Neuroblastoma

P2, N=118, Not yet recruiting, New Approaches to Neuroblastoma Therapy Consortium

P1, N=13, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting | N=20 --> 13

Our findings highlight the effectiveness of LP-WGS ctDNA CNA analysis as a promising approach for diagnosis and risk stratification of pediatric neuroblastic tumors, and for monitoring chemotherapy response. Particularly, ctDNA analysis is minimally invasive, rapid and cost-effective, which could bring additional benefits in pediatric practices.

P1/2, N=90, Recruiting, St. Jude Children's Research Hospital | Active, not recruiting --> Recruiting | N=46 --> 90

Structural analysis of multiple X-ray cocrystal structures enabled the design of analogs that demonstrated excellent kinome selectivity. Tumor regression was observed in efficacy studies of compound 25 in a CHP-134 neuroblastoma xenograft tumor model.

Importantly, knockdown of IGF2BP1 along with anti-GD2 immunotherapy induced a synergistic immunogenic effect and achieved a potent antitumor response in an HR-NB mouse model, with increased accumulation of effector CD8+ T cells and CD86+  macrophages but decreased MDSC numbers in the tumor microenvironment. Thus, disrupting NB cancer cell IGF2BP1-mediated immunosuppression is a potential approach for improving the efficacy of anti-GD2 immunotherapy towards HR-NBs.

Two cases with chromosomal aberrations in stromal cells were also identified. Expression of MYC protein was detected in 5 cases, of which 2 showed amplification of the MYC gene.

Additionally, CRISPR-Cas9-mediated knockdown of EPO resulted in the abrogation of cell proliferation, whereas EPOR knockdown showed no effect, suggesting that Epo promotes N2A cell proliferation through an EpoR-independent mechanism. Collectively, these findings highlight the potential of the N2A+Epo cell line as a model for identifying alternative tissue-protective Epo receptors.

BA and Qe, particularly in combination, protect neuronal cells from PQ-induced oxidative and mitochondrial damage by restoring redox balance, stabilizing mitochondria, regulating Ca²⁺ homeostasis and modulating apoptosis and attenuating irritation in the in ovo model. These results suggest that BA and Qe may be promising complementary therapeutics to attenuate neurotoxicity caused by environmental toxins.

Although NTRK-associated fusions are significant in various cancers and have led to the development of targeted therapies, such as larotrectinib and entrectinib, the specific molecular impact of atypical PRUNE2::NTRK2 fusion remains unclear. The PRUNE2::NTRK2 gene fusions described here express a non-functional TrkB protein, and it is unclear whether the PRUNE2 function is intact or affected.

Our findings demonstrate the first evidence of a dedicated ciliary trafficking machinery for ACE2. We provide compelling evidence that SARS-CoV-2 hijacks evolutionarily conserved ciliary trafficking pathways, with TULP3-dependent targeting of ACE2 to primary cilia serving as a determinant of viral host cell tropism and invasion. This work uncovers novel molecular mechanisms underpinning SARS-CoV-2 infection, and highlights the primary cilium as a critical nexus for viral entry.