Here, we generated a mutant RSPO2 furin domain that retains high-affinity LGR4/5/6 binding without any signaling activity. RSPO2 furin mutant peptibodies conjugated with pyrrolobenzodiazepine dimer (PBD) or camptothecin derivative (CPT2) yielded potent, target-selective cytotoxicity in LGR4/5/6-positive CRC and high-risk NB cell lines in vitro and robust antitumor activity in vivo.

1 day ago

Journal

RSPO2 (R-Spondin 2) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)

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.

1 day 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

Comprehensive molecular analyses for diagnosis and treatment guidance in an adult neuroblastoma patient. (PubMed, Oncologist)

Comprehensive molecular analysis and MTB discussion revealed several potential treatment targets, leading to subsequent treatment including dinutuximab beta, nivolumab, cabozantinib, I-131-mIBG radionuclide therapy and alpelisib, unfortunately, all followed by disease progression. This case demonstrates the potential of comprehensive molecular analysis including methylation profiling for diagnosis and treatment guidance in rare tumors. Additional research is urgently required to improve outcomes in elderly patients with neuroblastoma.

1 day ago

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

NTRK (Neurotrophic receptor tyrosine kinase)

NTRK fusion

Opdivo (nivolumab) • Piqray (alpelisib) • Cabometyx (cabozantinib tablet) • Qarziba (dinutuximab beta)

ZRANB1 depletion inhibits neuroblastoma progression by destabilizing MYCN through EZH2-mediated deubiquitination. (PubMed, Cell Biol Toxicol)

This study identifies ZRANB1 as an upstream deubiquitinase that stabilizes EZH2, thereby indirectly maintaining MYCN stability in MYCN-amplified neuroblastoma. These findings establish a ZRANB1-EZH2-MYCN regulatory axis and highlight ZRANB1 as a promising therapeutic target in MYCN-amplified NB.

1 day ago

Journal

MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ZRANB1 (Zinc Finger RANBP2-Type Containing 1)

MYCN amplification

Telomere damage enhances immunogenicity of neuroblastoma and accelerates response to anti-PD-L1 treatment. (PubMed, Oncoimmunology)

Mechanistically, 6-thio-dG combined with anti-PD-L1 treatment induced cGAS and PD-L1 expression and promoted immune cell infiltration in the tumors. Our findings suggest that 6-thio-dG treatment activates the cGAS-STING pathway in neuroblastoma and that induction of telomere dysfunction in combination with immune checkpoint blockade boosts intratumoral immune cell infiltration and improves survival in a high-risk neuroblastoma mouse model.

1 day ago

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

MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • STING (stimulator of interferon response cGAMP interactor 1) • CGAS (Cyclic GMP-AMP Synthase)

PD-L1 expression

Concurrent naxitamab and lorlatinib in a patient with refractory high-risk neuroblastoma: a case report. (PubMed, Front Oncol)

Mild adverse events occurred during the combined immunotherapy, including transient hypotension managed with intravenous fluids and abdominal and leg pain that improved with analgesics. In conclusion, our case showed that combination therapy with naxitamab and lorlatinib may improve long-term outcomes and reduce chemotherapy-related toxicity.

1 day ago

Journal • IO biomarker

ALK (Anaplastic lymphoma kinase)

ALK mutation

oncoReveal™ Multi-Cancer with CNV & RNA Fusion Panel

Lorbrena (lorlatinib) • Danyelza (naxitamab-gqgk)

Growth hormone-releasing hormone attenuates amyloid deposition and neuroinflammation in Alzheimer's disease models. (PubMed, Cell Death Dis)

Overall, these findings indicate that GHRH and its analog MR-409 exert neuroprotective effects by modulating key pathological features of AD, including neurodegeneration, impaired neurogenesis, neuroinflammation, and oxidative stress. Given their ability to modulate multiple pathological pathways, GHRH agonists may represent promising therapeutic candidates for AD and other neurodegenerative disorders.

2 days ago

Journal

KEAP1 (Kelch Like ECH Associated Protein 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • IGF1 (Insulin-like growth factor 1)

RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells. (PubMed, iScience)

The RUVBL proteins form a complex with ATPase activity that has broad cellular functions and we demonstrate that pharmacological inhibition of this protein complex results in a strong reduction of MYC(N) signaling, cell-cycle arrest, DNA damage, and apoptosis. We confirmed the association with MYCN and identified the RUVBL genes as independent prognostic biomarkers in human primary neuroblastoma data.

4 days ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • RUVBL1 (RuvB Like AAA ATPase 1)

MYCN amplification

CCL2: A double-edged sword in neuroblastoma, with a critical role in MYCN-amplified tumors. (PubMed, Transl Oncol)

Understanding its complex biology is critical for the development of novel immunotherapies aimed at restoring effective anti-tumor immune responses, particularly in high-risk MYCN-amplified NB. Targeting the CCL2 axis represents a promising strategy to improve NB patient outcomes.

4 days ago

Review • Journal • IO biomarker

MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CCL2 (Chemokine (C-C motif) ligand 2) • CCR2 (C-C Motif Chemokine Receptor 2)

MYCN amplification

Capsaicin attenuates methylglyoxal-induced neurotoxicity via the ATF4-Sestrin2 signaling and direct scavenging of methylglyoxal. (PubMed, Neurotoxicology)

Collectively, these findings demonstrate that capsaicin confers protection against MGO-induced neuronal toxicity through coordinated activation of the TRPV1-PERK-ATF4-Sestrin2 stress-response pathway and direct chemical neutralization of MGO. Our results identify capsaicin as a dual-function modulator of carbonyl stress and suggest its potential relevance for therapeutic strategies targeting MGO-associated neurotoxicity.

6 days ago

Journal

ATF4 (Activating Transcription Factor 4) • TCF4 (Transcription Factor 4)

Enzyme-mimetic nanodots catalytically alleviate stress-induced hypertension via anti-neuroinflammation effects. (PubMed, J Nanobiotechnology)

Mechanistically, Mn@CDs downregulate NOX2/NOX4 within RVLM region and alleviate oxidative stress, thus reversing microglial activation and reducing neuronal apoptosis. This work presents a non-pharmaceutical catalytic strategy based on biocompatible Mn@CDs nanozymes targeting the RVLM ROS-neuroinflammation axis for SIH.

7 days ago

Journal

BCL2 (B-cell CLL/lymphoma 2) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • IL1B (Interleukin 1, beta) • NOX4 (NADPH Oxidase 4) • CAT (Catalase)