Delving into the Latest Updates on Roblitinib with Synapse

In 2020, breast cancer surpassed lung cancer as the most common cancer in the world for the first time. Due to the resistance of some breast cancer cell lines to apoptosis, the therapeutic effect of anti-breast cancer drugs is limited. According to recent report, the susceptibility of breast cancer cells to ferroptosis affects the progress, prognosis and drug resistance of breast cancer. For instance, roblitinib induces ferroptosis of trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells by diminishing fibroblast growth factor receptor 4 (FGFR4) expression, thereby augmenting the susceptibility of these cells to HER2-targeted therapies. In tamoxifen-resistant breast cancer cells, Fascin exacerbates their resistance by repressing solute carrier family 7 member 11 (SLC7A11) expression, which in turn heightens their responsiveness to tamoxifen. In recent years, Chinese herbs extracts and therapeutic drugs have been demonstrated to elicit ferroptosis in breast cancer cells by modulating a spectrum of regulatory factors pertinent to ferroptosis, including SLC7A11, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long chain family member 4 (ACSL4), and haem oxygenase 1 (HO-1). Here, we review the roles and mechanisms of Chinese herbal extracts and therapeutic drugs in regulating ferroptosis in breast cancer, providing potential therapeutic options for anti-breast cancer.

01 Dec 2024·American Journal of Physiology-Lung Cellular and Molecular Physiology

Identification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis

Article

Author: Jaillet, Madeleine ; Justet, Aurélien ; Balayev, Agshin ; Poté, Nicolas ; Boghanim, Tiara ; Ghanem, Mada ; Mailleux, Arnaud ; Vadel, Aurélie ; Joannes, Audrey ; Mordant, Pierre ; Mal, Hervé ; Adams, Taylor ; Cazes, Aurélie ; Crestani, Bruno ; Vasarmidi, Eirini ; Hachem, Mouna

FGFR4 has been reported to have antifibrotic effects in the liver. We aimed to determine the involvement of FGFR4 during IPF. Our data suggest that FGFR4 exerts profibrotic properties by enhancing TGF-β signaling in vitro. However, the inhibition of FGFR4 is not sufficient to prevent the development of pulmonary fibrosis in vivo. To our knowledge, this is the first study to assess the profibrotic action of FGFR4 during pulmonary fibrosis.

01 Apr 2024·Cellular Oncology

The leukemia inhibitory factor regulates fibroblast growth factor receptor 4 transcription in gastric cancer

Article

Author: Cari, Luigi ; Sepe, Valentina ; Bordoni, Martina ; Urbani, Ginevra ; Massa, Carmen ; Monti, Maria Chiara ; Rapacciuolo, Pasquale ; Bellini, Rachele ; Fiorucci, Stefano ; Zampella, Angela ; Donini, Annibale ; Lupia, Antonio ; Distrutti, Eleonora ; Marchianò, Silvia ; Di Giorgio, Cristina ; Ullah, Khan Rana Sami ; Rosselli, Rosalinda ; Catalanotti, Bruno ; Morretta, Elva ; Moraca, Federica ; Natalizi, Nicola ; De Gregorio, Rosa ; Graziosi, Luigina ; Biagioli, Michele

AbstractPurposeThe gastric adenocarcinoma (GC) represents the third cause of cancer-related mortality worldwide, and available therapeutic options remain sub-optimal. The Fibroblast growth factor receptors (FGFRs) are oncogenic transmembrane tyrosine kinase receptors. FGFR inhibitors have been approved for the treatment of various cancers and a STAT3-dependent regulation of FGFR4 has been documented in the H.pylori infected intestinal GC. Therefore, the modulation of FGFR4 might be useful for the treatment of GC.MethodsTo investigate wich factors could modulate FGFR4 signalling in GC, we employed RNA-seq analysis on GC patients biopsies, human patients derived organoids (PDOs) and cancer cell lines.ResultsWe report that FGFR4 expression/function is regulated by the leukemia inhibitory factor (LIF) an IL-6 related oncogenic cytokine, in JAK1/STAT3 dependent manner. The transcriptomic analysis revealed a direct correlation between the expression of LIFR and FGFR4 in the tissue of an exploratory cohort of 31 GC and confirmed these findings by two external validation cohorts of GC. A LIFR inhibitor (LIR-201) abrogates STAT3 phosphorylation induced by LIF as well as recruitment of pSTAT3 to the promoter of FGFR4. Furthermore, inhibition of FGFR4 by roblitinib or siRNA abrogates STAT3 phosphorylation and oncogentic effects of LIF in GC cells, indicating that FGFR4 is a downstream target of LIF/LIFR complex. Treating cells with LIR-201 abrogates oncogenic potential of FGF19, the physiological ligand of FGFR4.ConclusionsTogether these data unreveal a previously unregnized regulatory mechanism of FGFR4 by LIF/LIFR and demonstrate that LIF and FGF19 converge on the regulation of oncogenic STAT3 in GC cells.Graphical abstract

100 Deals associated with Roblitinib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Phase 2	SG	Novartis Pharma AG	29 Dec 2014
Hepatocellular Carcinoma	Phase 2	ES	Novartis Pharma AG	29 Dec 2014
Hepatocellular Carcinoma	Phase 2	FR	Novartis Pharma AG	29 Dec 2014
Hepatocellular Carcinoma	Phase 2	DE	Novartis Pharma AG	29 Dec 2014
Hepatocellular Carcinoma	Phase 2	IT	Novartis Pharma AG	29 Dec 2014
Hepatocellular Carcinoma	Phase 2	US	Novartis Pharma AG	29 Dec 2014
Malignant Solid Neoplasm	Phase 2	US	Beijing Novartis Pharma Co. Ltd.	29 Dec 2014
Malignant Solid Neoplasm	Phase 2	FR	Novartis Pharma AG	29 Dec 2014
Hepatocellular Carcinoma	Preclinical	JP	Novartis Pharma AG	29 Dec 2014
Hepatocellular Carcinoma	Preclinical	KR	Novartis Pharma AG	29 Dec 2014

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02325739 (AACR2017)	Phase 2	Hepatocellular Carcinoma	172	NVP-FGF401	stprphtbqm(vmqoegtrjw) = dreeejcbbe whfgjdsfzm (vjgxmiwieb )	-	01 Jul 2017
NCT02325739 (AACR2017)	Phase 1/2	FGFR4 positive Neoplasms	67	FGF401	(xpsxntzfii) = whfglpbvnp psgowsflmh (scimnbujti ) View more	Positive	01 Jul 2017