2019
DOI: 10.1016/j.ccell.2019.09.007
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Paradigms for Precision Medicine in Epichaperome Cancer Therapy

Abstract: Highlights d Pathologic protein networks and their engagement in clinic are monitored by imaging d Real-time tumor pharmacometric data are obtained at the level of individual tumors d Theranostic and clinical assay combined provide quantitative tumor measurements d The platform provides dose and schedule information for epichaperome targeting

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Cited by 48 publications
(112 citation statements)
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“…1C). However, several drugs, including gemcitabine (GEM), trametinib, a MAPK/ERK kinase (MEK)-1/2 inhibitor, and PU-H71, a heatshock protein (HSP)-90 inhibitor with specificity for tumor HSP90 variants (11)(12)(13)(14), significantly reduced tumor growth when compared to control.…”
Section: Resultsmentioning
confidence: 99%
“…1C). However, several drugs, including gemcitabine (GEM), trametinib, a MAPK/ERK kinase (MEK)-1/2 inhibitor, and PU-H71, a heatshock protein (HSP)-90 inhibitor with specificity for tumor HSP90 variants (11)(12)(13)(14), significantly reduced tumor growth when compared to control.…”
Section: Resultsmentioning
confidence: 99%
“…For example, PU-H71 kinetically selects for epichaperome-integrated HSP90; no epichaperome IHC assay exists and histologic HSP90 expression is not predictive. Tumor avidity for PU-H71 tracer predicts pharmacodynamics and efficacy for PU-H71 [ 7 , 8 , 49 , 68 , 69 , 86 ] and other small molecule drugs targeting the HSP90 ATPase and interfering with epichaperome formation [ 8 , 49 ].…”
Section: Drug Tracer Imaging To Guide Patient Selectionmentioning
confidence: 99%
“…Drug tracer imaging can assay tumor pharmacokinetics, including (1) tumor drug concentrations as a function of time post-drug administration and (2) tumor occupancy by therapeutic drug doses [ 87 ]. Tumor pharmacokinetic data from patient imaging can be mathematically modeled for predicting the therapeutic dosage and schedule needed to achieve desired in vivo tumor drug concentration and tumor saturation levels [ 8 , 49 ] ( Figure 3 ). Imaging biodistribution can help to establish correlations with observed organ toxicity that might enable dosing strategies optimized for the therapeutic index [ 65 ].…”
Section: Tumor Pharmacokinetics For Image-guided Dosing Designmentioning
confidence: 99%
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“…Radiodiagnostics, such as PET imaging, has emerged as a vital component in precision medicine. [1][2][3][4][5][6][7] Several radiotracers have been used extensively for patient stratification and prognosis assessment in clinical settings. Besides, numerous radiotracers are being studied in clinical trials or are under pre-clinical evaluation.…”
Section: Introductionmentioning
confidence: 99%