Prof Hing Leung - Prostate Cancer Biology
Introduction
Prostate cancer is a major global health issue, and its management remains controversial. A refined understanding of how aberrant signalling drives prostate carcinogenesis will help develop better prognostic biomarkers and therapeutic targets. FGF receptor and ERK5 in particular have been implicated in prostate cancer.
Work in our lab continues to explore the significance of these signalling pathways, to investigate tumour biology using in vitro and in vivo models and to develop specific small molecule inhibitors. Working closely with colleagues in the NHS, Glasgow University and the CRUK Scotland Institute, we are developing infrastructure required for the necessary biorespository and other ongoing translational research programmes.
Potential Postdocs, Clinical Fellows and Students
We are always keen to hear from good people. Please email me (h.leung@beatson.gla.ac.uk) with a copy of your CV including the details of two referees.
Email
Lab Report
Key Publications
Patel R, Gao M, Ahmad I, Fleming J, Singh LB, Rai TS, McKie AB, Seywright M, Barnetson RJ, Edwards J, Sansom OJ and Leung HY. Sprouty2, PTEN and PP2A interact to regulate prostate cancer progression. Journal of Clinical Investigation. 2013; 123: 1157-75
Gao M, Patel R, Ahmad I, Fleming J, Edwards J, McCracken S, Sahadevan K, Seywright M, Norman J, Sansom O, Leung HY. SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis. EMBO Mol Med. 2012; 4: 776-90
Ahmad I, Patel R, Singh LB, Nixon C, Seywright M, Barnetson RJ, Brunton V, Muller WJ, Edwards J, Sansom OJ, Leung HY. HER2 overcomes PTEN (loss) induced Senescence to cause Aggressive Prostate Cancer. Proc Nat Acad Sci. 2011; 108: 6392-7
Ahmad I, Morton J, Singh BL, Radulescu SM, Ridgway RA, Patel S, Woodgett J, D, Winton DL, Taketo MM, Wu XR Leung HY, Sansom OJ. β-catenin activation synergises with PTEN loss to cause bladder cancer formation. Oncogene. 2011; 30: 178-89
Wiltshire C, Singh BL, Stockley J, Fleming J, Doyle B, Barnetson R, Robson CN, Kozielski F and Leung HY. Docetaxel resistant prostate cancer cells remain sensitive to S-trityl L-cysteine (STLC) mediated Eg5 inhibition. Mol Cancer Therapeutics. 2010; 9: 1730-9
McCracken SR, Ramsay A, Heer R, Mathers ME, Jenkins BL, Edwards J, Robson CN, Marquez R, Cohen P, Leung HY. Aberrant expression of extracellular signal-regulated kinase 5 in human prostate cancer. Oncogene. 2008; 27: 2978-88
Biography
Education and qualifications
1986: MB ChB, University of Aberdeen
1990: FRCS (Glas) , Royal College of Physicians and Surgeons of Glasgow
1994: PhD, University of London, Supervisor Nick Lemoine
1997: FRCS (Urol), Royal Colleges of Surgeons (UK & Ireland)
Appointments
2006-present: Professor of Urology and Surgical Oncology, University of Glasgow; Group Leader, CRUK Scotland Institute; Consultant Urological Surgeon, NHS Greater Glasgow and Clyde
2002-2006: Professor of Urological Oncology, University of Newcastle upon Tyne
1999-2002: Senior Lecturer, University of Newcastle upon Tyne
1995-1998: Clinical Lecturer, University of Newcastle upon Tyne
1990-1994: Clinical Research Fellow, Imperial Cancer Research Fund
1987-1989: Surgical Registrar, Birmingham Rotation
Current committee membership
Movember GAP Committee
Prostate Cancer UK Trustee
Chairman, Section of Academic Urology, British Association of Urological Surgeons
MRC College of Experts & Molecular and Cellular Medicine Board
Honours and awards
The Karl Storz Harold Hopkins Golden Telescope Award, British Association of Urological Surgeons, 2008
Founding member of the Northern Institute for Cancer Research, University of Newcastle upon Tyne
Recent Publications
2023
AlRasheedi M, Han S, Thygesen H, Neilson M, Hendry F, Alkarn A, Maclay JD, Leung HY. A Comparative Evaluation of Mediastinal Nodal SUVmax and Derived Ratios from (18)F-FDG PET/CT Imaging to Predict Nodal Metastases in Non-Small Cell Lung Cancer. Diagnostics (Basel). 2023;13.
Bennett SS, Leung HY, Ahmad I. A cohort analysis of patients receiving neoadjuvant androgen deprivation therapy prior to robot-assisted laparoscopic prostatectomy during the Covid-19 pandemic. J Clin Urol. 2023;16:131-139.
Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.
Rushworth LK, Loveridge C, Salji M, MacLeod M, Mui E, Sumpton D, Neilson M, Hedley A, Alexander L, McCartney E, Patel R, Wallace J, Delles C, Jones R, Leung HY. Phase II proof-of-concept study of atorvastatin in castration-resistant prostate cancer. BJU Int. 2023;131:236-243.
Sandilands E, Freckmann EC, Cumming EM, Román-Fernández A, McGarry L, Anand J, Galbraith L, Mason S, Patel R, Nixon C, Cartwright J, Leung HY, Blyth K, Bryant DM. The small GTPase ARF3 controls invasion modality and metastasis by regulating N-cadherin levels. Journal of Cell Biology. 2023;222.
Taggart R, Dutto L, Leung HY, Salji M, Ahmad I. A contemporary analysis of disease upstaging of Gleason 3 + 3 prostate cancer patients after robot-assisted laparoscopic prostatectomy. Cancer Med. 2023.
Tibbo AJ, Hartley A, Vasan R, Shaw R, Galbraith L, Mui E, Leung HY, Ahmad I. MBTPS2 acts as a regulator of lipogenesis and cholesterol synthesis through SREBP signalling in prostate cancer. British Journal of Cancer. 2023;128: 1991–1999
2022
Adam C, Bray TL, Pérez-López AM, Tan EH, Rubio-Ruiz B, Baillache DJ, Houston DR, Salji MJ, Leung HY, Unciti-Broceta A. A 5-FU Precursor Designed to Evade Anabolic and Catabolic Drug Pathways and Activated by Pd Chemistry In Vitro and In Vivo. J Med Chem. 2022; 65:552–561
Blomme A, Peter C, Mui E, Rodriguez Blanco G, An N, Mason LM, Jamieson LE, McGregor GH, Lilla S, Ntala C, Patel R, Thiry M, Kung SHY, Leclercq M, Ford CA, Rushworth LK, McGarry DJ, Mason S, Repiscak P, Nixon C, Salji MJ, Markert E, MacKay GM, Kamphorst JJ, Graham D, Faulds K, Fazli L, Gleave ME, Avezov E, Edwards J, Yin H, Sumpton D, Blyth K, Close P, Murphy DJ, Zanivan S, Leung HY. THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer. EMBO Molecular Medicine. 2022;4:e14764
Freckmann EC, Sandilands E, Cumming E, Neilson M, Román-Fernández A, Nikolatou K, Nacke M, Lannagan TRM, Hedley A, Strachan D, Salji M, Morton JP, McGarry L, Leung HY, Sansom OJ, Miller CJ, Bryant DM. Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging. Nat Commun. 2022;13:5317.
Gómez V, Galazi M, Weitsman G, Monypenny J, Al-Salemee F, Barber PR, Ng K, Beatson R, Szokol B, Orfi L, Mullen G, Vanhaesebroeck B, Chowdhury S, Leung HY, Ng T. HER2 Mediates PSMA/mGluR1-Driven Resistance to the DS-7423 Dual PI3K/mTOR Inhibitor in PTEN Wild-type Prostate Cancer Models. Mol Cancer Ther. 2022;21:667-676.
Patel R, Ford CA, Rodgers L, Rushworth LK, Fleming J, Mui E, Zhang T, Watson D, Lynch V, Mackay G, Sumpton D, Sansom OJ, Vande Voorde J, Leung HY. Cyclocreatine suppresses creatine metabolism and impairs prostate cancer progression. Cancer Res. 2022;82: 2565–2575.
Salji MJ, Blomme A, Däbritz JHM, Repiscak P, Lilla S, Patel R, Sumpton D, van den Broek NJF, Daly R, Zanivan S, Leung HY. Multi-omics & pathway analysis identify potential roles for tumor N-acetyl aspartate accumulation in murine models of castration-resistant prostate cancer. iScience. 2022;25:104056.
Sooriakumaran P, Wilson C, Rombach I, Hassanali N, Aning J, A DL, Cathcart P, Eden C, Ahmad I, Rajan P, Sridhar A, Bryant RJ, Elhage O, Cook J, Leung H, Soomro N, Kelly J, Nathan S, Donovan JL, Hamdy FC. Feasibility and safety of radical prostatectomy for oligo-metastatic prostate cancer: the Testing Radical prostatectomy in men with prostate cancer and oligo-Metastases to the bone (TRoMbone) trial. BJU Int. 2022;130:43-53.
Gaba F, Tipping WJ, Salji M, Faulds K, Graham D, Leung HY. Gaba F, Tipping WJ, Salji M, Faulds K, Graham D, Leung HY. Raman Spectroscopy in Prostate Cancer: Techniques, Applications and Advancements. Cancers (Basel). 2022;14. Cancers (Basel). 2022;14:1535
2021
Cangiano M, Grudniewska M, Salji MJ, Nykter M, Jenster G, Urbanucci A, Granchi Z, Janssen B, Hamilton G, Leung HY, Beumer IJ. Gene Regulation Network Analysis on Human Prostate Orthografts Highlights a Potential Role for the JMJD6 Regulon in Clinical Prostate Cancer. Cancers (Basel). 2021;13.
Clement KD, Day L, Rooney H, Neilson M, Birrell F, Salji M, Norman E, Clark R, Patel A, Morrison J, Leung HY. Developing a coordinate-based strategy to support cognitive targeted prostate biopsies and correlative spatial-histopathological outcome analysis. Asian J Androl. 2021;23(3):231-235.
Galbraith LCA, Mui E, Nixon C, Hedley A, Strachan D, MacKay G, Sumpton D, Sansom OJ, Leung HY, Ahmad I. PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer. Oncogene. 2021;40:2355-2366.
Laskar P, Somani S, Mullin M, Tate RJ, Warzecha M, Bowering D, Keating P, Irving C, Leung HY, Dufès C. Octadecyl chain-bearing PEGylated poly(propyleneimine)-based dendrimersomes: physicochemical studies, redox-responsiveness, DNA condensation, cytotoxicity and gene delivery to cancer cells. Biomater Sci. 2021;9: 1431-1448
Martinez RS, Salji MJ, Rushworth L, Ntala C, Rodriguez Blanco G, Hedley A, Clark W, Peixoto P, Hervouet E, Renaude E, Kung SHY, Galbraith LCA, Nixon C, Lilla S, Mackay GM, Fazli L, Gaughan L, Sumpton D, Gleave ME, Zanivan S, Blomme A, Leung HY. SLFN5 regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer. Cancer Res. 2021; 82: 3664-78
McAteer MA, O'Connor JPB, Koh DM, Leung HY, Doran SJ, Jauregui-Osoro M, Muirhead N, Brew-Graves C, Plummer ER, Sala E, Ng T, Aboagye EO, Higgins GS, Punwani S. Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers. Br J Cancer. 2021:1-4.
Nacke M, Sandilands E, Nikolatou K, Román-Fernández Á, Mason S, Patel R, Lilla S, Yelland T, Galbraith LCA, Freckmann EC, McGarry L, Morton JP, Shanks E, Leung HY, Markert E, Ismail S, Zanivan S, Blyth K, Bryant DM. An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism. Nat Commun. 2021;12:1623.
Ntala C, Salji M, Salmond J, Officer L, Teodosio AV, Blomme A, McGhee EJ, Powley I, Ahmad I, Kruithof-de Julio M, Thalmann G, Roberts E, Goodyear CS, Jamaspishvili T, Berman DM, Carlin LM, Le Quesne J, Leung HY. Analysis of Prostate Cancer Tumor Microenvironment Identifies Reduced Stromal CD4 Effector T-cell Infiltration in Tumors with Pelvic Nodal Metastasis. Eur Urol Open Sci. 2021;29:19-29.
Campbell KJ, Leung HY. Evasion of cell death: A contributory factor in prostate cancer development and treatment resistance. Cancer Lett. 2021;520:213-221.
Hartley A, Leung HY, Ahmad I. Targeting the BAF complex in advanced prostate cancer. Expert Opin Drug Discov. 2021; 16:173-181.
2020
Bellier J, Nokin MJ, Caprasse M, Tiamiou A, Blomme A, Scheijen JL, Koopmansch B, MacKay GM, Chiavarina B, Costanza B, Rademaker G, Durieux F, Agirman F, Maloujahmoum N, Cusumano PG, Lovinfosse P, Leung HY, Lambert F, Bours V, Schalkwijk CG, Hustinx R, Peulen O, Castronovo V, Bellahcene A. Methylglyoxal Scavengers Resensitize KRAS-Mutated Colorectal Tumors to Cetuximab. Cell reports. 2020;30(5):1400-1416 e1406.
Blomme A, Ford CA, Mui E, Patel R, Ntala C, Jamieson LE, Planque M, McGregor GH, Peixoto P, Hervouet E, Nixon C, Salji M, Gaughan L, Markert E, Repiscak P, Sumpton D, Rodriguez Blanco G, Lilla S, Kamphorst JJ, Graham D, Faulds K, MacKay GM, Fendt S-M, Zanivan S, Leung HY. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nat Commun. 2020; 11: 2508
Clement KD, Day L, Rooney H, Neilson M, Birrell F, Salji M, Norman E, Clark R, Patel A, Morrison J, Leung HY. Developing a coordinate-based strategy to support cognitive targeted prostate biopsies and correlative spatial-histopathological outcome analysis. Asian J Androl. 2020;23:231-235
Hartley A, Leung HY, Ahmad I. Targeting the BAF complex in advanced prostate cancer. Expert Opinion on Drug Discovery. 2020:1-9.
Loveridge CJ, Slater S, Campbell KJ, Nam NA, Knight J, Ahmad I, Hedley A, Lilla S, Repiscak P, Patel R, Salji M, Fleming J, Mitchell L, Nixon C, Strathdee D, Neilson M, Ntala C, Bryson S, Zanivan S, Edwards J, Robson CN, Goodyear CS, Blyth K, Leung HY. BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration. Oncogene. 2020; 39: 1797–1806
Malviya G, Patel R, Salji M, Martinez RS, Repiscak P, Mui E, Champion S, Mrowinska A, Johnson E, AlRasheedi M, Pimlott S, Lewis D, Leung HY. 18F-Fluciclovine PET metabolic imaging reveals prostate cancer tumour heterogeneity associated with disease resistance to androgen deprivation therapy. EJNMMI Research. 2020;10(1):143.
McAllister M, Constâncio V, Patek S, Gan H, Bailey P, Wheadon H, Underwood M, Leung H, Edwards J. Inflammatory infiltration is associated with AR expression and poor prognosis in hormone naïve prostate cancer. Prostate. 2020; 80: 1353-1364
McAllister MJ, McCall P, Dickson A, Underwood MA, Andersen D, Holmes E, Markert E, Leung HY, Edwards J. Androgen receptor phosphorylation at serine 81 and serine 213 in castrate-resistant prostate cancer. Prostate cancer and prostatic diseases.2020; 23:596–606
Mevel R, Steiner I, Mason S, Galbraith LCA, Patel R, Fadlullah MZH, Ahmad I, Leung HY, Oliveira P, Blyth K, Baena E, Lacaud G. RUNX1 marks a luminal castration resistant lineage established at the onset of prostate development. eLife. 2020;9:e60225.
Patel R, Brzezinska EA, Repiscak P, Ahmad I, Mui E, Gao M, Blomme A, Harle V, Tan EH, Malviya G, Mrowinska A, Loveridge CJ, Rushworth LK, Edwards J, Ntala C, Nixon C, Hedley A, Mackay G, Tardito S, Sansom OJ, Leung HY. Activation of beta-Catenin Cooperates with Loss of Pten to Drive AR-Independent Castration-Resistant Prostate Cancer. Cancer research. 2020;80(3):576-590.
Pritchard JJG, Hamilton G, Hurst CD, Fraser S, Orange C, Knowles MA, Jones RJ, Leung HY, Iwata T. Monitoring of urothelial cancer disease status after treatment by digital droplet PCR liquid biopsy assays. Urol Oncol. 2020;38: 737.e1-737.e10
Rushworth LK, Harle V, Repiscak P, Clark W, Shaw R, Hall H, Bushell M, Leung HY, Patel R. In vivo CRISPR/Cas9 knockout screen: TCEAL1 silencing enhances docetaxel efficacy in prostate cancer. Life Sci Alliance. 2020;3(12).
Rushworth LK, Hewit K, Munnings-Tomes S, Somani S, James D, Shanks E, Dufes C, Straube A, Patel R, Leung HY. Repurposing screen identifies mebendazole as a clinical candidate to synergise with docetaxel for prostate cancer treatment. British journal of cancer. 2020; 122: 517–527
Scarsbrook AF, Bottomley D, Teoh EJ, Bradley KM, Payne H, Afaq A, Bomanji J, van As N, Chua S, Hoskin P, Chambers A, Cook GJ, Warbey VS, Han S, Leung HY, Chau A, Miller MP, Gleeson FV, group Fs. Impact of (18)F-fluciclovine positron emission tomography on the management of patients with recurrence of prostate cancer: results from the FALCON trial. Int J Radiat Oncol Biol Phys. 2020; 107: 316-324
2019
Birrell F, Leung HY. The Scottish prostate cryotherapy service-the role of the clinical nurse specialist. British journal of nursing (Mark Allen Publishing). 2019; 28: S12-s16.
Kdadra M, Hockner S, Leung H, Kremer W, Schiffer E. Metabolomics Biomarkers of Prostate Cancer: A Systematic Review. Diagnostics (Basel). 2019; 9: E21
Laskar P, Somani S, Campbell SJ, Mullin M, Keating P, Tate RJ, Irving C, Leung HY, Dufes C. Camptothecin-based dendrimersomes for gene delivery and redox-responsive drug delivery to cancer cells. Nanoscale. 2019; 11: 20058-20071
McAllister MJ, Underwood MA, Leung HY, Edwards J. A review on the interactions between the tumor microenvironment and androgen receptor signaling in prostate cancer. Transl Res 2019; 206: 91-106
2018
Altwaijry N, Somani S, Parkinson JA, Tate RJ, Keating P, Warzecha M, Mackenzie GR, Leung HY, Dufes C. Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-alpha, TRAIL, and interleukin-12. Drug Deliv 2018; 25: 679-89
Galbraith L, Leung HY, Ahmad I. Lipid pathway deregulation in advanced prostate cancer. Pharmacol Res 2018; 131: 177-84.
Hewit K, Sandilands E, Martinez RS, James D, Leung HY, Bryant DM, Shanks E, Markert EK. A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor. Cell Death Dis 2018; 9: 1069
Patel R, Fleming J, Mui E, Loveridge C, Repiscak P, Blomme A, Harle V, Salji M, Ahmad I, Teo K, Hamdy FC, Hedley A, van den Broek N, Mackay G, Edwards J, et al. Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1. EMBO Mol Med 2018; 10.
Salji M, Hendry J, Patel A, Ahmad I, Nixon C, Leung HY. Peri-prostatic Fat Volume Measurement as a Predictive Tool for Castration Resistance in Advanced Prostate Cancer. Eur Urol Focus 2018; 4: 858-866
2017
Loveridge CJ, Mui EJ, Patel R, Tan EH, Ahmad I, Welsh M, Galbraith J, Hedley A, Nixon C, Blyth K, Sansom O, Leung HY. Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse Model of Prostate Carcinogenesis. Cancer Res 2017; 77: 3158-68
Loveridge CJ, van 't Hof RJ, Charlesworth G, King A, Tan EH, Rose L, Daroszewska A, Prior A, Ahmad I, Welsh M, Mui EJ, Ford C, Salji M, Sansom O, Blyth K, Leung HY. Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity. Sci Rep 2017; 7: 13241
Munkley J, McClurg UL, Livermore KE, Ehrmann I, Knight B, McCullagh P, McGrath J, Crundwell M, Harries LW, Leung HY, Mills IG, Robson CN, Rajan P, Elliott DJ. The cancer-associated cell migration protein TSPAN1 is under control of androgens and its upregulation increases prostate cancer cell migration. Sci Rep 2017; 7: 5249
Patek S, Willder J, Heng J, Taylor B, Horgan P, Leung H, Underwood M, Edwards J. Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients. Oncotarget 2017; 8: 4875-87
2016
Ahmad I, Mui E, Galbraith L, Patel R, Tan EH, Salji M, Rust AG, Repiscak P, Hedley A, Markert E, Loveridge C, van der Weyden L, Edwards J, Sansom OJ, Adams DJ, Leung HY. Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer. Proc Natl Acad Sci USA. 2016; 113: 8290-5
Kerr L, Rewhorn MJ, Longmuir M, Fraser S, Walsh S, Andrew N, Leung HY. A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer. BMC cancer. 2016; 16: 529
Munkley J, Vodak D, Livermore KE, James K, Wilson BT, Knight B, McCullagh P, McGrath J, Crundwell M, Harries LW, Leung HY, Robson CN, Mills IG, Rajan P, Elliott DJ Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability. EBioMedicine. 2016; 8: 103-16
Myers SM, Bawn RH, Bisset LC, Blackburn TJ, Cottyn B, Molyneux L, Wong AC, Cano C, Clegg W, Harrington RW, Leung H, Rigoreau L, Vidot S, Golding BT, Griffin RJ, Hammonds T, Newell DR, Hardcastle IR. High-throughput screening and hit validation of extracellular-related kinase 5 (ERK5) inhibitors. ACS Comb Sci. 2016; 18: 444-55
Peck B, Schug ZT, Zhang Q, Dankworth B, Jones DT, Smethurst E, Patel R, Mason S, Jiang M, Saunders R, Howell M, Mitter R, Spencer-Dene B, Stamp G, McGarry L, James D, Shanks E, Aboagye EO, Critchlow SE, Leung HY Harris AL, Wakelam MJ, Gottlieb E, Schulze A. Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments. Cancer & metabolism. 2016; 4: 6
