Furthermore, SLC2A1 expression was linked to responsiveness to dasatinib and vincristine, suggesting potential therapeutic relevance. MLPS and SLC2A1 offer promising tools for individualized prognosis prediction and targeted therapy in HCC, providing new opportunities to improve patient outcomes.

In vivo, trastuzumab-vincristine conjugates led to remarkable efficacy when compared to two standards of care, with complete tumor regression just 9 days after single administration. This highlights the untapped potential of the chemotherapeutic arsenal toward the development of novel ADC.

Furthermore, Ephexin4 knockdown exacerbated vincristine-induced chromosome misalignment, which was prevented by re-expressing the wild-type but not S41A Ephexin4...Our results suggest that Ephexin4 undergoes phosphorylation at Ser41 in cell division, and the phosphorylation is required for chromosome alignment through RhoG activation. Combined with mitosis-targeting agents, inhibition of Ephexin4 phosphorylation may represent a novel strategy for cancer chemotherapy.

Our ER stress model performed a valuable prediction on breast cancer patients.

P1/2, N=122, Recruiting, AtlasMedx, Incorporated | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Oct 2026 | Trial primary completion date: Jan 2025 --> Aug 2026

Most interestingly, the triplet treatment exhibited a safer toxicological profile than the doublet (vinorelbine plus carboplatin) currently applied in the clinical practice. Altogether, these preclinical data support the possibility of repurposing pirfenidone in combination with vinorelbine or with vinorelbine plus carboplatin for NSCLC perioperative treatment, improving therapeutic efficacy while reducing toxicity.

This study confirms the therapeutic efficacy of P(NIPAM-co-AM)/Hyp as a TLR3 agonist and provides a new study direction for immunotherapy strategy and vaccine development by targeting parasites.

P2, N=28, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2027 --> Aug 2027 | Trial primary completion date: Dec 2026 --> Aug 2026

ICIs is effective in the treatment of lung cancer, which can obviously reduce the tumor load and has high safety. In addition, the maximum tumor diameter and LDH are risk factors that affect the poor curative effect of lung cancer. High PNI level and ICIs treatment are helpful to improve the effect of lung cancer, and early monitoring is helpful to guide the treatment plan and evaluate the treatment effect.

Moreover, immunofluorescence analysis and western-blot assays potentiated, that selected analogues inhibited the inflammatory cytokine TNF-α induced activation of MK2 on cellular and molecular levels in HNSCC cells. In conclusion, this study presents novel MK2-inhibitors and opens the avenue for further pre-clinical and clinical efficacy evaluation of developed PfBS analogues in the treatment of HNSCC.Communicated by Ramaswamy H. Sarma.

GNA combined with the MCL-1 inhibitor MIK665 potently suppressed the proliferation of MDS cells...GNA-induced apoptosis was attenuated in either p65 KO or Fas KO cells. These results demonstrate that GNA inhibited tubulin polymerization and induced apoptosis of MDS cells through upregulation of Fas expression mediated by the NF-κB signaling pathway, suggesting a chemotherapeutic strategy for MDS by microtubule dynamics disruption.

These findings suggest that CD40 agonists are promising immunotherapeutic candidates for pediatric B-ALL, warranting further clinical investigations to improve patient outcomes in CD40-expressing B-ALL.

P4, N=514, Not yet recruiting, Anhui Chest Hospital; Anhui Chest Hospital

P3, N=118, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting

P1/2, N=74, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting

These findings present potential actionable genomic markers of vincristine neuropathy and offer opportunities for tailored interventions to improve vincristine safety in children with cancer. This study is registered with ClinicalTrials.gov under the title National Active Surveillance Network and Pharmacogenomics of Adverse Drug Reactions in Children (ID NCT00414115, registered on December 21, 2006).

Molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) studies showed that OA had a binding free energy that is comparable with that of vincristine (-52.76, and -63.56 kcal/mol, respectively)...The binding energy and stability at the active site of 17βHSD1 recorded in this study indicate that OA exhibited profound inhibitory potential. OA could be a good scaffold for developing new anti-breast cancer drugs.

Melatonin also reduced inflammation, decreased reactive astrocytes and microglia, and prevented neurodegeneration and demyelination in the spinal cord. Importantly, melatonin did not affect VCR's cytotoxic activity in cancer cells.

Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer.

P2, N=75, Recruiting, Beijing Sanbo Brain Hospital | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P3, N=12997, Completed, Medicines Development for Global Health | Active, not recruiting --> Completed

P4, N=72, Active, not recruiting, Ain Shams University

The results showed that allometric scaling, ABCB1-rs1128503 genotype, and posaconazole (POS) significantly improved the PopPK model fit...No significant effects on VIPN were observed for CYP3A5 (rs776746), CYP3A4 (rs2242480), CEP72 (rs924607), or various ABCB1 variants (rs1128503, rs2032582, rs1045642, rs4728709, rs4148737, and rs10276036), nor with the co-administration of fluconazole or dasatinib. In summary, co-administration of POS increased VCR exposure by 0.4-fold and raised the risk of VIPN, with an occurrence probability generally exceeding 0.7. Therapeutic drug monitoring of VCR in clinical practice may be necessary to enable appropriate dose adjustments and individualized treatment.

This study provides pre-clinical evidence that AKT inhibitors combined with PI3K inhibitors, cisplatin, or vincristine exhibit additive/synergistic anti-MB activity, and lower doses could be used. The latter also applied to one MB line grown as spheroids, further supporting their future potential use.

P=N/A, N=83, Recruiting, Children's Oncology Group | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=700, Recruiting, Prince of Songkla University | Not yet recruiting --> Recruiting

During the clinical courses of four patients, cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone were administered to all patients, but it resulted in incomplete responses in all four patients. Over a 7.5-year median follow-up, one patient developed autoimmune-related diseases, while one developed other hematological malignancy, resulting in death. To our knowledge, this is the first report of recurrent HAVCR2 germline mutations in Japanese patients, suggesting the necessity for long-term follow-up.

The Lucena 1 cell line, derived from the human chronic myeloid leukemia cell line K562 under selective pressure of vincristine supplementation, exhibits multidrug resistance (MDR)...This study offers new insights into the MDR phenotype and its multifactorial consequences in cellular pathways. Thus, unraveling the mechanisms of MDR holds promise for innovating cancer models and antitumor targeted strategies, since inhibiting the P-glycoprotein (P-gp)/ABCB1 protein is not always an effective approach given the associated treatment toxicity.

To investigate this, we performed omics analysis of BCP-ALL cells that survived a 30-day vincristine chemotherapy treatment while in co-culture with bone marrow stromal cells...Glycoproteomics confirmed glycosite-specific modulation of cell surface and lysosomal proteins in drug-tolerant BCP-ALL cells, including HLA-DRA, CD38, LAMP1 and PPT1. We conclude that drug-tolerant persister leukemia cells that grow under continuous chemotherapy stress have characteristic glycotraits that correlate with and perhaps contribute to their ability to survive and could be tested as neoantigens in drug-resistant leukemia.

Thus, the SNP rs924607 in the CEP72 gene is associated with increased VIPN incidence in female patients with aggressive B-NHL treated with CHOP chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT00052936, submission date: 2005-06-23, EudraCT Number: 2010-019587-36.

The results of the present study indicate that the concurrent use of siRNA and vinorelbine holds substantial promise as a therapeutic approach to overcome ABCB1-mediated multidrug resistance (MDR) in breast cancer. It is necessary to conduct comprehensive clinical trials to determine the true effectiveness of this combination therapy.

No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN.

Moreover, compound 32 significantly inhibited the tumour growth of the HepG2 xenograft in a nude mouse model by oral gavage without apparent toxicity. These results demonstrated that some 2-substituted 2, 3- dihydroquinazolin-4(1H)-one derivatives bearing phenyl, biphenyl, naphthyl or indolyl side chain at C2-position might be potentially novel antitumor agents as tubulin polymerization inhibitors.

On follow-up after initiation of vincristine/actinomycin/cyclophosphamide chemotherapy, the tumors showed partial and complete clinical response, consistent with typical upfront chemotherapy responsiveness of ARMS with the classic FOXO1 rearrangement. We conclude that PAX3::MAML3 is a novel variant fusion of ARMS, which displays a methylation signature distinct from BSNS despite sharing similar PAX3 fusions. These findings highlight the utility of methylation profiling in classifying ARMS with non-canonical fusions.

P=N/A, N=137, Completed, St. Jude Children's Research Hospital | Suspended --> Completed | N=200 --> 137

Increased Cyr61 expression appears to reduce the chemosensitivity of B-ALL cell to vincristine (VCR) and daunorubicin (DNR) through autophagy under hypoxia. Notably, inhibition of Cyr61 restores the chemosensitivity of B-ALL cells to both chemotherapeutic agents. This study is the first time to report that hypoxia decreases the chemosensitivity of B-ALL cells by inducing Cyr61 production, suggesting that targeting Cyr61 or its associated pathways could potentially improve the clinical response of B-ALL patients.

P2, N=47, Active, not recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

It highlights the potential effectiveness of sulfamethoxazole/trimethoprim and albendazole in managing such cases. Further research is warranted to elucidate optimal management strategies and improve outcomes in similar clinical scenarios.

Furthermore, in vitro tubulin polymerization inhibition studies revealed that compound 6e showed comparable activity with podophyllotoxin. Finally, in silico molecular docking studies of compounds 6e, 6j, 6n and podophyllotoxin on α,β-tubulin (pdb id 1SA0) revealed that compound 6n showed excellent binding energies and inhibition constants compared with podophyllotoxin.

Subsequent studies revealed that PTA-1 disrupts microtubule organization and inhibits tubulin polymerization. Our results suggest that PTA-1 is a potent drug with cytotoxicity to various cancer cells, induces apoptosis and cell cycle arrest, and inhibits tubulin polymerization, indicating that PTA-1 is an attractive drug for future clinical cancer treatment.

P=N/A, N=74, Recruiting, Children's Oncology Group | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

P3, N=118, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting