HGF/MET Signaling in Malignant Brain Tumors

Mulcahy, Elizabeth; Colόn, Rossymar Rivera; Abounader, Roger

doi:10.3390/ijms21207546

Cited by 26 publications

(23 citation statements)

References 137 publications

(164 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GAB1 is a scaffolding protein involved in recruiting additional signaling proteins such as PI3K, SHP2, and p120RasGap. It is involved in many EGFR signaling outputs, and is the predominant mechanism linking EGFR to PI3K/Akt signaling [ 52 , 53 ].…”

Section: Mechanisms Of Egfr Pathway Activationmentioning

confidence: 99%

Updated Insights on EGFR Signaling Pathways in Glioma

Opriţa

Baloi

Staicu

et al. 2021

IJMS

107

View full text Add to dashboard Cite

Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.

show abstract

Section: Mechanisms Of Egfr Pathway Activationmentioning

confidence: 99%

Updated Insights on EGFR Signaling Pathways in Glioma

Opriţa

Baloi

Staicu

et al. 2021

IJMS

107

View full text Add to dashboard Cite

show abstract

“…Active, cleaved HGF binds the alpha and the beta chain to induce receptor dimerization and subsequent activation [ 45 ]. Activated, autophoshorylated MET recruits and activates downstream effectors that include SRC kinases and, via RAS, the RAF/MAPK and PI3K/AKT pathways [ 46 ].…”

Section: Rtk As Drivers In Gbmmentioning

confidence: 99%

Tyrosine Kinase Inhibitors in Adult Glioblastoma: An (Un)Closed Chapter?

Aldaz

Arozarena

2021

Cancers

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most common and lethal form of malignant brain tumor. GBM patients normally undergo surgery plus adjuvant radiotherapy followed by chemotherapy. Numerous studies into the molecular events driving GBM highlight the central role played by the Epidermal Growth Factor Receptor (EGFR), as well as the Platelet-derived Growth Factor Receptors PDGFRA and PDGFRB in tumor initiation and progression. Despite strong preclinical evidence for the therapeutic potential of tyrosine kinase inhibitors (TKIs) that target EGFR, PDGFRs, and other tyrosine kinases, clinical trials performed during the last 20 years have not led to the desired therapeutic breakthrough for GBM patients. While clinical trials are still ongoing, in the medical community there is the perception of TKIs as a lost opportunity in the fight against GBM. In this article, we review the scientific rationale for the use of TKIs targeting glioma drivers. We critically analyze the potential causes for the failure of TKIs in the treatment of GBM, and we propose alternative approaches to the clinical evaluation of TKIs in GBM patients.

show abstract

“…High MET intensity correlates with high WHO grade and shorter PFS and OS [ 256 , 257 ]. Other reviews have provided comprehensive information on HGF/MET functions and modes of action in GB [ 256 , 258 , 259 , 260 ]. An overview of clinical trials in GB patients targeting MET is given in Table 5 .…”

Section: Receptor Tyrosine Kinase Inhibitors (Rtkis) For Gb Therapymentioning

confidence: 99%

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

et al. 2021

View full text Add to dashboard Cite

Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

show abstract

HGF/MET Signaling in Malignant Brain Tumors

Cited by 26 publications

References 137 publications

Updated Insights on EGFR Signaling Pathways in Glioma

Updated Insights on EGFR Signaling Pathways in Glioma

Tyrosine Kinase Inhibitors in Adult Glioblastoma: An (Un)Closed Chapter?

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

Contact Info

Product

Resources

About