Professor Timothy P. Hughes, MD, FRACP, FRCPA, MBBS, FAAHMS
Professor Timothy Hughes is the Cancer Theme Leader at SAHMRI and Consultant Haematologist in the Division of Haematology at SA Pathology. He is also Chair of the International Chronic Myeloid Leukemia Foundation (iCMLf); Fellow of the Australian Academy of Health and Medical Sciences (AAHMS) and Beat Cancer Professor, University of Adelaide.
Professor Hughes is an international expert in the biology and treatment of leukaemia. He led the establishment of the molecular response criteria that are used world-wide to measure response in chronic myeloid leukaemia (CML) and has led many of the key Global and National trials. His group has successfully developed predictive bioassays that influence the way CML patients are managed world-wide. He has published over 250 papers that have been cited over 28,000 times.
20 Most Significant Publications
- Branford S, Rudzki Z, Walsh S, Grigg A, Arthur C, Taylor K, Herrmann R, Lynch KP, Hughes TP. High Frequency of Point Mutations Clustered Within the ATP Binding Region of BCR/ABL in CML and Ph-positive ALL Patients who Develop Imatinib (STI571) Resistance. 2002 Blood 99: 3472-3475 IF 10.9: CIT 636
- O’Brien S G, Guilhot F, Larson R A, Gathmann I, Baccarani M, Cervantes F, Cornelissen J, Fischer T, Hochhaus A, Hughes TP, Lechner K, Nielsen J, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman J, Kantarjian, Taylor K, Verhoef G, Bolton A, Capdeville R, Druker B. Imatinib compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukaemia. 2003 New England Journal of Medicine 348: 994-1004. IF 52.5: CIT 2633 This highly cited paper describing the clinical results of the first randomised study of a TKI for CML therapy. I played a critical role in the trial, coordinating the global molecular monitoring.
- Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J, Taylor K, Herrmann R, Seymour J, Arthur C, Joske D, Lynch K, Hughes TP . The detection of BCR-ABL mutations in imatinib-treated CML patients is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. 2003 Blood 102: 276-283. IF 10.9: CIT 669
- Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Henslee ML, Gathmann I, Bolton AE, van Hoomissen IC, Goldman JM and Radich J. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed patients with chronic myeloid leukemia. 2003 New England Journal of Medicine 349:1421-30 IF 52.5: CIT 1089 This landmark paper was the first to define MMR and to demonstrate that achievement of MMR was predictive of a very low risk of disease progression.
- Michor F, Hughes T, Iwasa Y, Branford S, Shah N, Sawyers C, Nowak A. Dynamics of chronic myeloid leukaemia. 2005 Nature (A*) 435(7046):1267-70 June 30 IF 29.3: CIT 548 The first mathematical model of a human cancer predicted that leukaemic stem cells may not be reduced by imatinib. The primary data used for this mathematical model was produced in our lab.
- Hughes TP , Deininger MW, Hochhaus A, Branford S, Radich JP, Kaeda J, Baccarani M, Cortes J, Cross NC, Druker BJ, Gabert J, Grimwade JH, Longtine J, Martinelli G, Saglio G, Soverini S, Stock W, Goldman J. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors – Review and recommendations for ‘harmonizing’ current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. 2006 Blood (A*) 108(1):28-37 IF 10.9: CIT 824 I led the global move to standardise PCR measurement of MRD in CML.
- Druker B, Guilhot F, O’Brien S, Gathman I, Kantasrjian H, Gattermann N, Deininger M, Silver R, Goldman J, Stone R, Cervantes F, Hochhaus A, Powell B, Gabrilove J, Rousselot P, Reiffers J, Cornelissen J, Hughes TP , Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen J, Radich J, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson R. Five-year follow up of patients receiving Imatinib for chronic myeloid leukaemia. 2006 New England Journal of Medicine (A*) 355:2407-17. IF 52.5 CIT 2260
- Mullighan CG, Miller CB, Radtke I, Phillips LA, Dalton J, Ma J, White D, Hughes TP, Le Beau MM, Pui C_H, Relling MV, Shurtleleff SA, Downing JR. BCR-ABL1 lymphoblastic leukaemia is characterised by the deletion of Ikaros. 2008 Nature (A*) 453(7191):110-4IF 28.8 CIT 480
- Hughes TP, Branford S White DL, Reynolds J, Koelmeyer, Seymour JF, Taylor K, Arthur C, Schwarer A, Morton J, Cooney J, Leahy MF, Rowling P, Catalano J, Hertzberg M, Filshie R, Mills AK, Fay K, Durrant S, Januszewicz, Joske D, Underhill C, Dunkley S, Lynch K, Grigg A on behalf of the Australasian Leukaemia and Lymphoma Group. Impact of early dose intensity on cytogenetic and molecular responses in chronic phase CML patients receiving 600 mg/day. 2008 Blood (A*) 112(10):3965-3973 IF 10.9 CIT 113
- Viswanathan S, Powers JT, Einhorn W, Hoshida Yujin, Ng T, Toffanin S, O’Sullivan M, Lu J, Philips LA, Lockhart VL, Shah SP, Tanwar PS, Mermel CH, Beroukhim R, Azam M, Teixeira J, Meyerson M, Hughes TP, Llovet JM, Radich J, Mullighan CG, Golub TR, Sorensen PH, Daley GQ. Lin28 enhances tumorigenesis and is associated with advanced human malignancies. 2009 Nature Genetics (A*) 41(7): 843-8 IF: 34.3 CIT 333
- Hughes TP , Saglio G, Branford S, Soverini S, Kim D-W, Muller MC, Martinelli G, Cortes J, Beppu L, Gottardi E, Kim D, Erben P, Shou Y, Haque A, Gallagher N, Radich J, Hochhaus A. Impact of baseline BCR-ABL mutations on response to Nilotinib in patients with chronic myeloid leukaemia in chronic phase. 2009 Journal of Clinical Oncology (A*) 27:(25) 4204-10 IF: 17.8 CIT 188 JCO is the premium oncology journal. I led the international panel that reviewed the mutation data from this trial to identify a limited number of mutations as resistant to nilotinib.
- Cortes JE, Baccarani M, Guilhot F, Druker BJ, Branford S, Kim D-W, Pane F, Pasquini R, Goldberg SL, Kalaycio M, Moiraghi B, Rowe JM, Tothova, De Souza C, Rudoltz M, Yu R, Krahnke T, Kantarjian HM, Radich JP, Hughes TP . Phase III randomized open label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukaemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study. 2010 Journal of Clinical Oncology (A*) 28(3):424-430. IF: 17.8 CIT 175
- Saglio G, Kim D-W, Issaragrisil S, Le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM the ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukaemia. N. Engl J Med (A*) 2010 362:2251-2259 IF: 47.1 CIT 796 First demonstration that nilotinib achieved deeper earlier molecular responses. I was one of 5 global leaders for this study.
- White DL, Dang P, Engler J, Frede A, Zrim S, Osborn M, Saunders VA, Manley PW, Hughes TP. Functional activity of the OCT-1 protein is predictive of long-term outcome in patients with chronic-phase chronic myeloid leukaemia treated with imatinib. J Clin Oncol (A*) 2010 28:2761-2767 IF: 17.8 CIT 105
- Hughes TP, Hochhaus A, Branford S, Muller MC, Kaeda J, Foroni L, Druker B, Guilhot F, Larson RA, O’Brien SG, Rudoltz MS, Mone M, Wehrle E, Modur V, Goldman JM, Radich JP. Long term prognostic significance of early molecular response to imatinib in new diagnosed chronic myeloid leukaemia: an analysis from the international randomized study of interferon versus STI571 (IRIS). Blood (A*) 2010 116:3758-3765 IF 10.9 CIT 287 Demonstrated that specific levels of BCR-ABL predicted event free survival. This formed the basis of the next ELN recommendations for CML therapy.
- Parker W, Prime J, Ho M, Irwin DL, Scott H, Hughes TP, Branford S. Sensitive detection of BCR-ABL1 mutations in patients with chronic myeloid leukaemia after imatinib resistance is predictive of outcome during subsequent therapy. 2011 Journal of Clinical Oncology 29(32)4250-4259 IF 18.9 CIT 38
- Kantarjian HM, Hochhaus A, Saglio G, Souza CD, Flinn IW, Stenke L, Goh YT, Rosti G, Nakamae H, Gallagher NJ, Hoenekopp A, Blakesley RE, Larson RA, Hughes TP. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24 month minimum follow up of the phase-3 randomised ENESTnd trial. Lancet Oncology 2011 12(9):841-51 IF 18.7 CIT 208
- Branford S, Yeung DT, Prime JA, Choi S-Y, Bang J-H, Park JE, Kim D-W, Ross DM, Hughes TP . BCR-ABL1 doubling-times more reliably assess the dynamics of CML relapse compared with the BCR-ABL1 fold-rise: implications for monitoring and management. 2012 Blood 119:4264-4271 IF 10.6 CIT 10
- Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Müller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes TP, Goldman JM, Shah NP, Kantarjian H; PACE Investigators. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013 Nov: 369(19):1783-1796 IF 47.1 CIT 3
- Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Yeung DT, Dang P, Goyne JM, Slader C, Filshie RJ, Mills AK, Melo JV, White DL, Grigg AP, Hughes TP . Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013 Jul 25;122(4): 515-522.IF 10.6 CIT 67