biorxiv.org

DUSP4 knockdown in BRAF V600E mutant colorectal cancer induces cell cycle arrest and halts tumor growth

Oncogenic signaling in cancer cells is essential for proliferation, and its disruption, either through inhibition or overactivation, can provide therapeutic opportunities. Dual specificity phosphatase 4 (DUSP4), a negative regulator of the MAPK pathway that dephosphorylates ERK, has been proposed as a potential target; however, its therapeutic relevance has not been evaluated in vivo. In this study, we show that DUSP4 knock-down induces G1 cell cycle arrest and reduces proliferation in BRAFV600E-mutant and BRAF inhibitor-resistant colorectal cancer models, both in vitro and in vivo, and induces a rapid DUSP5-mediated adaptive response. While treatment achieved tumor stasis indicating disease control, it did not yield tumor regression, suggesting that DUSP4 may have limited efficacy as a monotherapy target in cancer. ### Competing Interest Statement All authors are full time employees at Boehringer Ingelheim RCV.

biorxiv.org

DUSP4 knockdown in BRAF V600E mutant colorectal cancer induces cell cycle arrest and halts tumor growth

Oncogenic signaling in cancer cells is essential for proliferation, and its disruption, either through inhibition or overactivation, can provide therapeutic opportunities. Dual specificity phosphatase 4 (DUSP4), a negative regulator of the MAPK pathway that dephosphorylates ERK, has been proposed as a potential target; however, its therapeutic relevance has not been evaluated in vivo. In this study, we show that DUSP4 knock-down induces G1 cell cycle arrest and reduces proliferation in BRAFV600E-mutant and BRAF inhibitor-resistant colorectal cancer models, both in vitro and in vivo, and induces a rapid DUSP5-mediated adaptive response. While treatment achieved tumor stasis indicating disease control, it did not yield tumor regression, suggesting that DUSP4 may have limited efficacy as a monotherapy target in cancer. ### Competing Interest Statement All authors are full time employees at Boehringer Ingelheim RCV.

biorxiv.org

Science-Fiction-Autor über KI: "Wir entscheiden selbst über Utopie oder Dystopie"

Der Österreicher Ralph Neumüller räumt zum zweiten Mal in Folge den Deutschen Science-Fiction-Preis ab. Er will das Genre als gesellschaftliches Experimentierfeld sichtbarer machen

derstandard.at

Harvard Funding Cuts Endanger the Massive Fruit Fly Database That Powers Genetic Research | News | The Harvard Crimson

FlyBase lost a multimillion dollar grant when the Trump administration cut off Harvard’s federal funding in May. Now the repository is laying off staff — and researchers worldwide are worried.

thecrimson.com

Die wichtigste Datenbank über die Fruchtfliege steht vor dem Aus.

Forscher weltweit sind auf eine zentrale Datenbank mit Erkenntnissen zu Drosophila angewiesen. Deren Finanzierung steht vor dem Aus. Wegen Donald Trump. Warum uns das nicht gleichgültig sein sollte.

faz.net

FlyBase:Contribute to FlyBase - FlyBase Wiki

wiki.flybase.org

indiecharts - Singles

Österreichs wöchentliche Independent-Charts, gevotet von den österreichischen Indie-DJs

indiecharts.at

Ralph Alexander Neumüller (13.02.2025)

Literatopia - eure Welt der Literatur! Rezensionen, Forum, Interviews, Events und vieles mehr ...

literatopia.de

Kommando Elefant ft. Ralph Alexander Neumüller - Traurige Maschinen

YouTube video by kommandoelefant

youtube.com

Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers

Zongertinib, a covalent HER2 inhibitor, is active in HER2-driven preclinical models and patients and effectively targets HER2 oncogenic signaling while sparing wild-type EGFR, resulting in potent inhi...

aacrjournals.org