Talk Title: Identification of effective combinatorial therapies for cancer using integrated pathway modelling

Abstract

The advent of targeted drugs has revolutionised cancer treatment in the 21st century. Yet, the increasing emergence of resistance to anticancer treatments as single-drug therapies have posed significant challenges in the clinic, and constitutes a major hurdle towards a cure for many cancer types. As a result, combination therapies where two or more agents are combined in a treatment have emerged recently as an effective strategy to overcome drug resistance, and are being actively investigated in many cancers. These efforts are however primarily based on empirical observations and large, expensive experimental screens. There is a strong lack of unbiased approaches to predict effective drug combinations, and more importantly, to prioritise them and stratify patients for optimal benefit. In this lecture, I will demonstrate how kinetic and dynamic pathway modelling could be used in conjunction with experimentation as a novel and effective approach to fulfil these goals. I will focus on targeting a multi-pathway Receptor Tyrosine Kinase signalling network in triple-negative breast cancer (TNBC), a highly aggressive breast cancer subtype with no targeted treatment available, as an illustrative example. I will show how integrated modelling-experiments could help rationally identify the best combinatorial drugs and discuss methods to do this in a personalised manner, thereby stratifying patients into subgroups with different degrees of predicted treatment response. Given its adaptability and scalability, this approach could be applied to other signalling systems and/or tumour types and so has the potential to push the frontier of cancer treatment development.

Lan Nguyen

Biography

Dr Lan Nguyen, Head of the Network Modelling Laboratory, Biomedicine Discovery Institute (BDI) and the Department of Biochemistry & Molecular Biology, Faculty of Medicine, Health and Nursing, Monash University.

Dr Lan Nguyen is currently the Head of the Network Modelling Laboratory at the Biomedicine Discovery Institute (BDI) and the Department of Biochemistry & Molecular Biology, Faculty of Medicine, Health and Nursing, Monash University. He studied Applied Maths & Computer Science before completing a PhD in Computational Systems Biology in Christchurch, New Zealand in early 2010. During this time he received mixed training in mathematical modelling and cell biology. He then undertook postdoctoral training under mentorship of systems biology pioneer Prof Boris Kholodenko at Systems Biology Ireland (SBI), a leading institute dedicated to systems biology research in Europe. He became a junior group leader at SBI in 2014 before reallocating to Monash late 2015 to establish his independent research laboratory.

His research interest revolves around network biology and the integration of computational and experimental methods to obtain deep, systems-level understanding of biological networks, as well as to advance treatments for cancer. As such, his lab consists of both dry and wet-lab aspects and personnel.

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