Exploiting Synthetic Lethality and Network Biology to Overcome EGFR Inhibitor Resistance in Lung Cancer.
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Embargo End Date
ICR Authors
Authors
Vyse, S
Howitt, A
Huang, PH
Howitt, A
Huang, PH
Document Type
Journal Article
Date
2017-06-16
Date Accepted
2017-04-27
Abstract
Despite the recent approval of third-generation therapies, overcoming resistance to epidermal growth factor receptor (EGFR) inhibitors remains a major challenge in non-small cell lung cancer. Conceptually, synthetic lethality holds the promise of identifying non-intuitive targets for tackling both acquired and intrinsic resistance in this setting. However, translating these laboratory findings into effective clinical strategies continues to be elusive. Here, we provide an overview of the synthetic lethal approaches that have been employed to study EGFR inhibitor resistance and review the oncogene and non-oncogene signalling mechanisms that have thus far been unveiled by synthetic lethality screens. We highlight the potential challenges associated with progressing these discoveries into the clinic including context dependency, signalling plasticity, and tumour heterogeneity, and we offer a perspective on emerging network biology and computational solutions to exploit these phenomena for cancer therapy and biomarker discovery. We conclude by presenting a number of tangible steps to bolster our understanding of fundamental synthetic lethality mechanisms and advance these findings beyond the confines of the laboratory.
Citation
Journal of molecular biology, 2017, 429 (12), pp. 1767 - 1786
Source Title
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
ISSN
0022-2836
eISSN
1089-8638
Collections
Research Team
Protein Networks
Molecular and Systems Oncology
Molecular and Systems Oncology