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A phenocopy signature of TP53 loss predicts response to chemotherapy

Bakhtiar, Hamza ; Sharifi, Marina N ; Helzer, Kyle T ; Shi, Yue ; Bootsma, Matthew L ; Shang, Tianfu A ; Chrostek, Matthew R ; Berg, Tracy J LU ; Carson Callahan, S and Carreno, Viridiana , et al. (2024) In NPJ precision oncology 8(1).
Abstract

In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with... (More)

In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts.

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publishing date
type
Contribution to journal
publication status
published
subject
in
NPJ precision oncology
volume
8
issue
1
article number
220
publisher
Springer Nature
external identifiers
  • scopus:85205958937
  • pmid:39358429
ISSN
2397-768X
DOI
10.1038/s41698-024-00722-7
language
English
LU publication?
no
additional info
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
id
79c3ce72-7c25-4945-9eda-ff235b1149e7
date added to LUP
2026-02-09 14:24:08
date last changed
2026-05-19 18:20:10
@article{79c3ce72-7c25-4945-9eda-ff235b1149e7,
  abstract     = {{<p>In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts.</p>}},
  author       = {{Bakhtiar, Hamza and Sharifi, Marina N and Helzer, Kyle T and Shi, Yue and Bootsma, Matthew L and Shang, Tianfu A and Chrostek, Matthew R and Berg, Tracy J and Carson Callahan, S and Carreno, Viridiana and Blitzer, Grace C and West, Malinda T and O'Regan, Ruth M and Wisinski, Kari B and Sjöström, Martin and Zhao, Shuang G}},
  issn         = {{2397-768X}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{NPJ precision oncology}},
  title        = {{A phenocopy signature of TP53 loss predicts response to chemotherapy}},
  url          = {{http://dx.doi.org/10.1038/s41698-024-00722-7}},
  doi          = {{10.1038/s41698-024-00722-7}},
  volume       = {{8}},
  year         = {{2024}},
}