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- W4386316213 abstract "Chemotherapy is pivotal in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC). Technical advances unveiled a high degree of inter- and intratumoral heterogeneity. We hypothesized that intratumoral heterogeneity (ITH) impacts response to gemcitabine treatment and demands specific targeting of resistant subclones.Using single cell-derived cell lines (SCDCLs) from the classical cell line BxPC3 and the basal-like cell line Panc-1, we addressed the effect of ITH on response to gemcitabine treatment.Individual SCDCLs of both parental tumor cell populations showed considerable heterogeneity in response to gemcitabine. Unsupervised PCA including the 1,000 most variably expressed genes showed a clustering of the SCDCLs according to their respective sensitivity to gemcitabine treatment for BxPC3, while this was less clear for Panc-1. In BxPC3 SCDCLs, enriched signaling pathways EMT, TNF signaling via NfKB, and IL2STAT5 signaling correlated with more resistant behavior to gemcitabine. In Panc-1 SCDCLs MYC targets V1 and V2 as well as E2F targets were associated with stronger resistance. We used recursive feature elimination for Feature Selection in order to compute sets of proteins that showed strong association with the response to gemcitabine. The optimal protein set calculated for Panc-1 comprised fewer proteins in comparison to the protein set determined for BxPC3. Based on molecular profiles, we could show that the gemcitabine-resistant SCDCLs of both BxPC3 and Panc-1 are more sensitive to the BET inhibitor JQ1 compared to the respective gemcitabine-sensitive SCDCLs.Our model system of SCDCLs identified gemcitabine-resistant subclones and provides evidence for the critical role of ITH for treatment response in PDAC. We exploited molecular differences as the basis for differential response and used these for more targeted therapy of resistant subclones." @default.
- W4386316213 created "2023-09-01" @default.
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- W4386316213 date "2023-08-31" @default.
- W4386316213 modified "2023-09-26" @default.
- W4386316213 title "Molecular profiling and specific targeting of gemcitabine-resistant subclones in heterogeneous pancreatic cancer cell populations" @default.
- W4386316213 cites W1497915798 @default.
- W4386316213 cites W1527742565 @default.
- W4386316213 cites W1831050183 @default.
- W4386316213 cites W1968812902 @default.
- W4386316213 cites W1976033223 @default.
- W4386316213 cites W1981216064 @default.
- W4386316213 cites W1987191607 @default.
- W4386316213 cites W1996536755 @default.
- W4386316213 cites W2000932071 @default.
- W4386316213 cites W2009949436 @default.
- W4386316213 cites W2017789254 @default.
- W4386316213 cites W2023560061 @default.
- W4386316213 cites W2041535798 @default.
- W4386316213 cites W2041993682 @default.
- W4386316213 cites W2045446356 @default.
- W4386316213 cites W2060484997 @default.
- W4386316213 cites W2062921699 @default.
- W4386316213 cites W2100751052 @default.
- W4386316213 cites W2107077050 @default.
- W4386316213 cites W2115186999 @default.
- W4386316213 cites W2120572492 @default.
- W4386316213 cites W2151253787 @default.
- W4386316213 cites W2153879016 @default.
- W4386316213 cites W2154790710 @default.
- W4386316213 cites W2157923000 @default.
- W4386316213 cites W2166994863 @default.
- W4386316213 cites W2169895148 @default.
- W4386316213 cites W2169961966 @default.
- W4386316213 cites W2170776626 @default.
- W4386316213 cites W2219978888 @default.
- W4386316213 cites W2285093314 @default.
- W4386316213 cites W2323326409 @default.
- W4386316213 cites W2340761255 @default.
- W4386316213 cites W2389623734 @default.
- W4386316213 cites W2508385150 @default.
- W4386316213 cites W2531403772 @default.
- W4386316213 cites W2537132940 @default.
- W4386316213 cites W2594738913 @default.
- W4386316213 cites W2597696518 @default.
- W4386316213 cites W2620721366 @default.
- W4386316213 cites W2755850587 @default.
- W4386316213 cites W2766266723 @default.
- W4386316213 cites W2768163228 @default.
- W4386316213 cites W2782791713 @default.
- W4386316213 cites W2803724995 @default.
- W4386316213 cites W2807651426 @default.
- W4386316213 cites W2883315636 @default.
- W4386316213 cites W2899760200 @default.
- W4386316213 cites W2903623792 @default.
- W4386316213 cites W2914759417 @default.
- W4386316213 cites W2954999982 @default.
- W4386316213 cites W2991106430 @default.
- W4386316213 cites W2999027176 @default.
- W4386316213 cites W3005253564 @default.
- W4386316213 cites W3009738007 @default.
- W4386316213 cites W3015049042 @default.
- W4386316213 cites W3037738062 @default.
- W4386316213 cites W3045051771 @default.
- W4386316213 cites W3081852640 @default.
- W4386316213 cites W3090067576 @default.
- W4386316213 cites W3103188996 @default.
- W4386316213 cites W3119455371 @default.
- W4386316213 cites W3119775561 @default.
- W4386316213 cites W3136918052 @default.
- W4386316213 cites W3177861273 @default.
- W4386316213 cites W3178066990 @default.
- W4386316213 cites W4206501087 @default.
- W4386316213 cites W4211181525 @default.
- W4386316213 cites W4224257265 @default.
- W4386316213 cites W4225288568 @default.
- W4386316213 cites W4308025599 @default.
- W4386316213 cites W4310639010 @default.
- W4386316213 cites W4320496828 @default.
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- W4386316213 doi "https://doi.org/10.3389/fonc.2023.1230382" @default.
- W4386316213 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37719017" @default.
- W4386316213 hasPublicationYear "2023" @default.
- W4386316213 type Work @default.