Interview with Professor Mohamed El-Tanani from the University of Bradford

The cover for issue 79 of Oncotarget features Figure 8, "Summary figure of proposed pimozide mechanisms," by Dakir, et al.

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A commonly-used anti-psychotic drug could also be effective against triple negative breast cancer, the form of the disease that is most difficult to treat, new research has found. The study, led by the University of Bradford, also showed that the drug, Pimozide , has the potential to treat the most common type of lung cancer.

Anti-psychotic drugs are known to have anti-cancer properties, with some, albeit inconclusive, studies showing a reduced incidence of cancer amongst people with schizophrenia . The new research, published in Oncotarget, is the first to identify how one of these drugs acts against triple negative breast cancer, with the potential to be the first targeted treatment for the disease.

Lead researcher, Professor Mohamed El-Tanani from the University of Bradford , said: "Triple negative breast cancer has lower survival rates and increased risk of recurrence. It is the only type of breast cancer for which only limited targeted treatments are available. Our research has shown that Pimozide could potentially fill this gap. And because this drug is already in clinical use, it could move quickly into clinical trials. "

The researchers, from the University of Bradford, Queen 's University Belfast and the University of Salamanca , tested Pimozide in the laboratory on triple negative breast cancer cells, non-small cell lung cancer cells and normal breast cells. They found that at the highest dosage used, up to 90% of the cancer cells died following treatment with the drug, compared with only 5% of the normal cells.

They then tested the drug on mice implanted with triple negative breast cancer. Tumours in mice treated with Pimozide were 65% smaller than in untreated mice and the number of tumours reduced by up to 61%. The drug also helped to prevent the cancer spreading: treated mice had up to 94% fewer metastases in the lung than mice who didn 't receive Pimozide.

The drug involved in the research wasn 't chosen at random. Previous research by Professor El-Tanani has shown that a certain protein, called Ran-GTP, plays a significant role in enabling the growth and spread of a number of cancers, including triple negative breast cancer.

When Professor El-Tanani mapped thousands of existing drugs against this protein, to identify which would be most effective in blocking Ran-GTP, Pimozide came top of the table. He then worked with colleagues to test the drug in cells and mice and identify the mechanisms by which the drug, and the inhibition of Ran-GTP, were affecting the cancer.

The study found that, in addition to reducing proliferation of triple negative breast cancer cells and increasing the percentage of cells that died, the drug was able to reduce migration and invasion of these cancer cells. It suppressed production of a protein, called VEGFR2, that supports blood supply to tumours, prevented production of an enzyme that is linked to metastasis and prevented the production of cells called myofibroblasts that help promote tumour growth.

"There are many molecular pathways that are hyperactive in cancer, " explained Professor El-Tanani. "Our study shows that by acting as a Ran-GTP inhibitor, Pimozide was able to block a number of key pathways that contribute to triple negative breast cancer growing and spreading. "

Now the team have proven the effectiveness of this drug in vitro and in vivo , a patent has been applied for and they are actively seeking funding to move to clinical trials, to test its impact in humans.

For more information, contact:

Mark Thompson, Media Relations Manager, University of Bradford: tel +44 (0)1274 236510, mob +44 (0) 7500 762165, email [email protected]

Abigail Chard, Campus PR: tel: 0+44 (0)113 258 9880, mob +44 (0)7960 448532, email [email protected]

Notes to editors: 'The Anti-Psychotic Drug Pimozide is a Novel Chemotherapeutic for Breast Cancer 'by EL-Habib Dakir, Adam Pickard, Kirtiman Srivastava, Cian M. McCrudden, Stephane R Gross, Stephan Llyod, Shu-Dong Zhang, Andriana Margariti, Richard Morgan, Philip S. Rudland and Mohamed El-Tanani is published in Oncotarget

A photo of Professor El-Tanani is available.
A patent application for this use of Pimozide has been filed —publication number WO2018065771A1.

The research involved:

  • Institute of Cancer Therapeutics, University of Bradford
  • Centre for Cancer Research and Cell Biology, Queen 's University Belfast
  • School of Pharmacy, Queen 's University Belfast
  • Centre of Experimental Medicine, Queen 's University Belfast
  • Instituto de Biolog Ía Molecular y Celular del C áncer, Universidad de Salamanca
  • Centro de Investigaci ón Biom édicas en Red de C áncer (CIBERONC), Universidad de Salamanca
  • School of Life and Health Sciences, Aston University
  • Northern Ireland Centre for Stratified Medicine, University of Ulster
  • Institute of integrative Biology, University of Liverpool, Liverpool, UK

About the University of Bradford

Founded in 1966, the University of Bradford is one of the UK 's traditional universities. It is a research-intensive institution, ranked in the top 50 in the UK for the quality of its research, with three quarters being classed as either world-leading or internationally excellent in the 2014 Research Excellence Framework (REF). The University was ranked No 1 in Yorkshire for employed graduates obtaining professional &managerial level jobs.
Known for its strong emphasis on employability skills and knowledge transfer work with businesses, the University has a truly global make up with over 20 % of its student population being international. The University is also a leader in sustainable development and education, and is 8th greenest in the world according to UI GreenMetric World University Rankings 2015.

Full text - https://doi.org/10.18632/oncotarget.26175

Correspondence to - EL-Habib Dakir - [email protected] and Mohamed El-Tanani - [email protected]

Keywords - pimozide , breast cancer , DSB , apoptosis , xenograft

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