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Understanding and utilising cancer gene expression

Professor Guilford's work with both a fatal form of inherited stomach cancer, and bladder cancer, has seen the development of diagnostic tools that have profound effects on saving lives.

In 2017 his work has been recognised as recipient of the Distinguished Research Medal, the University of Otago's highest research honour. Previously his work has also been recognised by the award of the top Health Research Council of New Zealand medal; the Beaven Medal, for his contribution to translational research, and the Royal Society of New Zealand's Sir Charles Hercus Medal for biomedical sciences.

This work also has implications for diagnostic tools for prostate, ovarian, cervical and uterine cancer.

"By understanding the exact differences between any given patient's cancer and normal tissue, we have a powerful starting point for designing drugs that will kill cancer cells but not healthy cells. This will lead to better treatments and fewer side effects."

Professor Guilford is a Principal Investigator in the Cancer Genetics Laboratory, and co-founder and Chief Scientific Officer of Pacific Edge Ltd.

Pacific Edge specialises in the discovery and commercialisation of diagnostic and prognostic technology for the early detection and monitoring of cancer. Professor Guilford is also senior inventor on Pacific Edge patents including its flagship bladder cancer diagnostic test Cxbladder®.

Bladder cancer diagnostics breakthrough

Professor Guilford's work has been integral in the development of Cxbladder®. This is a clinically validated urine test that measures the gene expression levels of five biomarkers in order to diagnose bladder cancer. This product has recently won the NZ Innovation Awards and has secured significant contracts with healthcare providers in NZ and the USA.

Inherited stomach cancer

Professor Guilford's work in understanding the role of mutations in the CDH1 gene in familial gastric cancer and the subsequent development of a genetic test, has dramatically decreased the mortality from this form of inherited cancer.

Tumours develop by acquiring mutations in genes that control cell proliferation, survival and migration. Although these mutations help the development of the cancer cells, they can also create weaknesses. Professor Guilford and his team are working to find those weaknesses and develop drugs that exploit them.

Multiple vulnerabilities have been identified in cancers with mutations in the tumour suppressor gene CDH1. Drugs that exploit some of these vulnerabilities have already been identified and are being rapidly progressed towards the treatment of common forms of breast and stomach cancer. This successful strategy is now being applied to common mutations in colorectal cancer.

Parry Guilford
Professor Parry Guilford

Qualifications

  • MSc Otago 1983
  • PhD Cambridge 1989

Awards and achievements

  • Deputy Director of Healthier Lives
  • University of Otago Distinguished Research Medal 2017
  • RSNZ Sir Charles Hercus Medal 2014, for biomedical sciences
  • Beaven Medal 2014, the top HRC medal for contribution to translational research
  • James Cook Fellowship 2010
  • Member of NZ Health Research Council's College of Experts 2011
  • Richard Gelb Award: IV Gastric Cancer Congress, New York 2001, for contribution to the understanding of the biology of gastric cancer
  • British Journal of Surgery Lecture, Royal College of Surgeons, London, November 2007
  • Collected publications have been cited over 4,400 times

Life saver

2017 Distinguished Research Medal winner Professor Parry Guildford can count among his many achievements the discovery of the first-known gene for inherited gastric cancer and the development of a simple-to-use non-invasive test for bladder cancer.

Parry Guilford thumbnail
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Publications

Buckley, K. H., Tondon, R., Guilford, P., & Katona, B. W. (2023). Non-targeted biopsies in hereditary diffuse gastric cancer: Necessary, but not enough. Translational Cancer Research, 12(7), 1883-1886. doi: 10.21037/tcr-23-541
Journal - Research Other
Fitzgerald, S., Blenkiron, C., Stephens, R., Mathy, J. A., Somers-Edgar, T., Rolfe, G., … Jackson, C., Eccles, M., … Rodger, E., … Guilford, P., … Print, C. G. (2023). Dynamic ctDNA mutational complexity in patients with melanoma receiving immunotherapy. Molecular Diagnosis & Therapy. Advance online publication. doi: 10.1007/s40291-023-00651-4
Journal - Research Article
Decourtye-Espiard, L., & Guilford, P. (2023). Hereditary diffuse gastric cancer. Gastroenterology. Advance online publication. doi: 10.1053/j.gastro.2023.01.038
Journal - Research Other
Hughes, M., Brew, T., Black, M., & Guilford, P. (2022). Single-cell RNA sequencing reveals potential synthetic lethal targets for chemoprevention of hereditary diffuse gastric cancer. Proceedings of the Genetics Otago (GO) Annual Symposium. Retrieved from https://blogs.otago.ac.nz/go
Conference Contribution - Published proceedings: Abstract
Redpath, K. J., Bougen-Zhukov, N., Black, M. A., & Guilford, P. J. (2022). Identification and development of novel drug combinations for diffuse gastric cancer. Proceedings of the Genetics Otago (GO) Annual Symposium. Retrieved from https://blogs.otago.ac.nz/go
Conference Contribution - Published proceedings: Abstract
Gullo, I., Oliveira, C., van der Post, R. S., van Dieren, J. M., Davis, J. L., Bougen-Zhukov, N., Guilford, P., & Carneiro, F. (2021). Updated perspective and directions on hereditary diffuse gastric cancer. In B. Jenkins (Ed.), Research and clinical applications of targeting gastric neoplasms. (pp. 217-258). London, UK: Elsevier. doi: 10.1016/B978-0-323-85563-1.00011-3
Chapter in Book - Research
Dunbier, A. K., & Guilford, P. J. (2002). Gastric cancer: Inherited predisposition. In J. R. Bertino (Ed.), Encyclopedia of cancer. (2nd ed.) (pp. 253-258). Academic Press. [Encyclopaedia/Dictionary Entry].
Chapter in Book - Research
Dunbier, A. K., & Guilford, P. J. (2002). Gastric cancer: Inherited predisposition. In S. R. Hamilton & L. A. Aaltonen (Eds.), Encyclopedia of Cancer, Volume 2. (2nd ed.) (pp. 253-258). USA: Elsevier Science.
Chapter in Book - Research
Fenoglio-Preiser, C., Carneiro, F., Correa, P., Guilford, P., & et al (2000). Gastric carcinoma. In S. R. Hamilton & L. A. Aaltonen (Eds.), World Health Organization classification of tumours: Pathology and genetics of tumours of the digestive system. (pp. 39-52). Lyon, France: IARC Press.
Chapter in Book - Research
Fitzgerald, S., Blenkiron, C., Stephens, R., Mathy, J. A., Somers-Edgar, T., Rolfe, G., … Jackson, C., Eccles, M., … Rodger, E., … Guilford, P., … Print, C. G. (2023). Dynamic ctDNA mutational complexity in patients with melanoma receiving immunotherapy. Molecular Diagnosis & Therapy. Advance online publication. doi: 10.1007/s40291-023-00651-4
Journal - Research Article
Bougen-Zhukov, N., Decourtye-Espiard, L., Mitchell, W., Redpath, K., Perkinson, J., Godwin, T., Black, M. A., & Guilford, P. (2022). E-cadherin-deficient cells are sensitive to the multikinase inhibitor dasatinib. Cancers, 14, 1609. doi: 10.3390/cancers14071609
Journal - Research Article
Brew, T., Bougen-Zhukov, N., Mitchell, W., Decourtye, L., Schulpen, E., Nouri, Y., Godwin, T., & Guilford, P. (2021). Loss of E-cadherin leads to druggable vulnerabilities in sphingolipid metabolism and vesicle trafficking. Cancers, 14(1), 102. doi: 10.3390/ cancers14010102
Journal - Research Article
Decourtye-Espiard, L., Bougen-Zhukov, N., Godwin, T., Brew, T., Schulpen, E., Black, M. A., & Guilford, P. (2021). E-cadherin-deficient epithelial cells are sensitive to HDAC inhibitors. Cancers, 14(1), 175. doi: 10.3390/ cancers14010102
Journal - Research Article
Dixon, K., Brew, T., Farnell, D., Godwin, T. D., Cheung, S., Chow, C., … Guilford, P., & Huntsman, D. G. (2021). Modelling hereditary diffuse gastric cancer initiation using transgenic mouse-derived gastric organoids and single-cell sequencing. Journal of Pathology, 254, 254-264. doi: 10.1002/path.5675
Journal - Research Article
Luxenburger, A., Bougen-Zhukov, N., Fraser, M. G., Beetham, H., Harris, L. D., Schmidt, D., … Guilford, P. J., & Evans, G. B. (2021). Discovery of AL-GDa62 as a potential synthetic lethal lead for the treatment of gastric cancer. Journal of Medicinal Chemistry, 64, 18114-18142. doi: 10.1021/acs.jmedchem.1c01609
Journal - Research Article
Brewer, N., Atkinson, J., Guilford, P., Print, C., Blakely, T., & Teng, A. (2020). An estimate of limited duration cancer prevalence in New Zealand using 'big' data. New Zealand Medical Journal, 133(1514), 49-62. Retrieved from https://www.nzma.org.nz/journal
Journal - Research Article
Chin, C. V., Antony, J., Ketharnathan, S., Labudina, A., Gimenez, G., Parsons, K. M., … Braithwaite, A., Guilford, P., … Horsfield, J. A. (2020). Cohesin mutations are synthetic lethal with stimulation of WNT signaling. eLIFE, 9, e61405. doi: 10.7554/eLife.61405
Journal - Research Article
Zou, D., Day, R., Cocadiz, J. A., Parackal, S., Mitchell, W., Black, M. A., … Jackson, C., & Guilford, P. (2020). Circulating tumor DNA is a sensitive marker for routine monitoring of treatment response in advanced colorectal cancer. Carcinogenesis, 41(11), 1507-1517. doi: 10.1093/carcin/bgaa102
Journal - Research Article
Beetham, H., Chen, A., Telford, B. J., Single, A., Jarman, K. E., Lackovic, K., … Guilford, P. (2019). A high-throughput screen to identify novel synthetic lethal compounds for the treatment of E-cadherin-deficient cells. Scientific Reports, 9, 12511. doi: 10.1038/s41598-019-48929-0
Journal - Research Article
Bougen-Zhukov, N., Nouri, Y., Godwin, T., Taylor, M., Hakkaart, C., Single, A., Brew, T., Permina, E., Chen, A., Black, M. A., & Guilford, P. (2019). Allosteric AKT inhibitors target synthetic lethal vulnerabilities in E-cadherin-deficient cells. Cancers, 11(9), 1359. doi: 10.3390/cancers11091359
Journal - Research Article
Godwin, T. D., Kelly, S. T., Brew, T. P., Bougen-Zhukov, N. M., Single, A. B., Chen, A., Stylianou, C. E., … Currie, S. K., Telford, B. J., Beetham, H. G., … Black, M. A., & Guilford, P. J. (2019). E-cadherin-deficient cells have synthetic lethal vulnerabilities in plasma membrane organisation, dynamics and function. Gastric Cancer, 22(2), 273-286. doi: 10.1007/s10120-018-0859-1
Journal - Research Article
Hakkaart, C., Ellison-Loschmann, L., Day, R., Sporle, A., Koea, J., Harawira, P., … Guilford, P. (2019). Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori. Familial Cancer, 18(1), 83-90. doi: 10.1007/s10689-018-0080-8
Journal - Research Article
Norero, E., Alarcon, M. A., Hakkaart, C., de Mayo, T., Mellado, T., Garrido, M., … Guilford, P., & Corvalan, A. H. (2019). Identification of c.1531C>T pathogenic variant in the CDH1 gene as a novel germline mutation of hereditary diffuse gastric cancer. International Journal of Molecular Sciences, 20, 4980. doi: 10.3390/ijms20204980
Journal - Research Article
Parackal, S., Zou, D., Day, R., Black, M., & Guilford, P. (2019). Comparison of Roche Cell-Free DNA collection Tubes® to Streck Cell-Free DNA BCT®s for sample stability using healthy volunteers. Practical Laboratory Medicine, 16, e00125. doi: 10.1016/j.plabm.2019.e00125
Journal - Research Article
Ellison-Loschmann, L., Sporle, A., Corbin, M., Cheng, S., Harawira, P., Gray, M., … Guilford, P., … Pearce, N. (2017). Risk of stomach cancer in Aotearoa/New Zealand: A Māori population based case-control study. PLoS ONE, 12(7), e0181581. doi: 10.1371/journal.pone.0181581
Journal - Research Article
Hoeksema, K., Wee, R., Macdonald, A., Guilford, P., Wall, J., & Cornwall, J. (2017). Where to from here? Posthumous healthcare data, digital e(lectronic)-mortality and New Zealand’s healthcare future. New Zealand Medical Journal, 130(1459), 64-70. Retrieved from http://www.nzma.org.nz/journal
Journal - Research Article
Kavalieris, L., O'Sullivan, P., Frampton, C., Guilford, P., Darling, D., Jacobson, E., … Lotan, Y. (2017). Performance characteristics of a multigene urine biomarker test for monitoring for recurrent urothelial carcinoma in a multicenter study. Journal of Urology, 197(6), 1419-1426. doi: 10.1016/j.juro.2016.12.010
Journal - Research Article
Lotan, Y., OʼSullivan, P., Raman, J. D., Shariat, S. F., Kavalieris, L., Frampton, C., Guilford, P., … Darling, D. (2017). Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma. Urologic Oncology, 35(8), 513.e15-513.e22. doi: 10.1016/j.urolonc.2017.03.008
Journal - Research Article
McInnes, T., Zou, D., Rao, D. S., Munro, F. M., Phillips, V. L., McCall, J. L., Black, M. A., Reeve, A. E., & Guilford, P. J. (2017). Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer. BMC Cancer, 17, 228. doi: 10.1186/s12885-017-3226-4
Journal - Research Article
Hansford, S., Kaurah, P., Li-Chang, H., Woo, M., Senz, J., Pinheiro, H., … Guilford, P., … Huntsman, D. G. (2015). Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncology, 1(1), 23-32. doi: 10.1001/jamaoncol.2014.168
Journal - Research Article
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