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Biological significance, predictive value and targeting of cell surface antigens in colorectal cancer.


   Faculty of Science, Engineering and Computing

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Despite major advances in its early detection, preventive measures and therapeutic options, colorectal cancer is the fourth most commonly diagnosed cancer and the third leading cause of cancer deaths worldwide. In order to reduce deaths due to colorectal cancer, it is essential to discover additional biomarkers of diagnostic, prognostic and therapeutic values in such patients. In the past few years, we have been investigating the role of human epidermal growth factor receptor (EGFR) family members in the progression of colorectal cancer, their prognostic significance and predictive value for the response to therapeutics (1-2). More recently, we developed several in house monoclonal antibodies (mAbs) against antigens with high level of expression on the cell surface of human pancreatic cancer cells and other cancer cells (3).

The aims of this three-year full-time PhD project are to investigate the relative expression and prognostic significance of such antigens in patients with colorectal cancer. We shall also investigate the relative expression of such antigens on the cell surface of human colorectal cancer cells and the therapeutic potential of such mAbs when used alone and in combination with the small molecule tyrosine kinase inhibitor (TKIs) or cytotoxic drugs on the growth and migration of human colorectal cancer cell lines and their drug-resistant variants. The results of this investigation should not only help to define the role of such antigens in the malignant behaviour of colorectal cancer but also the therapeutic advantages of mAbs targeting such antigens when used in combinations with other drugs.


Funding Notes

No funding is available for this project

References

1. Khelwatty SA, Essapen S, Bagwan I, Green M, Seddon AM, Modjtahedi H. Co-expression and prognostic significance of putative CSC markers CD44, CD133, wild-type EGFR and EGFRvIII in metastatic colorectal cancer (2019). Oncotarget. 0(18): 1704–1715.

2. Khelwatty S, Essapen S, Seddon AM, Fan Z and Modjtahedi H (2015) Acquired resistance to anti-EGFR mAb ICR62 in cancer cells is accompanied by an increased EGFR expression, HER-2/HER-3 signalling and sensitivity to pan HER blockers. British Journal of Cancer, Sep 29;113(7):1010-9. ISSN (print) 0007-0920

3. Pinilla GA, Dalgleish AG, Mudan S, Bagwan I, Walker AJ, Modjtahedi H (2020). Development and application of two novel monoclonal antibodies against overexpressed CD26 and integrin α3 in human pancreatic cancer. Scientific Reports 10: 537.


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