AZD4547 targets the FGFR/Akt/SOX2 axis to overcome paclitaxel resistance in head and neck cancer

Aytatli, Abdülmelik; Barlak, Neslişah; Şanli, Fatma; Çağlar, Hasan Onur; Gündoğdu, Betül; Tatar, Arzu; Ittmann, Michael; Karataş, Ömer Faruk

doi:10.1007/s13402-021-00645-6

Cited by 14 publications

(12 citation statements)

References 92 publications

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“…Selective inhibitors include futibatinib, 341 , 342 erdafitinib, 343 LY2874455, 344 , 345 pemigatinib, 195 , 346 infigratinib, 347 , 348 AZD4547, 349 , 350 rogaratinib, 351 , 352 E7090, 353 , 354 and debio 1347. 355 , 356 Selective inhibitors target FGFR to inhibit downstream signaling pathways, thereby acting as cancer suppressors.…”

Section: Fgfr Acts As a Therapeutic Targetmentioning

confidence: 99%

FGFR families: biological functions and therapeutic interventions in tumors

Liu,

Huang,

Yan

et al. 2023

MedComm

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There are five fibroblast growth factor receptors (FGFRs), namely, FGFR1–FGFR5. When FGFR binds to its ligand, namely, fibroblast growth factor (FGF), it dimerizes and autophosphorylates, thereby activating several key downstream pathways that play an important role in normal physiology, such as the Ras/Raf/mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase, phosphoinositide 3‐kinase (PI3K)/AKT, phospholipase C gamma/diacylglycerol/protein kinase c, and signal transducer and activator of transcription pathways. Furthermore, as an oncogene, FGFR genetic alterations were found in 7.1% of tumors, and these alterations include gene amplification, gene mutations, gene fusions or rearrangements. Therefore, FGFR amplification, mutations, rearrangements, or fusions are considered as potential biomarkers of FGFR therapeutic response for tyrosine kinase inhibitors (TKIs). However, it is worth noting that with increased use, resistance to TKIs inevitably develops, such as the well‐known gatekeeper mutations. Thus, overcoming the development of drug resistance becomes a serious problem. This review mainly outlines the FGFR family functions, related pathways, and therapeutic agents in tumors with the aim of obtaining better outcomes for cancer patients with FGFR changes. The information provided in this review may provide additional therapeutic ideas for tumor patients with FGFR abnormalities.

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Section: Fgfr Acts As a Therapeutic Targetmentioning

confidence: 99%

FGFR families: biological functions and therapeutic interventions in tumors

Liu,

Huang,

Yan

et al. 2023

MedComm

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“…The cell culture medium was refreshed every 3–4 days. After 10–12 days, colonies were fixed, stained, and visualized as described previously (Aytatli et al, 2022).…”

Section: Methodsmentioning

confidence: 99%

Overexpression of POFUT1 promotes malignant phenotype and mediates perineural invasion in head and neck squamous cell carcinoma

Barlak,

Kusdemir,

Gumus

et al. 2023

Cell Biology International

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Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive neoplasms, which requires more effective prevention and treatment modalities. Previous studies found that protein O‐fucosyltransferase 1 (POFUT1) upregulation promotes carcinogenesis, although the potential roles, underlying molecular mechanisms, and biological implications of POFUT1 in HNSCC were not investigated. In this study, in silico analyses referred POFUT1 as a potential oncogene in HNSCC. Further analysis of tumor and normal tissue samples as well as HNSCC cells with quantitative real‐time polymerase chain reaction, Western blot analysis, and immunohistochemistry showed significant overexpression of POFUT1 in HNSCC clinical tumor tissue specimens and cell lines compared to corresponding controls. In vitro investigations revealed that overexpression of POFUT1 promoted phenotypes associated with cancer aggressiveness and its knockdown in HNSCC cells suppressed those phenotypes. Further xenograft experiments demonstrated that POFUT1 is an oncogene in vivo for HNSCC. Immunohistochemical analysis with human clinical samples and cancer cell‐dorsal root ganglion ex‐vivo coculture model showed that deregulation of POFUT1 is involved in the perineural invasion of HNSCC cells. These results suggest POFUT1 expression as a potential prognostic marker for patients with head and neck cancer and highlight its potential as a target for HNSCC therapy, although more molecular clues are needed to better define the functions of POFUT1 related to HNSCC carcinogenesis.

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“…For instance, a preclinical study with TAS102-treated cells and a clinical study with HNSCC patients [ 129 , 130 ] highlighted FGF signaling alterations as relevant drivers of tumorigenesis. Confirming this, preclinical assessments have indicated curcumin as a potential natural compound to inhibit 4NQO-induced tumorigenesis via modulation of the bFGF/FGFR-2 axis [ 131 ] and AZD4547 as a new chemical molecule targeting the FGFR/Akt/SOX2 axis to overcome paclitaxel resistance in HNSCC [ 132 ]. Furthermore, alterations in angiogenesis-modulating genes can influence therapy outcomes and tumor progression.…”

Section: Bfgf and Cancermentioning

confidence: 98%

Role of Basic Fibroblast Growth Factor in Cancer: Biological Activity, Targeted Therapies, and Prognostic Value

Ardizzone

Bova

Casili

et al. 2023

Cells

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Cancer is the leading cause of death worldwide; thus, it is necessary to find successful strategies. Several growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), and transforming growth factor beta (TGF-β), are involved in the main processes that fuel tumor growth, i.e., cell proliferation, angiogenesis, and metastasis, by activating important signaling pathways, including PLC-γ/PI3/Ca2+ signaling, leading to PKC activation. Here, we focused on bFGF, which, when secreted by tumor cells, mediates several signal transductions and plays an influential role in tumor cells and in the development of chemoresistance. The biological mechanism of bFGF is shown by its interaction with its four receptor subtypes: fibroblast growth factor receptor (FGFR) 1, FGFR2, FGFR3, and FGFR4. The bFGF–FGFR interaction stimulates tumor cell proliferation and invasion, resulting in an upregulation of pro-inflammatory and anti-apoptotic tumor cell proteins. Considering the involvement of the bFGF/FGFR axis in oncogenesis, preclinical and clinical studies have been conducted to develop new therapeutic strategies, alone and/or in combination, aimed at intervening on the bFGF/FGFR axis. Therefore, this review aimed to comprehensively examine the biological mechanisms underlying bFGF in the tumor microenvironment, the different anticancer therapies currently available that target the FGFRs, and the prognostic value of bFGF.

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AZD4547 targets the FGFR/Akt/SOX2 axis to overcome paclitaxel resistance in head and neck cancer

Cited by 14 publications

References 92 publications

FGFR families: biological functions and therapeutic interventions in tumors

FGFR families: biological functions and therapeutic interventions in tumors

Overexpression of POFUT1 promotes malignant phenotype and mediates perineural invasion in head and neck squamous cell carcinoma

Role of Basic Fibroblast Growth Factor in Cancer: Biological Activity, Targeted Therapies, and Prognostic Value

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