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diagnosis treatment, lowering recurrence rates. Such combination therapies have even shown significant
curative benefits for hitherto refractory tumors. The implications from these findings are that repurposing
drugs such as NSAIDs like celecoxib or other agents that work in similar fashion should be highly
encouraged, as should their use in more clinical trials of metastatic disease and where biomarkers such as
constitutive NRF2-HIF protein expression are well defined.

DECLARATIONS
Acknowledgments
The authors thank Prof. R.K. Ralph for proofreading and editing of the manuscript.

Authors’ contributions
Design: Ralph SJ, Pritchard R
Literature research, data analysis: Ralph SJ, Nozuhur S, Moreno-Sánchez R, Rodríguez-Enríquez S, Pritchard R
Manuscript writing: Ralph SJ
Manuscript editing and revision: Ralph S J, Pritchard R, Moreno-Sánchez R, Enríquez SR

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was partially supported by CONACyT-Mexico grants No. 239930 and 281428 to RMS and 283144
to SRE. Rhys Pritchard was supported by an Australian postgraduate research award (APRA).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2018.

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