNAL, 10, pp. 393-401.
  • Michael A, Syrigos K, Pandha H. (2009) 'Prostate cancer chemotherapy in the era of targeted therapy'. PROSTATE CANCER AND PROSTATIC DISEASES, 12 (1), pp. 13-16.
  • Michael A, Politi E, Havranek E, Corbishley C, Karapanagiotou L, Anderson C, Relph K, Syrigos KN, Pandha H. (2007) 'Prognostic significance of erythropoietin expression in human renal cell carcinoma.'. BJU Int, England: 100 (2), pp. 291-294.


    OBJECTIVES: To investigate, in a retrospective study, the expression of erythropoietin (Epo) in human renal cell carcinoma (RCC) and its correlation with overall survival, as Epo (an haematopoietic cytokine that regulates the production of red blood cells), with its receptor, was recently localized in non-haematopoietic tissues, e.g. liver, uterus, central nervous system, vascular endothelial cells and solid tumours. PATIENTS AND METHODS: We used data from 113 patients who had radical nephrectomy for RCC between 1990 and 2000, taking sections from formalin-fixed and paraffin wax-embedded tissue blocks. The association between Epo staining and the patients' characteristics was assessed by either chi-squared tests (for categorical variables) or two-sample independent t-tests (for continuous variables). RESULTS: Tissue from 37 patients (33%) was positive for cytoplasmic Epo expression; 76 (67%) samples were negative. Univariate hazard ratio analysis confirmed that those with positive Epo staining were more than twice as likely to die as those with negative staining (hazard ratio 2.34, 95% confidence interval 1.27-4.3). CONCLUSION: This study shows that the expression of Epo in RCC is adversely associated with overall survival. This is the first report of such an association, and might be explained by the loss of Von Hippel-Lindau protein function in clear cell RCC. The expression of Epo might have potential use in clinical trials when stratifying high-risk patients for adjuvant therapy after nephrectomy.

  • Michael A, Hedayati B, Dalgleish AG. (2007) 'Disease regression in malignant melanoma: Spontaneous resolution or a result of treatment with antioxidants, green tea, and pineapple cores? A case report'. INTEGR CANCER THER, 6 (1), pp. 77-79.
  • Michael A, Hill M, Maraveyas A, Dalgleish A, Lofts F. (2007) '13-cis-Retinoic Acid in Combination with Gemcitabine in the Treatment of Locally Advanced and Metastatic Pancreatic Cancer - Report of a Pilot Phase II Study'. Clinical Oncology, 19 (2), pp. 150-153.


    Aims: Adenocarcinoma of the pancreas is a cancer with extremely poor prognosis and limited therapeutic options. Retinoids are derivatives of vitamin A involved in the control of many biological functions, including cell growth and differentiation and the induction of apoptosis. On the basis of pre-clinical evidence and some clinical data, we conducted a phase II study of 13-cis-retinoic acid (13-cis-RA) in combination with gemcitabine in patients with unresectable pancreatic carcinoma. Materials and methods: Patients with histologically confirmed unresectable pancreatic carcinoma were treated with gemcitabine 1000 mg/m2 on days 8, 15, 22 plus 13-cis-RA 1 mg/kg on days 1e14 for six cycles. The end points included the objective response rate and median survival. Results: Thirty patients were recruited, 15 men and 15 women; 20 patients were evaluable. The median age was 65 years (range 44e79 years) and the median Karnofsky performance status was 80% (range 60e100%). The median followup was 21 months. One patient achieved a partial remission, seven patients had stable disease and 12 patients developed progressive disease. Toxicity was mainly haematological, with eight cases of grade 3 and four cases of grade 4 neutropenia, thrombocytopenia and anaemia. The median survival was 7.8 months (range 2.6e21.6 months). Conclusions: The combination of gemcitabine and 13-cis-RA was well tolerated, but we did not see improvement in the response rate. Further studies with other retinoids may be beneficial to patients with unresectable pancreatic cancer.

  • Hu JCC, Coffin RS, Davis CJ, Graham NJ, Groves N, Guest PJ, Harrington KJ, James ND, Love CA, McNeish I, Medley LC, Michael A, Nutting CM, Pandha HS, Shorrock CA, Simpson J, Steiner J, Steven NM, Wright D, Coombes RC. (2006) 'A phase I study of OncoVEX(GM-CSF), a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor'. CLINICAL CANCER RESEARCH, 12 (22), pp. 6737-6747.
  • Michael A, Ball G, Quatan N, Wushishi F, Russell N, Whelan J, Chakraborty P, Leader D, Whelan M, Pandha H. (2005) 'Delayed disease progression after allogeneic cell vaccination in hormone-resistant prostate cancer and correlation with immunologic variables'. Clin Cancer Res, 11 (12), pp. 4469-4478.


    PURPOSE: There are a significant number of patients with asymptomatic hormone-resistant prostate cancer who have increasing prostate-specific antigen (PSA) levels but little or no evaluable disease. The immunogenicity and minimal toxicity associated with cell-based vaccine therapy makes this approach attractive for these patients. EXPERIMENTAL DESIGN: We have evaluated a vaccine comprising monthly intradermal injection of three irradiated allogeneic prostate cell lines (8 x 10(6) cells each) over 1 year. The first two doses were supplemented with bacille Calmette-Guerin as vaccine adjuvant. Twenty-eight hormone-resistant prostate cancer patients were enrolled. Patients were assessed clinically and PSA levels were measured monthly. Radiologic scans (X-ray, computed tomography, and bone scan) were taken at baseline and at intervals throughout the treatment period. Comprehensive monthly immunologic monitoring was undertaken including proliferation studies, activation markers, cytokine protein expression, and gene copy number. This longitudinal data was analyzed through predictive modeling using artificial neural network feed-forward/back-propagation algorithms with multilayer perceptron architecture. RESULTS: Eleven of the 26 patients showed statistically significant, prolonged decreases in their PSA velocity (PSAV). None experienced any significant toxicity. Median time to disease progression was 58 weeks, compared with recent studies of other agents and historical control values of around 28 weeks. PSAV-responding patients showed a titratable T(H)1 cytokine release profile in response to restimulation with a vaccine lysate, while nonresponders showed a mixed T(H)1 and T(H)2 response. Furthermore, immunologic profile correlated with PSAV response by artificial neural network analysis. We found predictive power not only in expression of cytokines after maximal stimulation with phorbol 12-myristate 13-acetate, but also the method of analysis (qPCR measurement of IFN-gamma > qPCR measurement tumor necrosis factor-alpha > protein expression of IFN-gamma > protein expression of interleukin 2). CONCLUSIONS: Whole cell allogeneic vaccination in hormone-resistant prostate cancer is nontoxic and improves the natural history of the disease. Longitudinal changes in immunologic function in vaccinated patients may be better interpreted through predictive modeling using tools such as the artificial neural network rather than periodic "snapshot" readouts.

  • Michael A, Maravcyas A, Hill M, Wasan H, Lofts F. (2001) 'Preliminary results of phase I/II study to investigate the use of gemcitabine in combination with ralitrexed in locally advanced or metastatic adenocarcinoma of the pancreas'. BRITISH JOURNAL OF CANCER, 85, pp. 55-55.

Conference papers

  • Michael A, McGrath S, Annels N, Denyer M, Morgan R, Pandha H. (2015) 'Engrailed 2 protein (EN2) as a novel biomarker in epithelial ovarian cancer'. ELSEVIER SCI LTD EUROPEAN JOURNAL OF CANCER, Vienna, AUSTRIA: European Cancer Congress 51, pp. S91-S91.
  • McNeish IA, Michael A, Twelves C, Glasspool R, Ajaz MA, Morrison R, Xeniou O, Brown R, Fisher K, Blanc C. (2015) 'A phase I/II study of Enadenotucirev, an oncolytic Ad11/Ad3 chimeric group B adenovirus, administered intraperitoneally (IP): Dose finding and proof of concept in platinum-resistant epithelial ovarian cancer.'. AMER SOC CLINICAL ONCOLOGY JOURNAL OF CLINICAL ONCOLOGY, Chicago, IL: Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) 33 (15)
  • Fisher RA, Rowan A, Stares M, Webster-Smith MF, Lewis R, Kilbum LS, Nicol D, Stewart G, Michael A, Vasudev N, Hazen S, Turalijic S, Pickering LM, Gore ME, Snowdon C, Bliss JM, Swanton C, Larkin JMG. (2014) 'A-PREDICT: A phase II study of axitinib in patients with metastatic renal cell cancer unsuitable for nephrectomy (CRUKE/11/061)'. AMER SOC CLINICAL ONCOLOGY JOURNAL OF CLINICAL ONCOLOGY, Chicago, IL: 50th Annual Meeting of the American-Society-of-Clinical-Oncology 32 (15)
  • Kelly Z, Pandha H, Madhuri K, Morgan R, Michael A. (2012) 'HOX GENE EXPRESSION IN OVARIAN CANCER'. OXFORD UNIV PRESS ANNALS OF ONCOLOGY, Vienna, AUSTRIA: 37th Congress of the European-Society-for-Medical-Oncology (ESMO) 23, pp. 68-68.
  • Kelly Z, Pandha H, Morgan R, Michael A. (2012) 'HXR9 AND PARP INHIBITION -A NOVEL THERAPEUTIC IN OVARIAN CANCER'. OXFORD UNIV PRESS ANNALS OF ONCOLOGY, Vienna, AUSTRIA: 37th Congress of the European-Society-for-Medical-Oncology (ESMO) 23, pp. 325-325.
  • McGrath S, Annels NE, Madhuri TK, Haagsma B, Larbi ED, Pandha HS, Michael A. (2012) 'Engrailed protein: A cancer-specific marker in epithelial ovarian cancer'. AMER SOC CLINICAL ONCOLOGY JOURNAL OF CLINICAL ONCOLOGY, Chicago, IL: 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) 30 (15)
  • Michael A, Riley, C, Bokaee S, Denyer M, Pandha H, Annels N. (2011) 'EN2: A candidate antigen for the development of targeted therapies in ovarian cancer.'. JCO, Chicago: ASCO (J Clin)


    Background: Ovarian cancer remains the most lethal gynaecologic tumour in the Western world. Stimulation of the immune system to consolidate response to chemotherapy can potentially be beneficial however so far none of the vaccination strategies have offered survival advantage. Thus identifying and targeting clinically relevant antigens for immunotherapy continues to be an important research strategy. We have evaluated Engrailed-2 (EN2) as a potential target for vaccine strategy. EN2 is a homeodomain-containing transcription factor with a multifunctional role in neural development. There is evidence that over-expression of EN2 protein maybe linked to tumour development. Methods: Ovarian cancer cell lines were analysed by FACS for EN2 cell surface expression. EN2 expression in ovarian cancer tissue arrays were done by immunohistochemistry. A serum analysis (ELISA) was done to evaluate the presence of antibodies to EN2 in ovarian cancer patients and age-matched controls. A set of potentially immunogenic HLA-A2 restricted epitopes from the EN2 protein was identified using a computer algorithm SYFPEITHI. These peptides have been tested on HLA-A2 positive ovarian cancer patients’ PBMC using an in vitro culture method. The specificity of these T cell lines was analysed against T2 target cells loaded with or without EN2 peptides Results: Cell surface expression of EN2 was observed in ovarian cancer cell lines OVCAR3, OV90, CaOV-3, ES-2 and SKOV-3 of which ES-2 and SKOV3 showed strong expression. EN2 was also present in approximately 80% of ovarian cancer tissues whereas EN-2 expression was very low (<10%) or absent in normal tissues. Out of the 67 ovarian cancer patients 20.9% (14/67) had antibodies against EN2 compared to 2.4% (1/42) of age-matched female controls. 4 of the identified EN2 epitopes were able to generate peptide specific cytotoxic T lymphocytes in the ovarian cancer patients tested. Conclusions: The over-expression and immunogenicity of EN2 in ovarian cancer makes it a credible antigen to exploit as a novel target for ovarian cancer immunotherapy. ž

  • Coward JIG, Larbi ED, Pandha H, Michael A. (2011) 'The effect of age on first-line sunitinib treatment in patients with renal cell carcinoma (RCC).'. J Clin Oncol 29: 2011 (suppl; abstr e15096), Chicago USA: ASCO


    Background: Sunitinib is a first line treatment for majority of patients with metastatic RCC. The recommended dose of 50mg often results in a spectrum of serious side effects which subsequently lead to dose reduction and may have an impact on response rates. Methods: We conducted a retrospective analysis of 62 RCC patients from single institution treated with sunitinib between September 2007-May 2010. Patients were stratified according to age groups, into ≤ 70 year old (y.o.) and > 70 y.o. to compare tolerability, response rates and median survival. Results: All patients were evaluable for toxicity, 55 patients were evaluable for response. 38 (61.2%) were ≤ 70 y.o. and 24 (38.8%) were >70y.o. 2 patients (5%) of ≤70 and 5 (20%) of > 70y.o. were non-evaluable for response due to early treatment discontinuation. The response rate was 36% in ≤70y.o. and 21% in >70 y.o., stable disease (SD) was observed in 41% ≤70 y.o. vs 47% in the older age group and progressive disease PD:22% vs 31.5% respectively. 24 (38.7%) of patients required dose reductions after the first or second cycle- 12 (33%) in ≤70 vs 11 (59%) in >70 yrs old. A small number of patients presented with PS 2 and these were started on a reduced dose of 37.5mg: 3 (8%) in ≤70y.o. and 11 (58%) > 70y.o. Toxcities were comparable in both groups however grade 3 palmar-plantar erythema (PPE) and mucositis (18% vs 1.6% and 18 vs 8% respectively) were more prevalent in the younger cohort. Grade 3 diarrhoea and fatigue were more common in older patients (10% in >70y.o vs 1.6% in ≤70y.o. and 16% vs 9.6% respectively). Median survival was 23 months for both age groups. Conclusions: Elderly patients more commonly require dose reduction due to poor performance status and toxicity profile. The objective response rate is lower with the lower dose intensity however the rate of disease stabilisation is comparable in both groups. The lower dose of Sunitinib is well tolerated in the elderly and this regimen should be considered for older patients with poor performance status.

  • Gungor H, Saleem A, Agarwal R, Blagden S, Michael A, Stronach EA, Chen M, Pickford E, Rama NR, Lewis YL, Carme SC, Salinas C, Smith DA, Krachey E, Santiago-Walker A, Gunn RN, El-Bahrawy M, Babar, SA, Morris R, Gabra H. (2011) 'Pharmacokinetic (PK)/pharmacodynamic (PD) analysis of escalating repeat doses of the AKT inhibitor GSK2141795 (GSK795) in patients (pts) with ovarian cancer.'. J Clin Oncol 29: 2011 (suppl; abstr 5064), Chicago USA: ASCO


    Background: GSK795 is a potent, ATP-competitive, pan AKT inhibitor. The purpose of this study was to characterize the relationship between AKT inhibition by GSK795 and downstream effects in platinum resistant ovarian cancer pts. Methods: Pts with recurrent platinum-resistant ovarian cancer received 25, 50 or 75mg of oral GSK795 daily. Dynamic FDG-PET scans and paired tumor biopsies (PTB) were performed prior to first dose and at 2 and/or 4 weeks post treatment. Semi-quantitative (SUV) and quantitative (Ki, MRglu) PET PD parameters were derived. PTB were analyzed by immunohistochemistry (IHC) for PD marker expression. PK samples were obtained in parallel. Response was monitored by RECIST and CA125 criteria. Results: 12 pts have been treated on study: 4 at 25mg, 4 at 50mg and 4 at 75mg. After completion of the 2 or 4 week post-treatment PD assessment, all eligible pts underwent intra-subject dose escalation to 75mg. The most common drug-related adverse events (≥ 10%) were decreased appetite (18%) and vomiting (18%), all G1/2. Mean Cmax and AUC24 increased with increasing doses and increased 1.2-fold from Week 2 to Week 4 where 2 and 4 week doses were the same. Median Tmax was 4 h. Overall tumor FDG metabolism decreased in 71% of tumors with treatment, although inter- and intra-patient variability in tumor uptake measurements following therapy was seen. There was no clear temporal or dose-response effect in FDG uptake. IHC analysis of PTB from 5 pts dosed at either 50 or75mg indicated that pAKT levels increased in 2/2 pts dosed at 75mg, pPRAS40 levels decreased in 4/5 pts, and Ki67 levels decreased in 4/5 pts after treatment with GSK795. 8/12 pts had stable disease and 4/12 had progressive disease by RECIST criteria at week 4. Currently 4 pts are still on the study, 2 > 24 weeks, with tumor regressions of 26% and 11% and CA125 decreases of 70% and 58% respectively. Conclusions: A dose response relationship between changes in FDG-PET and GSK795 was not observed in pts dosed from 25 to 75mg daily. Evidence of AKT pathway inhibition was observed in PTB from pts dosed with 50 or 75mg GSK795. Clinical activity evidenced by tumor regressions and CA125 decreases was also observed.

  • Michael A, Zylstra J, Pandha H. (2011) 'The sun study-a biobank of sequential blood samples from patients with prostate cancer'. WILEY-BLACKWELL BRITISH JOURNAL OF SURGERY, Royal Coll Surgery, Dublin, IRELAND: Annual Meeting of the Society-of-Academic-and-Research-Surgery 98, pp. 50-50.
  • Larbi E, Madhuri TK, Essapen S, Michael A. (2010) 'The impact of age on first-line chemotherapy treatment of epithelial ovarian cancer and primary peritoneal carcinoma'. Chicago USA: ASCO (J Clin Oncol 28:15s, 2010 (suppl; abstr 5118))


    Background: Standard treatment for epithelial ovarian (EOC) and primary peritoneal (PP) cancer is combination of surgery and chemotherapy. Most commonly used first-line drugs are carboplatin and paclitaxel (C/P). Treatment decisions involving elderly patients are complex and single agent carboplatin (C) is often preferred. To help the decision process we analysed the toxicity profile and outcome for elderly patients treated first line with both: C/P and C alone. Methods: A retrospective analysis of 82 elderly patients (> 75 years) treated for EOC and PP cancer between April 1996 and October 2009 was performed. Age, comorbidities, CA-125 at diagnosis, histology, stage, outcome of cytoreductive surgery (CRS), chemotherapy regimen, toxicity and clinical response were recorded. Results: The majority, 76% (63/82) of patients had serous ovarian cancer with 58.5% presenting as FIGO stage 3c, median CA-125 of 340.2 U/mL (range: 5-5702). 67.1% (55/82) had CRS with 61.9% (34) optimally debulked. 84.2% of patients (69/82) received chemotherapy and were therefore evaluable for the purpose of this analysis. 94.2% (65/69) completed treatment (mean number of cycles = 5.1). 35.4% (23/65) received C/P and 63.1% (41/65) received single agent C. The commonest complication was peripheral neuropathy- 56.5% (13/23) in combination arm. Treatment was deferred mainly due to haematological toxicity: neutropaenia - 13.9% (6/43) in the C arm and 11.1% (3/27) in C/P; grade 3/4 thrombocytopaenia-4 (3-C, 1-P/C); grade 3-anaemia-1 (C). Dose reduction was required for 46.1% (12/26) in the combination arm and 25.5% (11/43) in the C arm. There were 35 dose delays-34.6% (9/26) C/P and 60.4% (26/43) C. Median survival for this group of patients was 21.3months. Median PFS was 8.8 months in C/P arm and 7 months in the C arm (95% CI-0.71 to1.8-not statistically significant). Conclusions: The toxicity of combination treatment with C/P is comparable to single agent C in elderly population with frequent dose delays and dose reductions. Initial assessment of comorbidities and performance status is essential however effort should be made to offer patients optimal treatment with the combination regimen.

  • Michael A, Plowright L, Boxall A, Bhatt A, Di Palma S, Parker C, Pandha H. (2010) 'Evaluation of EN2 as a urine-based biomarker for prostate cancer.'. J Clin Oncol 28, 2010 (suppl; abstr e15129), Chicago USA: ASCO


    Background: Prostate cancer is a leading cause of cancer related death in men but its diagnosis is still complicated by the lack of a highly predictive biochemical marker. Here we show that the transcription factor Engrailed-2 is secreted from prostate tumours in a highly specific manner and is present in the urine of men with prostate cancer. Methods: Urine was collected under standardised conditions from men with prostate cancer, or with non-cancerous conditions of the prostate such as benign prostatic hypertrophy, or men who were found to have no prostate abnormalities after saturation biopsy. Results: Engrailed-2 protein was detected in the untreated, unconcentrated urine of 62% of men with prostate cancer, but only 3% of men with no prostatic abnormalities (n=258, p<0.001). Conclusions: Thus Engrailed-2 is a potential diagnostic marker for prostate cancer.

Book chapters

  • Michael A, Pandha H. (2013) 'Presentation and Symptomatology of Prostate Cancer'. in Tewari AK (ed.) Prostate Cancer: A Comprehensive Perspective Springer Science & Business Media Article number 38 , pp. 467-471.


    27. Introduction. In 2010, 217,730 men will have been diagnosed with prostate cancer (PCa) in the United States of America (USA), and around 32,730 will have died from the disease [1]. Depending on the extent of prostate-specific antigen ...

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