School of Medical Sciences


Cancer research

Principal investigator


Postgraduate students


  • Stacey D'Mello (PhD) with Dr Maggie Kalev and Professor Bruce Baguley. 
  • Herah Hansji (PhD) with Dr Marjan Askarian-Amiri and Dr Euphemia Leung
  • Debina Sarkar (PhD) with Dr Marjan Askarian-Amiri and Dr Euphemia Leung

Research


I have been a member of the research group of Professor Bruce C. Baguley. Our long-term interest has been in the development of anticancer agents. We have been particularly interested in compounds that bind to DNA by intercalation, and that subsequently poison the enzyme topoisomerase II and induce double-stranded DNA breaks. More recently we have investigated the actions of the vascular-disrupting agent, dimethylxanthenone acetic acid (DMXAA, developed in the ACSRC). This agent is believed to target vascular endothelial cells, and to suppress tumour blood flow.

The laboratory has developed a rich resource of melanoma cell lines, derived directly from patients’ tumours, and we have used these to investigate aspects of melanoma genetics, regulation, and drug responsiveness. For example, with Dr Geoffrey Charters, we showed that dysregulation of centrosome number is a characteristic feature of melanoma cells. This must contribute to the genetic instability and rapid evolution that comprise such characteristic features of melanomas.

In a project with Dr Ji Eun Kim, funded by a FRDF grant, we obtained evidence that cultured melanoma cells fall into two phenotypic classes. One of these is characterized by E-cadherin and MITF-M expression, and the other by N-cadherin and receptor tyrosine kinase Axl expression. We have hypothesized that these reflect alternative phenotypes that are adapted for proliferative and invasive modes of melanoma expansion.

Currently with Dr Maggie Kalev, Dr Marjan Askarian-Amiri, Dr Euphemia Leung and Professor Baguley, I am supervising doctoral research projects. The students are studying glutamate receptor expression and function in melanoma cells (Stacey D’mello), and long-noncoding RNA function in cancer cell lines (Debina Sarkar, Herah Hansji).

I am deeply involved with teaching from first to fourth year levels. This covers aspects of pathological process and of cancer cell genetics and biology. I am course director for MEDSCI 203 (Mechanisms of Disease; first semester), and of MEDSCI 101G (Environmental Threats to Human Health; second semester). The latter paper provides welcome variety in enabling me to zoom out from the microworld of cancer cells and their molecules, to a consideration of the interactions between the human environment and the human body.

Finally I have been an active protagonist for the public understanding of science. In particular, the ongoing disputations over evolutionary biology are of concern. It is a very small step from cancer genetics to evolutionary genetics. Mutations that reliably and non-controversially demonstrate monoclonality of tumours also reliably (and non-controversially) establish monophylicity of species. The new field of comparative genomics has provided unprecedentedly precise evidence for biological evolution. Theological considerations establish that a biblically-grounded theology and evolutionary science are not incompatible.

Recent relevant publications


Cancer and drug development

BRIDEWELL, D.J.A., PORTER, A.C.G., FINLAY, G.J. and BAGULEY, B.C. The role of topoisomerases and RNA transcription in the action of the antitumour benzonaphthyridine derivative SN 28049. Cancer Chemother and Pharmacol 62 (5):753-62, 2008.BAGULEY, B.C., FINLAY, G.J. ‘Stem cell niche versus cancer stem cell niche – differences and similarities.’ In: Stem Cell Biology in Health and Disease. Springer, Berlin. T. Dittmar, K.S. Zänker (Eds.), p.223-233, 2009.
DRUMMOND C.J., FINLAY, G.J., BROOME, L., MARSHALL, E.S., RICHARDSON, E., BAGULEY, B. C., ‘Action of SN 28049, a new DNA binding topoisomerase II-directed antitumour drug: comparison with doxorubicin and etoposide’. oposide’. Invest New Drugs 29, 1102-1110, 2011.
CHEN, Y.Y., FINLAY, G.J., KIRKER, J.A., MARSHALL E.S., RICHARDSON, E. and BAGULEY B.C. ‘In vivo and in vitro assessment of the action of SN 28049, a benzonaphthyridine derivative targeting topoisomerase II, on the murine Colon 38 carcinoma’. Invest New Drugs 29, 1504-10, 2011.
LEUNG, E, KIM, J.E., REWCASTLE, G.W., FINLAY, G.J., and BAGULEY, B.C. ‘Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells’. Cancer Biol Ther 11(11), 938-46, 2011.
CHARTERS, G.A., STONES, C. J., SHELLING, A. N., BAGULEY, B. C. and FINLAY, G. J. ‘Centrosomal dysregulation in human metastatic melanoma cell lines’. Cancer Genetics 204(9), 477-485, 2011.
KIM, J.E., STONES, C., JOSEPH, W.R., LEUNG, E., FINLAY, G.J., SHELLING, A.N., PHILLIPS, W.A., SHEPHERD, P.R. and BAGULEY, B.C., ‘Comparison of growth factor signalling pathway utilisation in cultured normal melanocytes and melanoma cell lines’. BMC Cancer 12,141, 2012.
STONES, C.J., KIM, J.E., JOSEPH, W.R., LEUNG, E., MARSHALL, S., FINLAY, G. J., SHELLING, A.N. and BAGULEY, B.C. ‘Comparison of responses of human melanoma cell lines to MEK and BRAF inhibitors.’ Frontiers in Genetics 4, article 66, 2013.
KIM, J.E., FINLAY, G.J. and BAGULEY B.C. ‘The role of the Hippo pathway in melanocytes and melanoma’. Frontiers in Oncology 3, article 123, 2013.
KIM, J.E., LEUNG, E., BAGULEY, B.C. and FINLAY, G.J. ‘Heterogeneity of expression of epithelial-mesenchymal transition (EMT) markers in melanocytes and melanoma cell lines’. Frontiers in Genetics 4, article 97, 2013.
LUKKA, P., CHEN, Y.Y., FINLAY, G., JOSEPH, W., RICHARDSON, E., PAXTON, J., and BAGULEY, B. ‘Tumour tissue selectivity in the uptake and retention of SN 28049, a new topoisomerase II-directed anticancer agent’. Cancer Chemotherapy and Pharmacology 72, 1013-22, 2013.
D'MELLO, S. A., FLANAGAN, J., GREEN, T., LEUNG, E., ASKARIAN-AMIRI, M.E., JOSEPH, W. R., MCCRYSTAL, M.R., ISAACS, R.J., SHAW, J.H.F., FURNEAUX, C. E., DURING, M.J., FINLAY, G. J., BAGULEY, B.C., KALEV-ZYLINSKA, M.L. ‘Evidence that GRIN2A mutations in melanoma correlate with decreased survival’. Frontiers in Oncology 3, article 333, 2014.

Science and religion

  1. FINLAY, G.J. 'Homo divinis: the ape that bears God's image'.  Science and Christian Belief 15, 17, 2003.
  2. FINLAY, G.J. 'Evolution as created history'. Science and Christian Belief 20, 67, 2008.
  3. FINLAY, G.J. 'Human evolution: how random process fulfils divine purpose'. Perspectives on Science and Christian Faith 60(2), 103, 2008.
  4. FINLAY, G.J, 'The evidence for evolution'. in Finlay, G. et al, Debating Darwin (Milton Keynes: Paternoster Press, 2009).
  5. FINLAY, G.J. 'The emergence of human distinctiveness: the genetic story'. in Jeeves, M. (ed), Rethinking Human Nature: A Multidisciplinary Approach (Grand Rapids and Cambridge: William B. Eerdmans, 2011).
  6. FINLAY G.J. Human Evolution: Genes, Genealogies and Phylogenies (Cambridge: CUP, 2013); publishers details may be seen at www.cambridge.org/9781107040120.  This book reviews the evidence for human evolution as it has arisen from the new field of comparative genomics.  There are four chapters, each of which discusses a different aspect of the genetic evidence.  It is written for people with some biological knowledge, but is intended for non-specialists - after all, the author is a cell biologist, and the power of the approach lies in the sheer simplicity of the genetic principles employed.  Mutations are used to track lineages of cells such as immune cells and cancer cells.  In the same way, mutations are used to track lineages of species.  A brief Prologue and Epilogue place the genetics in a wider framework.  They describe, for example, how faith in a Creator is fully compatible with evolutionary science and that conflict is entirely unnecessary.