Sugita, Mayumi; Wilkes, David C; Bareja, Rohan; Eng, Kenneth W; Nataraj, Sarah; Jimenez-Flores, Reyna A; Yan, LunBiao; De Leon, Jeanne Pauline; Croyle, Jaclyn A; Kaner, Justin; Merugu, Swathi; Sharma, Sahil; MacDonald, Theresa Y; Noorzad, Zohal; Panchal, Palak; Pancirer, Danielle; Cheng, Shuhua; Xiang, Jenny Z; Olson, Luke; Van Besien, Koen; ... (2021). Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia. NPJ precision oncology, 5(1), p. 44. Springer Nature 10.1038/s41698-021-00183-2
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The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that further investigation of epichaperome inhibitors in patients with abundant baseline epichaperome levels is warranted.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) |
UniBE Contributor: |
Rubin, Mark Andrew |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2397-768X |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Marla Rittiner |
Date Deposited: |
24 Jan 2022 11:48 |
Last Modified: |
05 Dec 2022 16:00 |
Publisher DOI: |
10.1038/s41698-021-00183-2 |
PubMed ID: |
34040147 |
BORIS DOI: |
10.48350/163459 |
URI: |
https://boris.unibe.ch/id/eprint/163459 |
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