title: Dynamic versus static biomarkers in cancer immune checkpoint blockade: unravelling complexity.
abstract: Recently, there has been a coordinated effort from academic institutions and the pharmaceutical industry to identify biomarkers that can predict responses to immune checkpoint blockade in cancer. Several biomarkers have been identified; however, none has reliably predicted response in a sufficiently rigorous manner for routine use. Here, we argue that the therapeutic response to immune checkpoint blockade is a critical state transition of a complex system. Such systems are highly sensitive to initial conditions, and critical transitions are notoriously difficult to predict far in advance. Nevertheless, warning signals can be detected closer to the tipping point. Advances in mathematics and network biology are starting to make it possible to identify such warning signals. We propose that these dynamic biomarkers could prove to be useful in distinguishing responding from non-responding patients, as well as facilitate the identification of new therapeutic targets for combination therapy.
authors.affiliation: School of Medicine and Pharmacology and National Centre for Asbestos Related Diseases, University of Western Australia, 5th Floor QQ Block, 6 Verdun Street, Nedlands, Perth, Western Australia 6009, Australia.
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Lesterhuis
authors.affiliation: Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, Western Australia 6872, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bosco
authors.affiliation: School of Medicine and Pharmacology and National Centre for Asbestos Related Diseases, University of Western Australia, 5th Floor QQ Block, 6 Verdun Street, Nedlands, Perth, Western Australia 6009, Australia.|Department of Medical Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Avenue 6009, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Millward
authors.affiliation: School of Mathematics and Statistics, University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia.|CSIRO, Mineral Resources, 26 Dick Perry Avenue, Kensington, Western Australia 6152, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Small
authors.affiliation: School of Medicine and Pharmacology and National Centre for Asbestos Related Diseases, University of Western Australia, 5th Floor QQ Block, 6 Verdun Street, Nedlands, Perth, Western Australia 6009, Australia.|Department of Medical Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Avenue 6009, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
authors.affiliation: School of Medicine and Pharmacology and National Centre for Asbestos Related Diseases, University of Western Australia, 5th Floor QQ Block, 6 Verdun Street, Nedlands, Perth, Western Australia 6009, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lake
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D017711:Nonlinear Dynamics
chemical_list: D014408:Biomarkers, Tumor