A role for deferasirox as an anti-neoplastic and chemosensitising agent in gastrointestinal cancer

Bedford, Matthew Robert (2015). A role for deferasirox as an anti-neoplastic and chemosensitising agent in gastrointestinal cancer. University of Birmingham. Ph.D.

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Abstract

Cancer of the gastrointestinal tract remains a significant cause of morbidity and mortality. Although surgical resection of the primary tumour remains the cornerstone of curative treatment, chemotherapy forms an increasingly important component of the management armamentarium. Response to therapy, however, is by no means uniform and thus the development of new agents is highly desirable.

There is a significant body of evidence implicating iron in the malignant progression of gastrointestinal cancer. Tumours acquire an excess of iron which in turn propagates their malignant phenotype. This project aimed to demonstrate that a strategy to deplete tumour cells of iron using the licensed iron chelator Deferasirox was effective in the treatment of oesophageal and colorectal cancer.

Deferasirox significantly impedes cellular viability and proliferation both \(in-vitro\) and \(in-vivo\) in oesophageal and colorectal cancer models. The drug can overcome established chemotherapy resistance and may also act as a chemosensitiser. The disturbance of normal intracellular iron homeostasis and increased dependence of gastrointestinal tumour cells on iron means chelation may offer targeted therapy. Certain iron regulatory proteins may also serve as biomarkers for treatment efficacy. Deferasirox therefore represents an effective and well tolerated adjunct to existing therapies that should be considered for future clinical trials.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):