> Detailanzeige
Hobor, Sebastijan;
Al Bakir, Maise;
Hiley, Crispin T.;
Skrzypski, Marcin;
Frankell, Alexander M.;
Bakker, Bjorn;
Watkins, Thomas B. K.;
Markovets, Aleksandra;
Dry, Jonathan R.;
Brown, Andrew P.;
van der Aart, Jasper;
van den Bos, Hilda;
Spierings, Diana;
Oukrif, Dahmane;
Novelli, Marco;
Chakrabarti, Turja;
Rabinowitz, Adam H.;
Ait Hassou, Laila;
Litière, Saskia;
Kerr, D. Lucas;
Tan, Lisa;
Kelly, Gavin;
Moore, David A.;
Renshaw, Matthew J.;
[...]
Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling
Teilen
Literatur-
verwaltung
Direktlink
Zur
Merkliste
Lösche von
Merkliste
Per Email teilen
Auf Twitter teilen
Auf Facebook teilen
Per Whatsapp teilen
- Medientyp: E-Artikel
- Titel: Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling
- Beteiligte: Hobor, Sebastijan; Al Bakir, Maise; Hiley, Crispin T.; Skrzypski, Marcin; Frankell, Alexander M.; Bakker, Bjorn; Watkins, Thomas B. K.; Markovets, Aleksandra; Dry, Jonathan R.; Brown, Andrew P.; van der Aart, Jasper; van den Bos, Hilda; Spierings, Diana; Oukrif, Dahmane; Novelli, Marco; Chakrabarti, Turja; Rabinowitz, Adam H.; Ait Hassou, Laila; Litière, Saskia; Kerr, D. Lucas; Tan, Lisa; Kelly, Gavin; Moore, David A.; Renshaw, Matthew J.; [...]
-
Erschienen:
Springer Science and Business Media LLC, 2024
- Erschienen in: Nature Communications, 15 (2024) 1
- Sprache: Englisch
- DOI: 10.1038/s41467-024-47606-9
- ISSN: 2041-1723
- Entstehung:
- Anmerkungen:
- Beschreibung: AbstractThe phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.
- Zugangsstatus: Freier Zugang