Targeting GALNT7 and truncated O-glycans for improved treatment of prostate cancer
Lead Research Organisation:
Newcastle University
Department Name: Biosciences Institute
Abstract
Prostate cancer is the most common cancer in men in the UK. For stage 4 prostate cancer where cancer cells have metastasised to nearby lymph nodes or to other parts of the body like bones and liver, the five-year survival rate drops to around 50% with no available cure. Standard treatments for advanced prostate cancer include androgen deprivation therapy (ADT), androgen signalling inhibition (ARSI) and chemotherapy. However, a large number of patients stop responding to treatments and develop metastatic castration-resistant prostate cancer. These challenges highlight the need for developing novel therapeutic approaches to improve the current treatments for advanced prostate cancer.
Glycans are carbohydrates that are present on all eukaryotic cell surfaces. Aberrant glycosylation is identified as a hallmark of cancer and can be linked to all aspects of cancer progression. Previous work in the Munkley group identified that GALNT7, which encodes the glycosyltransferase enzyme GalNAc transferase 7, is upregulated in prostate cancer. GALNT7 was shown to modify the O-glycosylation of prostate cancer cells and promote the synthesis of the Tn antigen, a cancer associated truncated O-glycan. GALNT7 was also found to promote tumour growth in vivo and suppress immune signalling pathways. To build on this work, this study will explore the role of GALNT7 and truncated O-glycans in the context of prostate cancer metastasis and investigate whether GALNT7 and/or truncated O-glycans can be targeted therapeutically.
This project aims to discover the role of GALNT7 and truncated O-glycans in prostate cancer progression and obtain proof-of principle data to show that targeting GALNT7 and/or its glycans holds therapeutic potential for prostate cancer.
Objectives
1. Decipher the prostate tumour glyco-code using immunohistochemistry and identify new diagnostic and prognostic biomarkers and glycans which hold promise to be targeted therapeutically.
2. Gain a clear understanding of the role of GALNT7 and truncated O-glycans in prostate cancer progression (in the context of metastasis, the tumour microenvironment and the immune system).
3. Target GALNT7 and/or truncated O-glycans to develop new therapies for prostate cancer.
Glycans are carbohydrates that are present on all eukaryotic cell surfaces. Aberrant glycosylation is identified as a hallmark of cancer and can be linked to all aspects of cancer progression. Previous work in the Munkley group identified that GALNT7, which encodes the glycosyltransferase enzyme GalNAc transferase 7, is upregulated in prostate cancer. GALNT7 was shown to modify the O-glycosylation of prostate cancer cells and promote the synthesis of the Tn antigen, a cancer associated truncated O-glycan. GALNT7 was also found to promote tumour growth in vivo and suppress immune signalling pathways. To build on this work, this study will explore the role of GALNT7 and truncated O-glycans in the context of prostate cancer metastasis and investigate whether GALNT7 and/or truncated O-glycans can be targeted therapeutically.
This project aims to discover the role of GALNT7 and truncated O-glycans in prostate cancer progression and obtain proof-of principle data to show that targeting GALNT7 and/or its glycans holds therapeutic potential for prostate cancer.
Objectives
1. Decipher the prostate tumour glyco-code using immunohistochemistry and identify new diagnostic and prognostic biomarkers and glycans which hold promise to be targeted therapeutically.
2. Gain a clear understanding of the role of GALNT7 and truncated O-glycans in prostate cancer progression (in the context of metastasis, the tumour microenvironment and the immune system).
3. Target GALNT7 and/or truncated O-glycans to develop new therapies for prostate cancer.
Organisations
People |
ORCID iD |
| Jennifer Munkley (Primary Supervisor) | |
| Jessica Peng (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/W006944/1 | 01/10/2022 | 30/09/2028 | |||
| 2884922 | Studentship | MR/W006944/1 | 01/10/2023 | 30/09/2027 | Jessica Peng |