Professor Robert Falconer,

Professor of Medicinal Chemistry

Research

The Falconer group is primarily focused on the tumour glycocalyx as a therapeutic target, and glycosyltransferases in particular, and in tumour protease-activated drug delivery. He is an experienced principal investigator and has secured funding from research councils and medical charities. He currently holds grants from Breast Cancer Now, Bone Cancer Research Trust, and Incanthera plc. He also leads the newly created Institute of Cancer Therapeutics Doctoral Training Centre (ICT DTC), established in 2019 following a major 10-year investment by Incanthera plc (£2m). He has a keen interest and track record in knowledge transfer and cancer drug development. As lead medicinal chemist, he is co-founder and technology co-inventor of the ‘crocus smart-bomb’ (MMP-targeted anti-vascular agent ICT2588), which is being progressed to the clinic by Ellipses Pharma/Incanthera Ltd. 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 Research Projects 1. Anti-cancer agents targeting the tumour glycocalyx This research is focused on the design, synthesis and biological evaluation of inhibitors of polysialyltransferase (and prodrugs thereof) as a means by which to modulate tumour cell migration, invasion and metastasis. The polysialyltransferases are responsible for the tumour cell surface biosynthesis of polysialic acid (polySia), which plays a key role in the metastatic process in a number of cancers (see review: Curr. Cancer Drug Targets, 2012, 12, 925-939). We are employing computational methods to aid the inhibitor design process and have the capability to assess enzyme inhibition (see Carbohydrate Polymers, 2021, 259, 117741 and Analyst, 2020, 145. 4512-4521, ), cell-surface polySia decoration (see review: Carbohydrate Polymers, 2019, 224, 11545), and effects on cell-cell and cell-matrix adhesion, cell migration 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 therapeuticsThis research is focused on the transformation of potent cytotoxic agents to inactive peptide-conjugates that are selectively activated within the tumour microenvironment. We are currently interested in the matrix metalloproteinases (MMPs) which are a family of endopeptidases, and other endoporteases overexpressed in tumours. We are employing both solution and solid phase chemistry to synthesise peptide-based therapeutics with potent but selective cytotoxicity in vivo. Compounds are assessed for in vitro cytotoxicity, successful cleavage in tumour tissue, stability in normal tissues (liver, kidney, lung) and plasma (key collaboration Prof Paul Loadman, Dr Huw Jones, ICT), before being 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-Link group (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 of treatments for breast cancer, prostate cancer and neuroblastoma. Our research is currently funded by Breast Cancer Now, Bone Cancer Research Trust, Worldwide Cancer Research, the ICT Doctoral Training Centre, and the Masonic Charitable Foundation.Current Team membersPhD studentsGabriel 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 supervision

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