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Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry–Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors

1
Department of Pediatric Surgery, University Children’s Hospital Basel, 4031 Basel, Switzerland
2
Department Neurofarba, Sezione di Scienze farmaceutiche, University of Florence, 50139 Florence, Italy
3
Biological Calorimetry Lab, Department of Biomedical Engineering, University of Basel, 4123 Allschwil, Basel, Switzerland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 4984; https://doi.org/10.3390/ijms20204984
Received: 22 August 2019 / Revised: 3 October 2019 / Accepted: 5 October 2019 / Published: 9 October 2019
(This article belongs to the Special Issue Protease and Carbonic Anhydrase Inhibitors, II)
We present a novel approach to a personalized therapeutic concept for solid tumors. We illustrate this on a rare childhood tumor for which only a generalized treatment concept exists using carbonic anhydrase IX and aquaporin 1 inhibitors. The use of microcalorimetry as a refined in vitro method for evaluation of drug susceptibility in organotypic slice culture has not previously been established. Rapid microcalorimetric drug response assessment can refine a general treatment concept when it is applied in cases in which tumors do not respond to conventional chemo-radiation treatment. For solid tumors, which do not respond to classical treatment, and especially for rare tumors without an established protocol rapid microcalorimetric drug response testing presents an elegant novel approach to test alternative therapeutic approaches. While improved treatment concepts have led to improved outcome over the past decades, the prognosis of high risk disease is still poor and rethinking of clinical trial design is necessary. A small patient population combined with the necessity to assess experimental therapies for rare solid tumors rather at the time of diagnosis than in relapsed or refractory patients provides great challenges. The possibility to rapidly compare established protocols with innovative therapeutics presents an elegant novel approach to refine and personalize treatment. View Full-Text
Keywords: CAIX inhibitor; AQP1; rare pediatric cancer; isothermal calorimetry; drug susceptibility; clear cell renal carcinoma; organotypic slice culture CAIX inhibitor; AQP1; rare pediatric cancer; isothermal calorimetry; drug susceptibility; clear cell renal carcinoma; organotypic slice culture
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Gros, S.J.; Holland-Cunz, S.G.; Supuran, C.T.; Braissant, O. Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry–Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors. Int. J. Mol. Sci. 2019, 20, 4984.

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