Professor Robert Falconer,

Professor of Medicinal Chemistry

Research

The Falconer group is primarily focused on the tumour glycocalyx as a therapeutictarget, and glycosyltransferases in particular, and in tumourprotease-activated drug delivery. He is an experienced principal investigatorand has secured funding from research councils and medical charities. Hecurrently holds grants from Breast Cancer Now, Bone Cancer Research Trust, and Incanthera plc. He also leads the newlycreated Institute of Cancer Therapeutics Doctoral Training Centre (ICT DTC), establishedin 2019 following a major 10-year investment by Incanthera plc (£2m).

He has a keen interest and track record in knowledge transfer and cancer drugdevelopment. As lead medicinal chemist, he is co-founder and technologyco-inventor of the ‘crocus smart-bomb’ (MMP-targeted anti-vascular agentICT2588), which is being progressed to the clinic by Ellipses Pharma/IncantheraLtd. Incanthera is an ICT/University of Bradford spin-out company (www.incanthera.com).He is co-inventor on four patents associated with this technology.

Current ResearchProjects

1. Anti-canceragents targeting the tumour glycocalyx

This research is focused on the design, synthesisand biological evaluation of inhibitors of polysialyltransferase (and prodrugs thereof) as a means bywhich to modulate tumour cell migration, invasion and metastasis. The polysialyltransferasesare responsible for the tumour cell surface biosynthesis of polysialic acid(polySia), which plays a key role in the metastatic process in a number ofcancers (see review: Curr. Cancer Drug Targets, 2012, 12,925-939). We are employing computational methods to aid the inhibitor designprocess and have the capability to assess enzyme inhibition (see Carbohydrate Polymers, 2021, 259, 117741 and Analyst, 2020, 145.4512-4521, ), cell-surfacepolySia decoration (see review: Carbohydrate Polymers, 2019, 224, 11545), and effects on cell-cell and cell-matrix adhesion, cellmigration and invasion (see PLoS ONE, 2013, 8, e73366; Scientific Reports, 2016, 6, 33026; ChemBioChem, 2017,18, 1332-1337). This work is currently supported by a PhD studentship in the ICT Doctoral Training Centre.

2.Endoprotease-activated therapeutics

This research is focused on the transformation ofpotent cytotoxic agents to inactive peptide-conjugates that are selectivelyactivated within the tumour microenvironment. We are currently interested inthe matrix metalloproteinases (MMPs) which are a family of endopeptidases, and other endoporteases overexpressed in tumours. We are employing both solution and solid phasechemistry to synthesise peptide-based therapeutics with potent but selective cytotoxicityin vivo. Compounds areassessed for in vitro cytotoxicity, successful cleavage in tumourtissue, stability in normal tissues (liver, kidney, lung) and plasma (key collaboration Prof Paul Loadman, Dr Huw Jones, ICT), beforebeing evaluated in vivo (key collaboration with Dr Steve Shnyder, ICT). We are additionally pursuing prodrugs of DNA repair targets in collaboration with Prof Sherif El-Khamisy (ICT & University of Sheffield). Our lead compound ICT2588 was commercialised through Incanthera plc (see Cancer Research, 2010, 70, 6902-6912; Molecular Pharmaceutics, 2014, 11, 1294−1300).

We have a particular interest in osteosarcoma, and in developing kinder treatments for this deadly disease that mainly affects children and young adults. Funded by the Bone Cancer Research Trust (BCRT) through a PhD studentship (2018-22), and a project grant (2023-26), our aim is to achieve preclinical proof-of-concept for an MMP-activated tumour-targeted prodrug of methotrexate. We will evaluate our lead molecules in clinically-relevant orthotopic models of the disease in collaboration with Prof Allie Gartland (University of Sheffield).

A new project focused on neuroblastoma, and targeted delivery of an inhibitor of DNA repair, funded by Worldwide Cancer Research (2023-25) commenced in April 2023.

We continue our long-standing collaboratiion with the Daldrup-Linkgroup (Standford University, USA) to further develop a novel theranostics, which have shown efficacy in breast cancer (see Small, 2014, 10, 566-575) and glioblastoma (see Molecular Cancer Therapeutics, 2017,16, 1909-1921 and Nanotheranostics, 2019, 3, 299-310).

Current projects are additionally focused on development oftreatments for breast cancer, prostate cancer and neuroblastoma. Our research iscurrently funded by Breast Cancer Now, Bone Cancer Research Trust, Worldwide Cancer Research, the ICT Doctoral Training Centre, and the Masonic Charitable Foundation.

Current Team members

PhD students

Gabriel Nwokolo (Masonic Charitable Foundation 2024-28)

Zubeda Khatoon (ICT DTC 2022-26)

Louise Stevenson (DiMeN/University of Sheffield with Prof Sherif El-Khamisy 2021-24)

Post-Doctoral Researchers

Dr Goreti Ribeiro Morais (ICT DTC)

Dr Hannah Spencer (BCRT 2023-26)

Dr April Baral (Worldwide Cancer Research 2023-25)

Research projects

Research supervision

Professor Robert Falconer is responsible for the supervision of 3 postgraduate researchers at the University of Bradford.