News and events from the Institute of Cancer Therapeutics

Harnessing the differences between cancer and non-cancer tissues presents new opportunities for selective targeting by anti-cancer drugs. CD13, a heavily glycosylated protein, is one example with significant unmet clinical potential in cancer drug discovery. Despite its high expression and activity in cancers, CD13 is also expressed in many normal tissues. Here, we report differential tissue glycosylation of CD13 across tissues and demonstrate for the first time that the nature and pattern of glycosylation of CD13 in preclinical cancer tissues are distinct compared to normal tissues. We identify cancer-specific O-glycosylation of CD13, which selectively blocks its detection in cancer models but not in normal tissues. In addition, the metabolism activity of cancer-expressed CD13 was observed to be critically dependent on its unique glycosylation. Thus, our data demonstrate the existence of discrete cancer-specific CD13 glycoforms and propose cancer-specific CD13 glycoforms as a clinically useful target for effective cancer-targeted therapy.

To read the full article

https://doi.org/10.1016/j.isci.2023.108219

Lead author, Dr. Francis M. Barnieh, a Research fellow at the ICT commented “This paper demonstrates for the first time the uniqueness of cancer-expressed CD13 compared to that expressed in normal tissues, which position CD13 as a potential target for cancer-targeted therapy. As an early career researcher, publishing my first independent and innovative research is critical for my career progression, and I am grateful to the UoB for the STARTER fellowship award”.

The Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer.

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Dr Helen Sheldrake (pictured above) lecturer in Organic and Medicinal Chemistry at the Institute of Cancer Therapeutics and first author on this article recently published in “Cancers” said ”I am very pleased to finally be able to publish the beginning of our cyclobutane integrin antagonist story after filing a patent on the most exciting compounds discovered. The cyclobutane structure is underused in medicinal chemistry; this paper highlights an easy method to make functionalised cyclobutanes and their potential in drug molecules".

Introduction: The seAFOod polyp prevention trial was a randomised, placebo controlled, 2 × 2 factorial trial of aspirin 300 mg and eicosapentaenoic acid (EPA) 2000 mg daily in individuals who had a screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Aspirin treatment was associated with a 20% reduction in colorectal polyp number at BCSP surveillance colonoscopy 12 months later. It is unclear what happens to colorectal polyp risk after short-term aspirin use.

Aim: To investigate colorectal polyp risk according to the original trial treatment allocation, up to 6 years after trial participation.

Methods: All seAFOod trial participants were scheduled for further BCSP surveillance and provided informed consent for the collection of colonoscopy outcomes. We linked BCSP colonoscopy data to trial outcomes data.

Results: In total, 507 individuals underwent one or more colonoscopies after trial participation. Individuals grouped by treatment allocation were well matched for clinical characteristics, follow-up duration and number of surveillance colonoscopies. The polyp detection rate (PDR; the number of individuals who had ≥1 colorectal polyp detected) after randomization to placebo aspirin was 71.1%. The PDR was 80.1% for individuals who had received aspirin (odds ratio [OR] 1.13 [95% confidence interval 1.02, 1.24]; p= 0.02). There was no difference in colorectal polyp outcomes between individuals who had been allocated to EPA compared with its placebo (OR for PDR 1.00 [0.91, 1.10]; p= 0.92).

Conclusion: Individuals who received aspirin in the seAFOod trial demonstrated increased colorectal polyp risk during post-trial surveillance. Rebound elevated neoplastic risk after short-term aspirin use has important implications for aspirin cessation driven by age-related bleeding risk.

To read the full article 

Prof. Paul Loadman from the Institute of Cancer Therapeutics (ICT) and co-author of the recently published article in Alimentary Pharmacology and Therapeutics said "This paper is the result of a long and fruitful collaboration with Prof Mark Hull (Consultant Gastroenterologist) in Leeds as part of the NIHR funded seAFOod trial looking at the influence of aspirin and an Omega -3 fatty acid (EPA) on patients with colorectal polyps. All analytical studies of complex fatty acid metabolism were undertaken at the ICT at the Univeristy of Bradford but other centres involved in the clinical side and importantly the statistical side included Newcastle, London, Sheffield and Oxford."

Delegates from across the region gathered in Bradford recently for the second annual ‘Bio-Partnering’ conference.

The event is hosted by the University of Bradford’s Institute for Cancer Therapeutics (ICT) and is designed to bring academia and industry together.

Professor Sherif El-Khamisy, Director of the ICT and Associate Dean for Research at the University of Bradford in the Faculty of Life Sciences, said: “The event was a huge success, with around 90 people from over 50 companies. Bradford has a strong reputation when it comes to conducting cancer research and showing how scientific research can have a tangible effect on society.

“We are delighted to have established Yorkshire Bio-Partnering at Bradford as an annual event that brings together academia and industry to highlight the challenges and successes of collaborative translational research and provide the opportunity to ignite new relationships”.

This year’s event featured keynote lectures from Prof Chris Twelves, nationally renowned medical oncologist from the University of Leeds, who discussed the UK Clinical Research Facility Network and how it supports collaborations between academia and the NHS in developing novel cancer therapeutics and Sophie Dale-Black from the UK Network (Midlands and North of England, British Business Bank) who discussed funding opportunities for business and collaborative research. 

Prof. El-Khamisy said: “With the Yorkshire region and the M62 corridor being home to many innovative companies in the healthcare and bioscience sector, the event celebrated specialist expertise and collaboration in pharmaceuticals, diagnostics, nutraceuticals and specialty ingredients.

To read the full article

The Institute of Cancer Therapeutics at the University of Bradford are currently advertising for 2 academic posts: (i) Cancer Biology/Therapeutics, (ii) Cancer Pharmacogenomics, and 2 research support roles: (i) Drug Metabolism and Molecular Biology, (ii) Medicinal chemistry.  Please see details below:

Job Opportunity at the University of Bradford: Lecturer in Cancer Biology and Therapeutics (Grade 8). Closing Date 2 May. https://jobs.bradford.ac.uk/HR0143909 

Job Opportunity at the University of Bradford: Assistant Professor in Cancer Pharmacogenomics (Grade 9). Closing Date 25 Apr. https://jobs.bradford.ac.uk/HR0144986 

Job Opportunity at the University of Bradford: Senior Technician in the Drug Metabolism & Pharmacokinetics  (DMPK) and Molecular Biology labs (Grade 7). Closing Date 2 May. https://jobs.bradford.ac.uk/HR0143808 

Job Opportunity at the University of Bradford: Medicinal Chemistry Technician (Grade 5). Closing Date 2 May 23. https://jobs.bradford.ac.uk/HR0143825  

The Institute of Cancer Therapeutics at the University of Bradford

Professor Sherif El-Khamisy Director of the Institute of Cancer Therapeutics presented a Keynote lecture at the BioNow Oncology & Precision Medicine Conference October 18/19th 2022 held at Alderley Park, Cheshire, UK. The conference was a a unique opportunity for researchers and industry to come together to explore the relationship between Oncology and Precision Medicine. The Conference included Keynote talks and panel discussions on topics ranging from clinical trials, to artificial intelligence, to the importance of hearing the cancer patient's voice. 

Prof El-Khamisy commented "At the Institute of Cancer Therapeutics, we focus on three main pillars; the basic discovery signs, making molecules and drugs for targets, target validation, and the preclinical development. What I talked about today is mainly the discovery signs. Particularly, how can we utilize our knowledge of how cells repair DNA damage and exploit this to treat cancer in a more targeted or precise way. In a study we published in Nature last week, we found high genomic damage in non-protein coding sequences, highlighting the need for doing whole genome sequencing rather than just focusing on the exon because a lot is happening outside the exons"

To read the full article covering the BioNow conference 

Prof. Sherif El-Khamisy Director of the Institute of Cancer Therapeutics