Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer.

Chewei Anderson ChangJayu JenShaowen JiangAzin SayadArvind Singh Mer Kevin R Brown Allison M L NixonAvantika DhabariaKwan Ho Tang David Venet Christos Sotiriou Jiehui DengKwok-Kin WongSylvia AdamsPeter MeynAdriana HeguyJane A Skok Aristotelis TsirigosBeatrix UeberheideJason MoffatAbhyudai SinghBenjamin Haibe-Kains Alireza Khodadadi-JamayranBenjamin G Neel

Published in: Cancer discovery (2022)

DTPs are implicated in resistance to anticancer therapies, but their ontogeny and vulnerabilities remain unclear. We find that HER2 TKI-DTPs emerge from stochastically arising primed cells ("pre-DTPs") that engage either of two distinct transcriptional programs upon TKI exposure. Our results provide new insights into DTP ontogeny and potential therapeutic vulnerabilities. This article is highlighted in the In This Issue feature, p. 873.

Keyphrases

tyrosine kinase
induced apoptosis
advanced non small cell lung cancer
cell cycle arrest
chronic myeloid leukemia
public health
machine learning
gene expression
transcription factor
endoplasmic reticulum stress
emergency department
oxidative stress
cell death
signaling pathway
heat shock
heat shock protein