Trosolwg
Research overview
I am based in Prof Alan Clarke's laboratory in the European Cancer Stem Cell Research Institute. My research continues to explore and utilise genetically engineered mouse models of colorectal cancer and the therapeutic role of molecularly targeted novel anti-cancer agents against PI3K/mTOR and RAS/RAF/MEK/ERK signaling. This work complements the recognised strengths in personalised medicine (Stratified Medicine Programme, CRUK) and cancer genetics at Cardiff University. This research is now being extended to incorporate small animal PET imaging and novel tracer agents as predictive biomarkers of response to tailored anti-cancer agents (NISCHR funding, £217K over 2 years). I have recently secured funding from Cardiff CRUK Experimental Cancer Medicine Centre, to support a full-time research assistant in Prof. Trevor Dales' laboratory to develop colorectal cancer organoids as an 'ex vivo' model system. A Cancer Research Wales PhD Studentship will further this work from October 2013. I am planning to extend this technique to include other solid tumours in particular lung cancer. Given the direction of my clinical work I am also seeking funding opportunities locally to develop a genetically engineered mouse model of lung cancer.
I am currently funded by NISCHR for research sessions, prior to this I was a Walport Clinical Lecturer and CRUK Bobby Moore Clinical Research Fellow.
Cyhoeddiadau
2020
- Walls, G. M.et al. 2020. CONCORDE: A phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer. Clinical and Translational Radiation Oncology 25, pp. 61-66. (10.1016/j.ctro.2020.09.006)
- Shaw, P.et al. 2020. Flip-flop oesophageal movement during radical radiotherapy for oesophageal malignancy. Clinical Oncology 32(10), pp. e214-e215. (10.1016/j.clon.2020.06.005)
- Middleton, G.et al. 2020. Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Lancet Respiratory Medicine 8(9), pp. 895-904. (10.1016/S2213-2600(20)30033-3)
- Badder, L. M.et al. 2020. 3D imaging of colorectal cancer organoids identifies responses to Tankyrase inhibitors. PLoS ONE 15(8), article number: e0235319. (10.1371/journal.pone.0235319)
- Shakir, R.et al. 2020. Patterns and predictors of relapse following radical chemoradiation therapy delivered using intensity modulated radiation therapy with a simultaneous integrated boost in anal squamous cell carcinoma. International Journal of Radiation Oncology - Biology - Physics 106(2), pp. 329-339. (10.1016/j.ijrobp.2019.10.016)
2017
- Daly, C. S.et al. 2017. Functional redundancy between Apc and Apc2 regulates tissue homeostasis and prevents tumorigenesis in murine mammary epithelium. Oncogene 36(13) (10.1038/onc.2016.342)
2015
- Raja, M.et al. 2015. Assessment of the in vivo activity of PI3K and MEK inhibitors in genetically defined models of colorectal cancer. Molecular Cancer Therapeutics 14(10), pp. 2175-2186. (10.1158/1535-7163.MCT-15-0223)
2014
- Tanguay, J. S.et al. 2014. Limited stage small cell lung cancer (LS SCLC) South East Wales experience. Lung Cancer 88(Supp 1), pp. S66. (10.1016/S0169-5002(14)70180-1)
2011
- Shaw, P. and Adams, R. A. 2011. Where now for anti-EGF receptor therapies in colorectal cancer?. Expert Review of Anticancer Therapy 11(10), pp. 1543-1553. (10.1586/era.11.143)
- Shaw, P., Maughan, T. S. and Clarke, A. R. 2011. Dual inhibition of epidermal growth factor and insulin-like 1 growth factor receptors reduce intestinal adenoma burden in the Apcmin/+ mouse. British Journal of Cancer 105(5), pp. 649-657. (10.1038/bjc.2011.291)
2007
- Shaw, P. H. S.et al. 2007. A clinical review of the investigation and management of carcinoma of unknown primary in a single cancer network. Clinical Oncology 19(1), pp. 87-95. (10.1016/j.clon.2006.09.009)
- Shaw, P. and Clarke, A. R. 2007. Murine models of intestinal cancer: Recent advances. DNA Repair 6(10), pp. 1403-1412. (10.1016/j.dnarep.2007.02.022)
2004
- Shaw, P. and Agrawal, R. 2004. Pleurodesis for malignant pleural effusions. Cochrane Database of Systematic Reviews 2004(1), article number: CD002916. (10.1002/14651858.CD002916.pub2)
2003
- Shaw, P. and Marks, A. 2003. Malignant epidural spinal cord compression. European Journal of Palliative Care, pp. 141-144.
2001
- Shaw, P. 2001. The use of NSAIDs in patients with cancer: just how safe is it?. European Journal of Palliative Care, pp. 181-185.
1992
- McKibben, P. E.et al. 1992. Insulin is a specific stimulus to hypothalamic Neuropeptide Y: A comparison of the effects of insulin replacement and food restriction in streptozocin-diabetic rats. Peptides 13(4), pp. 721-727. (10.1016/0196-9781(92)90178-6)
My current research takes advantage of local expertise in bioscience, chemistry and the PETIC facility at Cardiff University to explore PET biomarkers of response to novel anti-cancer agents. The benefit of this approach to future patients will be the potential to optimise therapeutic benefit whilst minimising harm and economic costs. We have recently demonstrated a marked anti-tumour effect giving rise to a three fold increased in median survival as a consequence of PI3K/mTOR inhibition in a pre-clinical model of colon cancer.
The findings from this model have been used to investigate PET as a biomarker to identify antagonism of the PI3K-mTOR pathway. As cyclin D1 mRNA levels are markedly elevated in our model system, this has been used as a target biomarker in the construction of a tracer molecule capable of hybridising to Cyclin D1 via a cell entry protein (Tat). We plan to link this probe to Zerconium-89 for future PET CT studies to identify signal changes associated with therapeutic response.
We are establishing the PETCT platform using FDG and have identified FDG avidity in intestinal tumours
Affiliated staff
- Research Technician: Meera Raja (NISCHR)
- Collaborators: Prof Trevor Dale (Bioscience), Dr Stephen Paisey (PETIC), Dr James Redman (Chemistry), Dr Andrew Hollins (Bioscience)
- PhD Student: Luned Bader (October 2013)
Grants
- Co-Principal Investigator (with Prof T Dale and Prof Alan Clarke) £104,280 Cancer Research Wales PhD studentship. Developing cancer stem cell containing organoids from human primary and secondary colorectal cancers for preclinical testing of stratified ant-cancer therapeutics (Oct 2013-2016)
- Principal Investigator (with Prof A. Clarke and Dr Stephen Daniels) £217,000 National Institute for Social Care and Health Research (NISCHR). PET bio-marker imaging in response to novel targeted anti-cancer therapy in a clinically applicable mouse model of colon cancer. (Feb 2013-2015)
- Co-Principal Investigator (with Prof Trevor Dale and Alan Clarke) Post-doctoral support (two years full time) funded by CRUK Experimental Cancer Medicine Centre, Cardiff. Title: Developing stem-cell containing organoids for preclinical studies of colorectal cancer therapeutics. (October 2012-2014).
- Co-Investigator (Principal Investigator Prof John Chester) £5K Cardiff CRUK Cancer Centre Development fund. Correlation of functional imaging (PET-CT) and molecular biomarkers of response to chemo-radiotherapy in head and neck cancers (2012-2013)
- Principal Investigator (with Dr Nader Omidvar, Dept Haematology, UHW) £5K Cardiff CRUK Cancer Centre, small grants bursary. Pilot study examining the therapeutic effect of a novel pvax1flipper DNA vaccine in a colon cancer mouse model. (2011-2012)
- Co-Applicant (with Prof A. Clarke) £90,000 Tenovus Charity (PhD. Studentship). Investigating PI3K/mTOR inhibition in a mouse model of colorectal cancer mutant for both Apc and Pten. (2009-2012)
- Co-Investigator (with Prof C. McGuigan/Alan Clarke) £500,000 MRC DPFS Grant. Developing new agents for colorectal cancer using genetically defined autochthonous models. (2009-2011)
- Co-Principal Investigator (with Prof Trevor Dale, Prof Alan Clarke Dr Andrew Hollins, Dr Ken Ewan and Dr Keren Paz) £6K. Extending the development of organoid technology to lung malignancy. Cardiff CRUK Centre development fund.