Using Glycan-Targeting Drugs to Block Prostate Cancer Bone Metastasis


IN PARTNERSHIP WITH PROSTATE CANCER RESEARCH (2021-PRESENT)

Jennifer Munkley, PhD, Newcastle University

Jennifer Munkley, PhD

There has been significant progress in treating prostate cancer over the last few decades, which has resulted in increased patient survival and improved quality of life. Despite these advances, there remains significant unmet need in a subset of patients, particularly those presenting with bone metastases. These can be debilitatingly painful and are invariably incurable. In order to better diagnose and treat these aggressive cancers, Jennifer Munkley is leading a team that will ask whether the complex sugars coating cells called glycans may hold the key to treating this recalcitrant stage of prostate cancer. Glycans are macromolecules which influence diverse aspects of normal and tumor cell physiology. The group has previously identified three types of glycans found in high levels in tumors and blood from men with metastatic prostate cancer. They developed a test called GlycoScore to detect changes to the glycan levels which they are studying as a means to diagnose aggressive prostate cancer. Now, they will examine the mechanisms behind how these glycans cause the tumors to metastasize, and examine whether they represent drug targets. By repurposing existing glycan-targeting drugs, they will ask if these could quickly be translated into the clinic for patients with no other treatment options. Targeting glycans represents a new and potentially transformative approach to prostate cancer diagnosis and treatment.

published research

Munkley J. Aberrant Sialylation in Cancer: Therapeutic Opportunities. Cancers (Basel). 2022.

Scott E, Hodgson K, Calle B, Turner H, Cheung K, Bermudez A, Marques FJG, Pye H, Yo EC, Islam K, Oo HZ, McClurg UL, Wilson L, Thomas H, Frame FM, Orozco-Moreno M, Bastian K, Arredondo HM, Roustan C, Gray MA, Kelly L, Tolson A, Mellor E, Hysenaj G, Goode EA, Garnham R, Duxfield A, Heavey S, Stopka-Farooqui U, Haider A, Freeman A, Singh S, Johnston EW, Punwani S, Knight B, McCullagh P, McGrath J, Crundwell M, Harries L, Bogdan D, Westaby D, Fowler G, Flohr P, Yuan W, Sharp A, de Bono J, Maitland NJ, Wisnovsky S, Bertozzi CR, Heer R, Guerrero RH, Daugaard M, Leivo J, Whitaker H, Pitteri S, Wang N, Elliott DJ, Schumann B, Munkley J. Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth. Oncogene. 2023.

Scott E, Archer Goode E, Garnham R, Hodgson K, Orozco-Moreno M, Turner H, Livermore K, Putri Nangkana K, Frame FM, Bermudez A, Jose Garcia Marques F, McClurg UL, Wilson L, Thomas H, Buskin A, Hepburn A, Duxfield A, Bastian K, Pye H, Arredondo HM, Hysenaj G, Heavey S, Stopka-Farooqui U, Haider A, Freeman A, Singh S, Johnston EW, Punwani S, Knight B, McCullagh P, McGrath J, Crundwell M, Harries L, Heer R, Maitland NJ, Whitaker H, Pitteri S, Troyer DA, Wang N, Elliott DJ, Drake RR, Munkley J. ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression. J Pathol. 2023.

Hodgson K, Orozco-Moreno M, Scott E, Garnham R, Livermore K, Thomas H, Zhou Y, He J, Bermudez A, Garcia Marques FJ, Bastian K, Hysenaj G, Archer Goode E, Heer R, Pitteri S, Wang N, Elliott DJ, Munkley J. The role of GCNT1 mediated O-glycosylation in aggressive prostate cancer. Sci Rep. 2023.

Orozco-Moreno M, Visser EA, Hodgson K, Hipgrave Ederveen AL, Bastian K, Goode EA, Öztürk Ö, Pijnenborg JFA, Eerden N, Moons SJ, Rossing E, Wang N, Haan N, Büll C, Boltje TJ, Munkley J. Targeting aberrant sialylation and fucosylation in prostate cancer cells using potent metabolic inhibitors. Glycobiology. 2023.

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