Personalized Network-Based Treatments in Oncology

Robin, Xavier; Creixell, Pau; Radetskaya, O; Santini, Cristina Costa; Longden, James; Linding, Rune

doi:10.1038/clpt.2013.171

Cited by 24 publications

(16 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Signaling networks in which protein kinases operate are highly complex, but we believe that understanding the regulatory functions of kinases may be a valid means to identify more effective therapies against cancer (146,147). Many drug kinase inhibitors are already on the market (122,133–137) but, often, their effectiveness is reduced due to the development of complex mechanisms of drug resistance (149).…”

Section: Discussionmentioning

confidence: 99%

The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

Ardito

Giuliani

Perrone

et al. 2017

International Journal of Molecular Medicine

934

689

View full text Add to dashboard Cite

Protein phosphorylation is an important cellular regulatory mechanism as many enzymes and receptors are activated/deactivated by phosphorylation and dephosphorylation events, by means of kinases and phosphatases. In particular, the protein kinases are responsible for cellular transduction signaling and their hyperactivity, malfunction or overexpression can be found in several diseases, mostly tumors. Therefore, it is evident that the use of kinase inhibitors can be valuable for the treatment of cancer. In this review, we discuss the mechanism of action of phosphorylation, with particular attention to the importance of phosphorylation under physiological and pathological conditions. We also discuss the possibility of using kinase inhibitors in the treatment of tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

Ardito

Giuliani

Perrone

et al. 2017

International Journal of Molecular Medicine

934

689

View full text Add to dashboard Cite

show abstract

“…a molecular interaction network [10]. Although this network has spatial and dynamic dimensions which at present remain largely unexplored due to technological or logistical limitations, there is already a growing number of examples where network-based analysis strategies have been instrumental [11,12,13]. For instance, a deeper understanding of why sustained treatment with EGFR inhibitors can lead to dramatic sensitization of cancer cell lines to cytotoxic agents was possible thanks to a systems approach [13].…”

Section: Introductionmentioning

confidence: 99%

Signalling entropy: A novel network-theoretical framework for systems analysis and interpretation of functional omic data

Teschendorff

Sollich

Kühn

2014

Methods

View full text Add to dashboard Cite

A key challenge in systems biology is the elucidation of the underlying principles, or fundamental laws, which determine the cellular phenotype. Understanding how these fundamental principles are altered in diseases like cancer is important for translating basic scientific knowledge into clinical advances. While significant progress is being made, with the identification of novel drug targets and treatments by means of systems biological methods, our fundamental systems level understanding of why certain treatments succeed and others fail is still lacking. We here advocate a novel methodological framework for systems analysis and interpretation of molecular omic data, which is based on statistical mechanical principles. Specifically, we propose the notion of cellular signalling entropy (or uncertainty), as a novel means of analysing and interpreting omic data, and more fundamentally, as a means of elucidating systems-level principles underlying basic biology and disease. We describe the power of signalling entropy to discriminate cells according to differentiation potential and cancer status. We further argue the case for an empirical cellular entropy-robustness correlation theorem and demonstrate its existence in cancer cell line drug sensitivity data. Specifically, we find that high signalling entropy correlates with drug resistance and further describe how entropy could be used to identify the achilles heels of cancer cells. In summary, signalling entropy is a deep and powerful concept, based on rigorous statistical mechanical principles, which, with improved data quality and coverage, will allow a much deeper understanding of the systems biological principles underlying normal and disease physiology.

show abstract

“…One challenge to implementing network medicine is the limited number of drug targets accessible with FDA approved drugs, and the promiscuity of many of these drugs [125]. The use of multiple small molecule drugs at low doses is one possible solution [125, 126], but in the long run engineered proteins introduced into the diseased cells to reprogram aberrant cell signaling networks holds the greatest promise for specific control [120].…”

Section: Smart Response Drug System Designmentioning

confidence: 99%

“…The use of multiple small molecule drugs at low doses is one possible solution [125, 126], but in the long run engineered proteins introduced into the diseased cells to reprogram aberrant cell signaling networks holds the greatest promise for specific control [120]. The use of engineered proteins to reprogram cell signaling networks is in fact a biomimetic approach, which can leverage increasing scientific knowledge of similar methods used by pathogens to disrupt and usurp signaling pathways [127, 128].…”

Section: Smart Response Drug System Designmentioning

confidence: 99%

Protein Engineering: A New Frontier for Biological Therapeutics

Tobin¹,

Richards²,

Callender³

et al. 2015

CDM

View full text Add to dashboard Cite

Protein engineering holds the potential to transform the metabolic drug landscape through the development of smart, stimulus-responsive drug systems. Protein therapeutics are a rapidly expanding segment of Food and Drug Administration approved drugs that will improve clinical outcomes over the long run. Engineering of protein therapeutics is still in its infancy, but recent general advances in protein engineering capabilities are being leveraged to yield improved control over both pharmacokinetics and pharmacodynamics. Stimulus-responsive protein therapeutics are drugs which have been designed to be metabolized under targeted conditions. Protein engineering is being utilized to develop tailored smart therapeutics with biochemical logic. This review focuses on applications of targeted drug neutralization, stimulus-responsive engineered protein prodrugs, and emerging multicomponent smart drug systems (e.g., antibody-drug conjugates, responsive engineered zymogens, prospective biochemical logic smart drug systems, drug buffers, and network medicine applications).

show abstract

Personalized Network-Based Treatments in Oncology

Cited by 24 publications

References 50 publications

The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

Signalling entropy: A novel network-theoretical framework for systems analysis and interpretation of functional omic data

Protein Engineering: A New Frontier for Biological Therapeutics

Contact Info

Product

Resources

About