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Otago Medical School staff profiles

Dr Cath Drummond

PositionResearch Fellow
DepartmentDepartment of Pathology (Dunedin)
QualificationsBSc(Hons) PhD
Research summaryOncogenic variants of the p53 tumour suppressor
Memberships
  • Associate Member, American Association for Cancer Research 2016 to present
  • Associate Investigator, Maurice Wilkins Centre for Molecular Discovery (MWC) 2019 to present

Research

My research is focussed on understanding how oncogenic variants of the p53 tumour suppressor drive cancer progression as well as identifying ways to target these variants therapeutically. This is centered around two main areas.

  1. Identifying small molecule inhibitors of p53 variants. Despite oncogenic p53 variants being reported in multiple tumour types, there are no known inhibitors of p53 variants. In addition, little is known about their regulation and therefore how to inhibit their activity. I am currently developing a cell based screening assay to identify inhibitors of p53 variants. This assay will allow us to easily screen small molecules libraries against p53 variants and identify hit compounds for new drug discovery initiatives. This research is funded by the Cancer Society of New Zealand.
  2. Determining the role of p53 variants in drug tolerance. Although responses to targeted therapeutics (kinase inhibitors) are initially dramatic, these responses are often short lived and relapse is inevitable. This is because some cells within the tumour switch to a drug tolerant state which allows them to initially survive treatment and develop resistance. Together with Dr Glen Reid, I am using melanoma and lung cancer models to investigate whether oncogenic p53 variants are involved in the switch to drug tolerance. This research is funded by a recently awarded Marsden Project Grant.

Additional details

There are several research projects available and interested students are encouraged to make contact to discuss options.

  1. Project Title: Drivers of tolerance to TKIs in lung cancer and melanoma. Level: PhD
  2. Project Title: Using CRISPR to tag tumour suppressor gene isoforms in malignant melanoma. Level: PhD

Publications

Eiholzer, R. A., Mehta, S., Kazantseva, M., Drummond, C. J., McKinney, C., Young, K., … Fleming, N., Morrin, H. R., Reader, K., Royds, J. A., Landmann, M., Petrich, S., … Taha, A., Hung, N. A., Slatter, T. L., & Braithwaite, A. W. (2020). Intronic TP53 polymorphisms are associated with increased Δ133TP53 transcript, immune infiltration and cancer risk. Cancers, 12(9), 2472. doi: 10.3390/cancers12092472

Kazantseva, M., Mehta, S., Eiholzer, R. A., Gimenez, G., Bowie, S., Campbell, H., Reily-Bell, A. L., … Ray, S., Drummond, C. J., Reid, G., … Wiles, A., Morrin, H. R., Reader, K. L., Hung, N. A., Baird, M. A., Slatter, T. L., & Braithwaite, A. W. (2019). The Δ133p53β isoform promotes an immunosuppressive environment leading to aggressive prostate cancer. Cell Death & Disease, 10, 631. doi: 10.1038/s41419-019-1861-1

Ladds, M. J. G. W., van Leeuwen, I. M. M., Drummond, C. J., Chu, S., Healy, A. R., Popova, G., … Laín, S. (2018). A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage. Nature Communications, 9(1), 1107. doi: 10.1038/s41467-018-03441-3

Drummond, C. J., Hanna, J. A., García, M. R., Devine, D. J., Heyrana, A. J., Finkelstein, D., … Hatley, M. E. (2018). Hedgehog pathway drives fusion-negative rhabdomyosarcoma initiated from non-myogenic endothelial progenitors. Cancer Cell, 33(1), 108-124. doi: 10.1016/j.ccell.2017.12.001

Ladds, M. J. G. W., Pastor-Fernández, A., Popova, G., van Leeuwen, I. M. M., Eng, K. E., Drummond, C. J., … Laín, S. (2018). Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib. PLoS ONE, 13(4), e0195956. doi: 10.1371/journal.pone.0195956

Journal - Research Article

Eiholzer, R. A., Mehta, S., Kazantseva, M., Drummond, C. J., McKinney, C., Young, K., … Fleming, N., Morrin, H. R., Reader, K., Royds, J. A., Landmann, M., Petrich, S., … Taha, A., Hung, N. A., Slatter, T. L., & Braithwaite, A. W. (2020). Intronic TP53 polymorphisms are associated with increased Δ133TP53 transcript, immune infiltration and cancer risk. Cancers, 12(9), 2472. doi: 10.3390/cancers12092472

Kazantseva, M., Mehta, S., Eiholzer, R. A., Gimenez, G., Bowie, S., Campbell, H., Reily-Bell, A. L., … Ray, S., Drummond, C. J., Reid, G., … Wiles, A., Morrin, H. R., Reader, K. L., Hung, N. A., Baird, M. A., Slatter, T. L., & Braithwaite, A. W. (2019). The Δ133p53β isoform promotes an immunosuppressive environment leading to aggressive prostate cancer. Cell Death & Disease, 10, 631. doi: 10.1038/s41419-019-1861-1

Ladds, M. J. G. W., van Leeuwen, I. M. M., Drummond, C. J., Chu, S., Healy, A. R., Popova, G., … Laín, S. (2018). A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage. Nature Communications, 9(1), 1107. doi: 10.1038/s41467-018-03441-3

Ladds, M. J. G. W., Pastor-Fernández, A., Popova, G., van Leeuwen, I. M. M., Eng, K. E., Drummond, C. J., … Laín, S. (2018). Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib. PLoS ONE, 13(4), e0195956. doi: 10.1371/journal.pone.0195956

Drummond, C. J., Hanna, J. A., García, M. R., Devine, D. J., Heyrana, A. J., Finkelstein, D., … Hatley, M. E. (2018). Hedgehog pathway drives fusion-negative rhabdomyosarcoma initiated from non-myogenic endothelial progenitors. Cancer Cell, 33(1), 108-124. doi: 10.1016/j.ccell.2017.12.001

Hanna, J. A., Drummond, C. J., Garcia, M. R., Go, J. C., Finkelstein, D., Rehg, J. E., & Hatley, M. E. (2017). Biallelic Dicer1 loss mediated by aP2-Cre drives angiosarcoma. Cancer Research, 77(22), 6109-6118. doi: 10.1158/0008-5472.Can-17-1262

Drummond, C. J., Esfandiari, A., Liu, J., Lu, X., Hutton, C., Jackson, J., … Lunec, J. (2016). TP53 mutant MDM2-amplified cell lines selected for resistance to MDM2-p53 binding antagonists retain sensitivity to ionizing radiation. Oncotarget, 7(29), 46203-46218. doi: 10.18632/oncotarget.10073

Sachweh, M. C. C., Stafford, W. C., Drummond, C. J., McCarthy, A. R., Higgins, M., Campbell, J., … Laín, S. (2015). Redox effects and cytotoxic profiles of MJ25 and auranofin towards malignant melanoma cells. Oncotarget, 6(18), 16488-16506. doi: 10.18632/oncotarget.4108

Darekar, S. D., Mushtaq, M., Gurrapu, S., Kovalevska, L., Drummond, C., Petruchek, M., … Kashuba, E. (2015). Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts. Oncotarget, 6(25), 21016-21028. doi: 10.18632/oncotarget.4123

Sachweh, M. C. C., Drummond, C. J., Higgins, M., Campbell, J., & Laín, S. (2013). Incompatible effects of p53 and HDAC inhibition on p21 expression and cell cycle progression. Cell Death & Disease, 4(3), e533. doi: 10.1038/cddis.2013.61

McCarthy, A. R., Sachweh, M. C. C., Higgins, M., Campbell, J., Drummond, C. J., van Leeuwen, I. M. M., … Laín, S. (2013). Tenovin-D3, a novel small-molecule inhibitor of sirtuin SirT2, increases p21 (CDKN1A) expression in a p53-independent manner. Molecular Cancer Therapeutics, 12(4), 352-360. doi: 10.1158/1535-7163.MCT-12-0900

Watson, A. F., Liu, J., Bennaceur, K., Drummond, C. J., Endicott, J. A., Golding, B. T., … Hardcastle, I. R. (2011). MDM2-p53 protein-protein interaction inhibitors: A-ring substituted isoindolinones. Bioorganic & Medicinal Chemistry Letters, 21(19), 5916-5919. doi: 10.1016/j.bmcl.2011.07.084

Hardcastle, I. R., Liu, J., Valeur, E., Watson, A., Ahmed, S. U., Blackburn, T. J., … Drummond, C., … Lunec, J. (2011). Isoindolinone inhibitors of the murine double minute 2 (MFM2)-p53 protein-protein interaction: Structure-activity studies leading to improved potency. Journal of Medicinal Chemistry, 54(5), 1233-1243. doi: 10.1021/jm1011929

Woon, S.-T., Reddy, C. B., Drummond, C. J., Schooltink, M. A., Baguley, B. C., Kieda, C., & Ching, L.-M. (2005). A comparison of the ability of DMXAA and xanthenone analogues to activate NF-κB in murine and human cell lines. Oncology Research, 15(7-8), 351-364.

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Journal - Research Other

Drummond, C. J., & Hatley, M. E. (2018). A case of mistaken identity: Rhabdomyosarcoma development from endothelial progenitor cells. Molecular & Cellular Oncology, 5(4), e1448246. doi: 10.1080/23723556.2018.1448246

Drummond, C. J., Finlay, G. J., Broome, L., Marshall, E. S., Richardson, E., & Baguley, B. C. (2011). Action of SN 28049, a new DNA binding topoisomerase II-directed antitumour drug: Comparison with doxorubicin and etoposide [Short report]. Investigational New Drugs, 29(5), 1102-1110. doi: 10.1007/s10637-010-9473-8

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