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Role of Wnt pathway dysregulation in Multiple Myeloma (MM)

thesis
posted on 2017-04-12, 02:28 authored by Ioanna Savvidou
MM is a highly heterogeneous and incurable disease. Available evidence suggests that the Wnt/canonical pathway contributes to both disease progression and drug resistance confirming the pathway as an attractive potential therapeutic target. Wnt/β-catenin up-regulation can be the result of multiple factors, which in solid tumour can co-exist, all further enhancing pathway activity. Moreover, we identified a possible additional mechanism relating to the receptor complex expression. Among a variety of Wnt/canonical pathway inhibitors that we tested, BC2059 was shown to have the best anti-MM results in clinically feasible doses, with a favourable in vivo toxicity profile. In the era of combinational chemotherapy BC2059 also proved to exert significant synergistic anti-MM effect both in combination with well-established and novel anti-MM drugs, warranting further investigation. Finally, exploring in more detail the cytotoxic and pro-survival effect of BC2059 we were able to identify that inhibition of autophagy was able to amplify its anti-MM effect. This approach may represent a new paradigm for enhancing the activity of established or novel anti-MM regimens.

History

Principal supervisor

Andrew Spencer

Additional supervisor 1

Tiffany Khong

Year of Award

2017

Department, School or Centre

Australian Centre for Blood Diseases

Additional Institution or Organisation

Clinical Haematology

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Medicine Nursing and Health Sciences

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    Faculty of Medicine, Nursing and Health Sciences Theses

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