Journal article

SLC7A11 Is a Superior Determinant of APR-246 (Eprenetapopt) Response than TP53 Mutation Status

Kenji M Fujihara, Mariana Corrales Benitez, Carlos S Cabalag, Bonnie Z Zhang, Hyun S Ko, David S Liu, Kaylene J Simpson, Ygal Haupt, Lara Lipton, Sue Haupt, Wayne A Phillips, Nicholas J Clemons

MOLECULAR CANCER THERAPEUTICS | AMER ASSOC CANCER RESEARCH | Published : 2021

Abstract

APR-246 (eprenetapopt) is in clinical development with a focus on hematologic malignancies and is promoted as a mutant-p53 reactivation therapy. Currently, the detection of at least one TP53 mutation is an inclusion criterion for patient selection into most APR-246 clinical trials. Preliminary results from our phase Ib/II clinical trial investigating APR-246 combined with doublet chemotherapy [cisplatin and 5-fluorouracil (5-FU)] in metastatic esophageal cancer, together with previous preclinical studies, indicate that TP53 mutation status alone may not be a sufficient biomarker for APR-246 response. This study aims to identify a robust biomarker for response to APR-246. Correlation analysis..

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Grants

Awarded by NMHRC


Awarded by Cancer Council Victoria


Awarded by Department of Health and Human Services through the Victorian Cancer Agency, Victoria, Australia


Awarded by Department of Health and Human Services acting through the Victorian Cancer Agency Fellowship


Funding Acknowledgements

We thank Aprea Therapeutics for providing the APR-246 used in this study. Thanks to Lars Abrahmsen from Aprea Therapeutics for critical discussion of the manuscript. The diagrams in Figs. 4 and 5 were created using BioRender.com. This work was supported by an NMHRC Project Grant (APP1120293 to W.A. Phillips, N.J. Clemons, Y. Haypt), a Grand-In-Aid (APP1156945 to N.J. Clemons, W.A. Phillips) from the Cancer Council Victoria, and a Translational Research Project grant (TRP15012 to W.A. Phillips, N.J. Clemons, L. Lipton) from the Department of Health and Human Services through the Victorian Cancer Agency, Victoria, Australia. N.J. Clemons is supported by a Fellowship (MCRF16002) from the Department of Health and Human Services acting through the Victorian Cancer Agency Fellowship. K.M. Fujihara is supported by an Australian Research Training Program (RTP) Scholarship. C.S. Cabalag is the recipient of, and supported by, The Alan & Kate Gibson Research Fellowship, 2018 for The Victorian Centre for Functional Genomics. K.J. Simpson is funded by the Australian Cancer Research Foundation (ACRF), Phenomics Australia (PA), through funding from the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS) program, the Peter MacCallum Cancer Centre Foundation, and the University of Melbourne Research Collaborative Infrastructure Program (MCRIP).