Literature DB >> 32366671

First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer.

Mark P S Dunphy1, Christina Pressl2, Nagavarakishore Pillarsetty3,4, Milan Grkovski5, Shanu Modi6, Komal Jhaveri6, Larry Norton6, Bradley J Beattie5, Pat B Zanzonico3, Danuta Zatorska7, Tony Taldone7, Stefan O Ochiana7, Mohammad M Uddin7, Eva M Burnazi8, Serge K Lyashchenko8, Clifford A Hudis6, Jacqueline Bromberg6, Heiko M Schöder3, Josef J Fox3, Hanwen Zhang8, Gabriela Chiosis6,9, Jason S Lewis3,4,8,10, Steven M Larson3,4,7,10.   

Abstract

PURPOSE: 124I-PU-H71 is an investigational first-in-class radiologic agent specific for imaging tumor epichaperome formations. The intracellular epichaperome forms under cellular stress and is a clinically validated oncotherapeutic target. We conducted a first-in-human study of microdose 124I-PU-H71 for PET to study in vivo biodistribution, pharmacokinetics, metabolism, and safety; and the feasibility of epichaperome-targeted tumor imaging. EXPERIMENTAL
DESIGN: Adult patients with cancer (n = 30) received 124I-PU-H71 tracer (201±12 MBq, <25 μg) intravenous bolus followed by PET/CT scans and blood radioassays.
RESULTS: 124I-PU-H71 PET detected tumors of different cancer types (breast, lymphoma, neuroblastoma, genitourinary, gynecologic, sarcoma, and pancreas). 124I-PU-H71 was retained by tumors for several days while it cleared rapidly from bones, healthy soft tissues, and blood. Radiation dosimetry is favorable and patients suffered no adverse effects.
CONCLUSIONS: Our first-in-human results demonstrate the safety and feasibility of noninvasive in vivo detection of tumor epichaperomes using 124I-PU-H71 PET, supporting clinical development of PU-H71 and other epichaperome-targeted therapeutics. ©2020 American Association for Cancer Research.

Entities:  

Year:  2020        PMID： 32366671      PMCID： PMC7541604          DOI： 10.1158/1078-0432.CCR-19-3704

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  33 in total

Review 1.  Pharmacometrics at FDA: evolution and impact on decisions.

Authors:  J R Powell; J V S Gobburu
Journal:  Clin Pharmacol Ther       Date:  2007-05-30       Impact factor: 6.875

2.  Inhibition of Hsp90 Suppresses PI3K/AKT/mTOR Signaling and Has Antitumor Activity in Burkitt Lymphoma.

Authors:  Lisa Giulino-Roth; Herman J van Besien; Tanner Dalton; Jennifer E Totonchy; Anna Rodina; Tony Taldone; Alexander Bolaender; Hediye Erdjument-Bromage; Jouliana Sadek; Amy Chadburn; Matthew J Barth; Filemon S Dela Cruz; Allison Rainey; Andrew L Kung; Gabriela Chiosis; Ethel Cesarman
Journal:  Mol Cancer Ther       Date:  2017-06-15       Impact factor: 6.261

Review 3.  Chaperome heterogeneity and its implications for cancer study and treatment.

Authors:  Tai Wang; Anna Rodina; Mark P Dunphy; Adriana Corben; Shanu Modi; Monica L Guzman; Daniel T Gewirth; Gabriela Chiosis
Journal:  J Biol Chem       Date:  2018-11-08       Impact factor: 5.157

Review 4.  Clinical Evaluation and Biomarker Profiling of Hsp90 Inhibitors.

Authors:  Akira Yuno; Min-Jung Lee; Sunmin Lee; Yusuke Tomita; David Rekhtman; Brittni Moore; Jane B Trepel
Journal:  Methods Mol Biol       Date:  2018

5.  The epichaperome is an integrated chaperome network that facilitates tumour survival.

Authors:  Anna Rodina; Tai Wang; Pengrong Yan; Erica DaGama Gomes; Mark P S Dunphy; Nagavarakishore Pillarsetty; John Koren; John F Gerecitano; Tony Taldone; Hongliang Zong; Eloisi Caldas-Lopes; Mary Alpaugh; Adriana Corben; Matthew Riolo; Brad Beattie; Christina Pressl; Radu I Peter; Chao Xu; Robert Trondl; Hardik J Patel; Fumiko Shimizu; Alexander Bolaender; Chenghua Yang; Palak Panchal; Mohammad F Farooq; Sarah Kishinevsky; Shanu Modi; Oscar Lin; Feixia Chu; Sujata Patil; Hediye Erdjument-Bromage; Pat Zanzonico; Clifford Hudis; Lorenz Studer; Gail J Roboz; Ethel Cesarman; Leandro Cerchietti; Ross Levine; Ari Melnick; Steven M Larson; Jason S Lewis; Monica L Guzman; Gabriela Chiosis
Journal:  Nature       Date:  2016-10-05       Impact factor: 49.962

Review 6.  Molecular pathways: targeting hsp90--who benefits and who does not.

Authors:  Maurizio Scaltriti; Shaheenah Dawood; Javier Cortes
Journal:  Clin Cancer Res       Date:  2012-06-20       Impact factor: 12.531

7.  Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to Taxol.

Authors:  David B Solit; Andrea D Basso; Adam B Olshen; Howard I Scher; Neal Rosen
Journal:  Cancer Res       Date:  2003-05-01       Impact factor: 12.701

8.  Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71.

Authors:  Tony Taldone; Danuta Zatorska; Stefan O Ochiana; Peter Smith-Jones; Jacek Koziorowski; Mark P Dunphy; Pat Zanzonico; Alexander Bolaender; Jason S Lewis; Steven M Larson; Gabriela Chiosis; Naga Vara Kishore Pillarsetty
Journal:  J Labelled Comp Radiopharm       Date:  2016-01-25       Impact factor: 1.921

9.  Phase I and pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with refractory advanced cancers.

Authors:  Ramesh K Ramanathan; Merrill J Egorin; Julie L Eiseman; Suresh Ramalingam; David Friedland; Sanjiv S Agarwala; S Percy Ivy; Douglas M Potter; Gurkamal Chatta; Eleanor G Zuhowski; Ronald G Stoller; Cynthia Naret; Jianxia Guo; Chandra P Belani
Journal:  Clin Cancer Res       Date:  2007-03-15       Impact factor: 12.531

Review 10.  Heat shock protein 90 inhibitors in the treatment of cancer: current status and future directions.

Authors:  Komal Jhaveri; Stefan O Ochiana; Mark Ps Dunphy; John F Gerecitano; Adriana D Corben; Radu I Peter; Yelena Y Janjigian; Erica M Gomes-DaGama; John Koren; Shanu Modi; Gabriela Chiosis
Journal:  Expert Opin Investig Drugs       Date:  2014-03-26       Impact factor: 6.206
View more
  7 in total

1.  HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

Authors:  Takuya Osada; Erika J Crosby; Kensuke Kaneko; Joshua C Snyder; Joshua D Ginzel; Chaitanya R Acharya; Xiao-Yi Yang; Thomas J Polascik; Ivan Spasojevic; Rendon C Nelson; Amy Hobeika; Zachary C Hartman; Leonard M Neckers; Andre Rogatko; Philip F Hughes; Jiaoti Huang; Michael A Morse; Timothy Haystead; H Kim Lyerly
Journal:  Mol Cancer Ther       Date:  2021-10-21       Impact factor: 6.261

Review 2.  The penalty of stress - Epichaperomes negatively reshaping the brain in neurodegenerative disorders.

Authors:  Stephen D Ginsberg; Suhasini Joshi; Sahil Sharma; Gianny Guzman; Tai Wang; Ottavio Arancio; Gabriela Chiosis
Journal:  J Neurochem       Date:  2021-10-31       Impact factor: 5.372

3.  Measuring Tumor Epichaperome Expression Using [124I] PU-H71 Positron Emission Tomography as a Biomarker of Response for PU-H71 Plus Nab-Paclitaxel in HER2-Negative Metastatic Breast Cancer.

Authors:  Komal L Jhaveri; Carlos H Dos Anjos; Tony Taldone; Rui Wang; Elizabeth Comen; Monica Fornier; Jacqueline F Bromberg; Weining Ma; Sujata Patil; Anna Rodina; Nagavarakishore Pillarsetty; Susan Duggan; Sarhe Khoshi; Nathan Kadija; Gabriela Chiosis; Mark P Dunphy; Shanu Modi
Journal:  JCO Precis Oncol       Date:  2020-11-17

4.  Oncogenic HSP90 Facilitates Metabolic Alterations in Aggressive B-cell Lymphomas.

Authors:  M Nieves Calvo-Vidal; Nahuel Zamponi; Jan Krumsiek; Max A Stockslager; Maria V Revuelta; Jude M Phillip; Rossella Marullo; Ekaterina Tikhonova; Nikita Kotlov; Jayeshkumar Patel; Shao Ning Yang; Lucy Yang; Tony Taldone; Catherine Thieblemont; John P Leonard; Peter Martin; Giorgio Inghirami; Gabriela Chiosis; Scott R Manalis; Leandro Cerchietti
Journal:  Cancer Res       Date:  2021-09-03       Impact factor: 12.701

Review 5.  Heat Shock Proteins in Lymphoma Immunotherapy.

Authors:  Zarema Albakova; Yana Mangasarova; Alexander Sapozhnikov
Journal:  Front Immunol       Date:  2021-03-18       Impact factor: 7.561

Review 6.  The Unique Pharmacometrics of Small Molecule Therapeutic Drug Tracer Imaging for Clinical Oncology.

Authors:  Mark P S Dunphy; Nagavarakishore Pillarsetty
Journal:  Cancers (Basel)       Date:  2020-09-22       Impact factor: 6.639

7.  Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system.

Authors:  Alexander Bolaender; Danuta Zatorska; Huazhong He; Suhasini Joshi; Sahil Sharma; Chander S Digwal; Hardik J Patel; Weilin Sun; Brandon S Imber; Stefan O Ochiana; Maulik R Patel; Liza Shrestha; Smit K Shah; Shuo Wang; Rashad Karimov; Hui Tao; Pallav D Patel; Ananda Rodilla Martin; Pengrong Yan; Palak Panchal; Justina Almodovar; Adriana Corben; Andreas Rimner; Stephen D Ginsberg; Serge Lyashchenko; Eva Burnazi; Anson Ku; Teja Kalidindi; Sang Gyu Lee; Milan Grkovski; Bradley J Beattie; Pat Zanzonico; Jason S Lewis; Steve Larson; Anna Rodina; Nagavarakishore Pillarsetty; Viviane Tabar; Mark P Dunphy; Tony Taldone; Fumiko Shimizu; Gabriela Chiosis
Journal:  Nat Commun       Date:  2021-08-03       Impact factor: 14.919
  7 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.