Ricky Sharma MA MB BChir FRCP FRCR PhD

Translational DNA Repair Group
Ricky Sharma’s research group focus on the translation of biochemical knowledge of DNA adducts and excision repair to the prevention and treatment of cancer.

Professor Ricky Sharma

Email 
Tel  +44 (0)1865 235209 /+44 (0)1865 617330 (PA)
PA  Sharon Draper
Email (PA) 
Contact address  Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ
Department  Department of Oncology
College Harris Manchester College

Research Summary

Research interests:
The team has developed several biomarkers for the “personalisation” of chemotherapy and radiotherapy which are being tested in clinical trials.   Laboratory studies are ongoing in parallel with clinical studies and imaging studies in the treatment of colorectal cancer and both primary and secondary liver cancer.  

In some cancers, regulatory proteins involved in repairing DNA damage may be present at abnormal levels or have altered function, impacting on how the cancer cells respond to damage induced by treatments such as radiotherapy or chemotherapy. Laboratory and clinical studies are being led by the Sharma team to characterise this altered function as a potential target for improving current cancer treatments, for example by modifying the regulation of these pathways to increase the sensitivity of cancer cells to radiation therapy to improve tumour cell kill.

Ricky Sharma’s research programme receives funding from the National Institute for Health Research (NIHR) Biomedical Research Centre Oxford, the Oxford Experimental Cancer Medicines Centre, the CRUK Oxford Centre, Cancer Research UK, the UK Medical Research Council, the Bobby Moore Fund of Cancer Research UK, the Bowel Disease Research Foundation, Sirtex Medical Ltd. and the Higher Education Funding Council for England.

Key trials
FOXFIRE is a phase III trial comparing chemotherapy alone (5-fluorouracil, oxaliplatin and folinic acid) with chemotherapy plus radio-embolisation for colorectal cancer that has spread to the liver. Radio-embolisation (also called selective internal radiotherapy or SIRT) delivers radiation directly to the cancer cells in the liver using a catheter to inject a liquid containing millions of radio-particles into the blood vessels that tumours rely on for their blood supply. The particles become trapped in and around the cancer cells, emitting very high doses of radiotherapy to achieve targeted killing of cancer cells. This novel approach minimises radiation dose to normal liver tissue and appears to have clinical benefits for patients with cancer that has spread to the liver.  This clinical trial funded by the Bobby Moore Fund of Cancer Research UK has recruited 364 participants and is in the follow-up phase until results are published in 2017.

PERFORM is a pilot study exploring the feasibility, safety and effectiveness of a novel computed tomography (CT) scanning technique called perfusion CT in patients having selective internal radiotherapy (SIRT) treatment. Standard CT is performed before and after therapy to assess how well the tumour has responded to treatment. In the PERFORM study, perfusion CT will be used to assess not only response, but also blood flow to the tumour. PERFORM aims to evaluate if the tumour perfusion pattern at baseline or shortly after the start of therapy can predict response to radio-embolisation or chemotherapy.

SONATINA is a phase II randomised trial which aims to investigate the safety and the activity of the radiosensitising drug, nelfinavir, administered before and during radiotherapy in patients with rectal carcinoma. As well as establishing the safety of this novel treatment combination for patients with rectal cancer, an additional aim of the study is testing the feasibility of a new biomarker measured in tumour tissue, Tumour Cell Density (TCD), and performing serial scans to look at blood flow (using perfusion computed tomography and dynamic contrast enhanced magnetic resonance imaging) during treatment with nelfinavir and radiotherapy.

The Rectal Imaging Trial is an observational study being performed in collaboration with Prof Fergus Gleeson, Dr Jamie Franklin and Dr Mark Anderson in the Department of Radiology, Oxford University Hospitals NHS Trust, and Prof Julia Schnabel and Dr John Fenwick in the Engineering/Physics departments of the University of Oxford.  It is funded by the Oxford Cancer Imaging Centre, of which Prof Sharma is a programme leader.  The purpose of the trial is to discover patterns of blood flow and cancer metabolism that predict a patient’s response to chemo-radiotherapy to rectal cancer using a combination of perfusion CT, dynamic contrast enhanced MRI and dynamic FdG-PET.  The trial has recruited 45 participants and aims to recruit a further 50 participants over the next 2 years.

Collaborators

Group Members

  • Dr Rebecca Carter, Postdoctoral Researcher
  • Dr Helen Winter, Clinical Research Fellow
  • Dr Azadeh Cheraghchi-Bashi-Astaneh, Research Assistant
  • Nigar Syed, Radiography Researcher
  • Dr Jamie Franklin, Clinical Research Fellow
  • Dr Tessa Greenhalgh, Clinical Research Fellow
  • George Ralli, DPhil student

Collaborators

  • Professor Fergus Gleeson, Oxford University Hospitals Trust
  • Professor Julia Schnabel, University of Oxford
  • Professor Peter Sadler, University of Warwick
  • Professor Nick La Thangue, University of Oxford
  • Professor Ian Tomlinson, University of Oxford
  • Professor Xin Lu, University of Oxford
  • Professor Rob Goldin, Imperial College, London

Biography

Ricky Sharma is the Group Leader of the Translational DNA Repair Group at the Oxford Institute for Radiation Oncology and Biology at the University of Oxford. He is also an Associate Professor at the University of Oxford, an Honorary Consultant in Clinical Oncology at the Oxford University Hospitals NHS Trust, and a Senior Research Fellow at Harris Manchester College, University of Oxford.

Ricky Sharma completed his medical training at the University of Cambridge, after which he undertook a research fellowship at the MRC Toxicology Unit at the University of Leicester leading to the award of Doctor of Philosophy. He trained in both Medical and Clinical Oncology at the University Hospitals of Leicester and the Royal Marsden Hospital, London.  Prof Sharma is a Fellow of both the Royal College of Physicians and the Royal College of Radiologists.

Ricky Sharma has a prominent national and international profile in his field.  He co-chairs the Early Phase Trials Workstream of the NCRI Clinical and Translational Radiotherapy (CTRad) Group and is the Chief Investigator of the NCRN FOXFIRE, a multi-centre, randomised clinical trial testing a new combination of chemotherapy and selective internal radiotherapy in the treatment of liver metastases from colorectal cancer.  He is an examiner for the Royal College of Radiologists (Clinical Oncology), a member of Faculty Board and a prominent member of several working groups within the college, particularly on interventional oncology and undergraduate education.  In addition to being a tutor at Harris Manchester College, University of Oxford, Prof Sharma is a module leader for postgraduate teaching of radiobiology and oncology.  He was appointed as Chair of the Teaching Committee of the Oncology Department at the University of Oxford in May 2011 and is primarily responsible for coordinating the cancer-related teaching activities at undergraduate and postgraduate level within the university department.

Current Appointments

2014 - Associate Professor, University of Oxford
2007 - Honorary Consultant in Clinical Oncology, Oxford Radcliffe Hospitals

Previous Appointments

2009 - 2014    HEFCE Clinical Senior Lecturer, University of Oxford
2006 - 2009    Senior Fellow, University of Oxford
2004 – 2006    Senior Registrar, Royal Marsden Hospital, London
2001 – 2006    Honorary Lecturer, University of Leicester
1998 – 2001    Clinical Research Fellow and Honorary Registrar, MRC Toxicology Unit and University Hospitals of Leicester

Degrees and Qualifications

2013    Fellow, Royal College of Physicians
2005    Fellow, Royal College of Radiologists
2001    Doctor of Philosophy, University of Leicester
1998    Member, Royal College of Physicians
1996    Master of Arts, University of Cambridge
1994    Bachelor of Medicine and Chirurgia, University of Cambridge
1992    Bachelor of Arts, University of Cambridge

Publications

Selected Publications
1.    Helleday T, Petermann E, Lundin C, Hodgson B, and Sharma RA (2008). DNA repair pathways as targets for cancer therapy. Nature Rev Cancer, 8: 193-204.

2.    Parsons JL, Tait PS, Finch D, Dianova IL, Edelmann MJ, Khoronenkova SV, Kessler BM, Sharma RA, McKenna WG, Dianov GL (2009).  Ubiquitin ligase ARF-BP1/Mule modulates base excision repair.  EMBO J, 28: 3207-3215.

3.    Nicolay NH, Berry DP, Sharma RA (2009).  Liver metastases from colorectal cancer: role of radio-embolization with systemic therapy.  Nature Rev Clin Oncol, 6: 687-697.

4.    Yang J, Parsons J, Nicolay NH, Caporali S, Harrington CF, Singh R, Finch D, D’Atri S, Farmer PB, Johnston PG, McKenna WG, Dianov G, Sharma RA (2010).  Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy.  Oncogene, 29: 463-468.

5.    Gottipati P, Vischioni B, Schultz N, Solomons J, Bryant HE, Djureinovic T, Issaeva N, Sleeth K, Sharma RA, Helleday T (2010).  Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells.  Cancer Res, 70: 5389-5398.

6.    Issaeva N, Thomas HD, Djureinovic T, Jaspers JE, Stoimenov I, Kyle S, Pedley N, Gottipati P, Zur R, Sleeth K, Chatzakos V, Mulligan EA, Lundin C, Gubanova E, Kersbergen A, Harris AL, Sharma RA, Rottenberg S, Curtin NJ, Helleday T (2010).  6-thioguanine selectively kills BRCA-2 defective tumors and overcomes PARP inhibitor resistance.  Cancer Res, 50: 6268-6276.

7.    dos Anjos G, Peeters M, Wyatt JC, Sharma RA (2012).  Will the medical student in the team please stand up? Lancet Oncol; 13: 757-758

8.    Hatch SB, Swift LP, Caporali S, Carter R, Hill EJ, Macgregor TP, D'Atri S, Middleton MR, McHugh PJ, Sharma RA (2013).  XPF protein levels determine sensitivity of malignant melanoma cells to oxaliplatin chemotherapy: Suitability as a biomarker for patient selection.  Int J Cancer. Epub ahead of print

9.    Sharma RA, Anthony S, Anderson EM (2013).  Clinical benefit and potential pitfalls in combining thermal ablation and radiation therapy to treat liver metastases.  J Clin Oncol. 31: e404-6.

10.    Franklin JM, Gebski V, Poston GJ, Sharma RA (2014).  Clinical trials of interventional oncology-moving from efficacy to outcomes.  Nature Rev Clin Oncol. 10.1038/nrclinonc.2014.199. [Epub ahead of print]