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.
- World-leading cancer geneticist to receive Otago’s highest honour
- Top HRC medal to Parry Guilford
- Hercus Medal to Parry Guilford
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.
- CDH1 and HDGC: the key facts
- Genetic mutation behind inherited stomach cancer (Parry Guilford is interviewed by Robyn Williams on RN The Science Show, ABC Australia website, 5 mins)
- Inherited and environmental cancer risk
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.
Publications
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
Decourtye-Espiard, L., & Guilford, P. (2023). Hereditary diffuse gastric cancer. Gastroenterology. Advance online publication. doi: 10.1053/j.gastro.2023.01.038
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
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
Fitzgerald, S., Blenkiron, C., Somers-Edgar, T., Rolfe, G., Rykers, A., Stephens, R., … Jackson, C., Cocadiz, J. A., Zou, D., Eccles, M., Day, R., Guilford, P., … Print, C. (2022, August). Evolving genomic complexity unveiled in ctDNA analysis of melanoma patients. Verbal presentation at the Cancer Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.
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
Single, A., Beetham, H., Telford, B. J., Guilford, P., & Chen, A. (2015). A comparison of real-time and endpoint cell viability assays for improved synthetic lethal drug validation. Journal of Biomolecular Screening, 20(10), 1286-1293. doi: 10.1177/1087057115605765
Journal - Research Article
Telford, B. J., Chen, A., Beetham, H., Frick, J., Brew, T. P., Gould, C. M., Single, A., Godwin, T., … Guilford, P. (2015). Synthetic lethal screens identify vulnerabilities in GPCR signalling and cytoskeletal organization in E-cadherin-deficient cells. Molecular Cancer Therapeutics, 14(5), 1213-1223. doi: 10.1158/1535-7163.mct-14-1092
Journal - Research Article
van der Post, R. S., Vogelaar, I. P., Carneiro, F., Guilford, P., Huntsman, D., Hoogerbrugge, N., … Fitzgerald, R. C. (2015). Hereditary diffuse gastric cancer: Updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. Journal of Medical Genetics, 52, 361-374. doi: 10.1136/jmedgenet-2015-103094
Journal - Research Article
Chen, A., Beetham, H., Black, M. A., Priya, R., Telford, B. J., Guest, J., Wiggins, G. A. R., Godwin, T. D., … Guilford, P. J. (2014). E-cadherin loss alters cytoskeletal organization and adhesion in non-malignant breast cells but is insufficient to induce an epithelial-mesenchymal transition. BMC Cancer, 14, 552. doi: 10.1186/1471-2407-14-552
Journal - Research Article
Willson, J. S. B., Godwin, T. D., Wiggins, G. A. R., Guilford, P. J., & McCall, J. L. (2013). Primary hepatocellular neoplasms in a MODY3 family with a novel HNF1A germline mutation. Journal of Hepatology, 59(4), 904-907. doi: 10.1016/j.jhep.2013.05.024
Journal - Research Article
Evans, J. J., Chitcholtan, K., Dann, J. M., Guilford, P., Harris, G., Lewis, L. K., Nagase, J., … Sykes, P. H. (2012). Adrenomedullin interacts with VEGF in endometrial cancer and has varied modulation in tumours of different grades. Gynecologic Oncology, 125(1), 214-219. doi: 10.1016/j.ygyno.2011.12.429
Journal - Research Article
Huang, R. Y.-J., Guilford, P., & Thiery, J. P. (2012). Early events in cell adhesion and polarity during epithelial-mesenchymal transition. Journal of Cell Science, 125(19), 4417-4422. doi: 10.1242/jcs.099697
Journal - Research Article
O'Sullivan, P., Sharples, K., Dalphin, M., Davidson, P., Gilling, P., Cambridge, L., … Luxmanan, C., … Yoon, H.-S., … Guilford, P. J. (2012). A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria. Journal of Urology, 188(3), 741-747. doi: 10.1016/j.juro.2012.05.003
Journal - Research Article
Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., … on behalf of the International Gastric Cancer Linkage Consortium. (2010). Hereditary diffuse gastric cancer: Updated consensus guidelines for clinical management and directions for future research. Journal of Medical Genetics, 47(7), 436-444. doi: 10.1136/jmg.2009.074237
Journal - Research Article
Guilford, P., Humar, B., & Blair, V. (2010). Hereditary diffuse gastric cancer: Translation of CDH1 germline mutations into clinical practice. Gastric Cancer, 13(1), 1-10. doi: 10.1007/s10120-009-0531-x
Journal - Research Article
Guise, C. P., Abbattista, M. R., Singleton, R. S., Holford, S. D., Connolly, J., Dachs, G. U., Fox, S. B., Pollock, R., Harvey, J., Guilford, P., … Patterson, A. V. (2010). The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Research, 70(4), 1573-1584. doi: 10.1158/0008-5472.CAN-09-3237
Journal - Research Article
Mai, P. L., Friedlander, M., Tucker, K., Phillips, K.-A., Hogg, D., Jewett, M. A. S., … Guilford, P., … Greene, M. H. (2010). The International Testicular Cancer Linkage Consortium: A clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred. Urologic Oncology, 28(5), 492-499. doi: 10.1016/j.urolonc.2008.10.004
Journal - Research Article
Nasri, S., Anjomshoaa, A., Song, S., Guilford, P., McNoe, L., Black, M., Phillips, V., Reeve, A., & Humar, B. (2010). Oligonucleotide array outperforms SNP array on formalin-fixed paraffin-embedded clinical samples. Cancer Genetics & Cytogenetics, 198(1), 1-6. doi: 10.1016/j.cancergencyto.2009.12.002
Journal - Research Article
Humar, B., Blair, V., Charlton, A., More, H., Martin, I., & Guilford, P. (2009). E-cadherin deficiency initiates gastric signet-ring cell carcinoma in mice and man. Cancer Research, 69(5), 2050-2056.
Journal - Research Article
Zou, D., Yoon, H.-S., Anjomshoaa, A., Perez, D., Fukuzawa, R., Guilford, P., & Humar, B. (2009). Increased levels of active c-Src distinguish invasive from in situ lobular lesions. Breast Cancer Research, 11(4), R45. doi: 10.1186/bcr2332
Journal - Research Article
Zou, D., Yoon, H.-S., Perez, D., Weeks, R. J., Guilford, P., & Humar, B. (2009). Epigenetic silencing in non-neoplastic epithelia identifies E-cadherin (CDH1) as a target for chemoprevention of lobular neoplasia. Journal of Pathology, 218(2), 265-272. doi: 10.1002/path.2541
Journal - Research Article
Holyoake, A., O'Sullivan, P., Pollock, R., Best, T., Watanabe, J., Kajita, Y., … da Silva Tatley, F., Cambridge, L., Toro, T., … Guilford, P. (2008). Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder. Clinical Cancer Research, 14(3), 742-749. doi: 10.1158/1078-0432.CCR-07-1672
Journal - Research Article
Humar, B., & Guilford, P. (2008). Hereditary diffuse gastric cancer and lost cell polarity: A short path to cancer. Future Oncology, 4(2), 229-239.
Journal - Research Article
John, T., Black, M. A., Toro, T. T., Leader, D., Gedye, C. A., Davis, I. D., Guilford, P. J., & Cebon, J. S. (2008). Predicting clinical outcome through molecular profiling in stage III melanoma. Clinical Cancer Research, 14(16), 5173-5180.
Journal - Research Article
Kawanishi, H., Matsui, Y., Ito, M., Watanabe, J., Takahashi, T., Nishizawa, K., … Guilford, P., Reeve, A., … Ogawa, O. (2008). Secreted CXCL1 is a potential mediator and marker of the tumor invasion of bladder cancer. Clinical Cancer Research, 14(9), 2579-2587. doi: 10.1158/1078-0432.CCR-07-1922
Journal - Research Article
Kwak, M. K., Lee, H.-J., Hur, K., Park, D. J., Lee, H. S., Kim, W. H., … Guilford, P., & Yang, H.-K. (2008). Expression of Krüppel-like factor 5 in human gastric carcinomas. Journal of Cancer Research & Clinical Oncology, 134(2), 163-167. doi: 10.1007/s00432-007-0265-2
Journal - Research Article
Linger, R., Dudakia, D., Huddart, R., Tucker, K., Friedlander, M., Phillips, K.-A., … Guilford, P., … Rapley, E. A. (2008). Analysis of the DND I gene in men with sporadic and familial testicular germ cell tumors. Genes Chromosomes & Cancer, 47(3), 247-252. doi: 10.1002/gcc.20526
Journal - Research Article
Nasri, S., More, H., Graziano, F., Ruzzo, A., Wilson, E., Dunbier, A., McKinney, C., Merriman, T., Guilford, P., … Humar, B. (2008). A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: A case control study in an Italian population. BMC Cancer, 8, 138. doi: 10.1186/1471-2407-8-138
Journal - Research Article
Guilford, P., Blair, V., More, H., & Humar, B. (2007). A short guide to hereditary diffuse gastric cancer. Hereditary Cancer in Clinical Practice, 5(4), 183-194.
Journal - Research Article
Humar, B., Fukuzawa, R., Blair, V., Dunbier, A., More, H., Charlton, A., … Reeve, A. E., … Guilford, P. (2007). Destabilized adhesion in the gastric proliferative zone and c-Src kinase activation mark the development of early diffuse gastric cancer. Cancer Research, 67(6), 2480-2489. doi: 10.1158/0008-5472.CAN-06-3021
Journal - Research Article
