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GENE:

GAB1 (GRB2 Associated Binding Protein 1)

News alerts, weekly reports and conference planners

Role of Surrogate Immunohistochemistry Markers in CNS Tumors in the Era of Molecular Diagnostics With Recent Updates. (PubMed, Adv Anat Pathol)

The review emphasizes that when interpreted alongside histomorphology and conventional markers, surrogate immunohistochemistry can significantly reduce reliance on molecular testing, expedite diagnosis, and improve accessibility of precision diagnostics. Standardization, validation, and awareness of pitfalls remain essential to maximizing their clinical utility in neuropathology practice.

2 days ago

Journal

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • ATRX (ATRX Chromatin Remodeler) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • BCOR (BCL6 Corepressor) • YAP1 (Yes associated protein 1) • VIM (Vimentin) • STAT6 (Signal transducer and activator of transcription 6) • L1CAM (L1 cell adhesion molecule) • DUX4 (Double Homeobox 4) • FOXR2 (Forkhead Box R2) • GAB1 (GRB2 Associated Binding Protein 1)

TP53 mutation • BRAF V600E • BRAF V600 • IDH mutation + BRAF V600E

Modeling acquired TKI resistance and effective combination therapeutic strategies in murine RET+ lung adenocarcinoma. (PubMed, Cancer Lett)

Oncogenic RET gene rearrangements drive a subset of lung adenocarcinomas (LUAD) and the tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib are approved therapeutics. By contrast, upfront treatment with selpercatinib and crizotinib in orthotopic tumors yielded complete elimination of 7 of 9 TR.1 tumors and both deepened and prolonged the duration of response in TR.2 tumors. The findings provide new insight into mechanisms of acquired resistance through bypass signaling and highlight the therapeutic benefit of simultaneous upfront blockade of driver oncogenes and dominant resistance mechanisms in LUAD.

9 days ago

Preclinical • Journal

HER-2 (Human epidermal growth factor receptor 2) • RET (Ret Proto-Oncogene) • NRG1 (Neuregulin 1) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • NRP1 (Neuropilin 1) • TRIM24 (Tripartite Motif Containing 24) • GAB1 (GRB2 Associated Binding Protein 1)

MET amplification • RET rearrangement

Xalkori (crizotinib) • Retevmo (selpercatinib) • Gavreto (pralsetinib)

2ms

Bacterial Cyclodipeptides Inhibit Invasiveness and Metastasis Progression in the Triple-Negative Breast Cancer MDA-MB-231 Mouse Model. (PubMed, Molecules)

CDPs significantly decreased the migratory and invasive capabilities of the MDA-MB-231 cell line, outperforming methotrexate (MTX)...Additionally, genes related to EMT, invasiveness, and immune modulation-including PTEN, SNAIL, CXCL1, BRCA1, GADD45A, and PD-L1-were dysregulated in the livers of TNBC-bearing mice; however, CDP treatment restored their expression more effectively than MTX. These findings suggest that the anti-metastatic effects of CDPs in the TNBC xenograft model involve modulation of the Akt/mTOR/S6K pathway, EMT, invasiveness, and immune modulation, highlighting their potential for further preclinical development.

2 months ago

Preclinical • Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • VIM (Vimentin) • CXCL1 (Chemokine (C-X-C motif) ligand 1) • GAB1 (GRB2 Associated Binding Protein 1)

methotrexate

4ms

Mechanism of SHP2 activation by bis-Tyr-phosphorylated Gab1. (PubMed, Structure)

In addition to eliciting changes in SH2 domain dynamics, the peptide reorganizes their relative orientations to generate a new SH2-SH2 interface. Our data suggest an active conformation for SHP2 that is also applicable to the hematopoietic cell-specific SHP1 (PTPN6), shedding light on the activation mechanism of both enzymes and paving the way for the development of novel compounds to modulate SHP2 activity.

4 months ago

Journal

PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • GAB1 (GRB2 Associated Binding Protein 1)

4ms

RASH3D19 mediates RAS activation through a positive feedback loop in KRAS-mutant cancer. (PubMed, Nat Cell Biol)

Genetic deletion of RASH3D19 in mutant KRAS-expressing cancer cells exhibits growth retardation in vitro, in vivo and sensitized pancreatic ductal adenocarcinoma and colorectal cancer cells, organoids and xenografts to mutant KRAS inhibitors, suppressing feedback reactivation of RAS pathways. Therapeutic targeting of RASH3D19 is expected to lead to tumour debulking and alleviating resistance to KRAS inhibitors in mutant KRAS-expressing cancers.

4 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ETS1 (ETS Proto-Oncogene 1) • SH3D19 (SH3 Domain Containing 19) • GAB1 (GRB2 Associated Binding Protein 1) • MIR222 (MicroRNA 222)

KRAS mutation

4ms

MET signaling drives acquired resistance to erdafitinib in muscle-invasive bladder cancer cells. (PubMed, Cell Death Dis)

Combined inhibition of FGFR1 and MET significantly suppressed tumor growth in resistant cells. These findings establish MET amplification and GAB1-SHP2 signaling as central mediators of erdafitinib resistance in FGFR1-amplified MIBC and support dual FGFR1/MET targeting as a promising therapeutic strategy.

4 months ago

Preclinical • Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • HGF (Hepatocyte growth factor) • GAB1 (GRB2 Associated Binding Protein 1)

MET amplification

Balversa (erdafitinib)

7ms

Selective EV Protein Sorting and Pathway Perturbation in AML Upon Synergistic FLT3 and Hedgehog Pathway Inhibition. (PubMed, J Extracell Vesicles)

These findings were corroborated by comparative proteomics of EVs derived from AML patients and healthy donors. Ribosomal and ErbB signalling pathway proteins may play an important role in microenvironmental modulation by EVs, and Crenolanib treatment potentially acts by interfering with leukaemia niche formation.

7 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • RPS26 (Ribosomal Protein S26) • GAB1 (GRB2 Associated Binding Protein 1) • RPL27A (Ribosomal Protein L27a)

FLT3 mutation

crenolanib (ARO-002)

9ms

Phosphoinositide 3-kinase regulates wild-type RAS signaling to confer resistance to KRAS inhibition. (PubMed, bioRxiv)

We further demonstrate that inhibiting PI3K enhances sensitivity to mutant-specific KRAS inhibitors in PDAC cells, including cells with clinically identified PIK3CA mutations. Our findings refine RAS-PI3K signaling paradigms, reveal that PI3K-driven wild-type RAS activation drives resistance to KRAS inhibition, and illuminate new avenues for augmenting KRAS-targeted therapies in PDAC.

9 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • GAB1 (GRB2 Associated Binding Protein 1)

KRAS mutation • PIK3CA mutation • RAS wild-type

10ms

The Src family kinase inhibitor drug Dasatinib and glucocorticoids display synergistic activity against tongue squamous cell carcinoma and reduce MET kinase activity. (PubMed, Cell Commun Signal)

This work is the first to show a strong synergistic activity of Dasatinib in combination with clinically used glucocorticoids in solid tumors. Furthermore, the tyrosine kinase MET and its effector protein Gab1 are newly identified glucocorticoid targets. Given the extensive research on MET as a drug target in various cancers, our findings have the potential to advance future cancer treatments.

10 months ago

Journal

GAB1 (GRB2 Associated Binding Protein 1)

dasatinib • dexamethasone