Targeting CDK2 Confers Vulnerability to Lenvatinib Via Driving Senescence in Anaplastic Thyroid Cancer DOI Creative Commons
Ben Ma, Youzhou Sang, Xiaoxue Du

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

Anaplastic thyroid cancer (ATC) is the most lethal tumor arising from follicular epithelium. Lenvatinib an off-label use option for ATC patients in many countries but approved prescription Japan. However, lenvatinib resistance a substantial clinical challenge. Clinical samples including lenvatinib-resistant tumors are used to build patient-derived cells and xenografts. High-throughput drug screening synergy analyses performed identify effective combination partner lenvatinib. Cellular functions detected by cell senescence, apoptosis, cycle, viability colony formation assays. CDK2 inhibition showed significant synthetic lethality with via inhibiting G1/S transition inducing senescence ATC. High expression of associated poor outcomes patients. increased protein cells. Mechanistically, inhibited degradation reducing CDK2's interaction RACK1-FBW7 complex, which involved ubiquitination subsequent proteasomal CDK2. Combination inhibitors trials (Dinaciclib or PF-07104091) markedly suppressed growth xenograft patient. The findings support therapy strategy inhibitor high expression.

Язык: Английский

Improving the response to lenvatinib in partial responders using a Constrained-Disorder-Principle-based second-generation artificial intelligence-therapeutic regimen: a proof-of-concept open-labeled clinical trial DOI Creative Commons

Tal Sigawi,

Ram Gelman,

Ofra Maimon

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Июль 30, 2024

Introduction The main obstacle in treating cancer patients is drug resistance. Lenvatinib treatment poses challenges due to loss of response and the common dose-limiting adverse events (AEs). Constrained-disorder-principle (CDP)-based second-generation artificial intelligence (AI) systems introduce variability into regimens offer a potential strategy for enhancing efficacy. This proof-of-concept clinical trial aimed assess impact personalized algorithm-controlled therapeutic regimen on lenvatinib effectiveness tolerability. Methods A 14-week open-label, non-randomized was conducted with five receiving lenvatinib—an AI-assisted application tailored each patient, which physician approved. study assessed changes tumor through FDG-PET-CT markers quality life via EORTC QLQ-THY34 questionnaire, AEs, laboratory evaluations. app monitored adherence. Results At 14 weeks follow-up, disease control rate (including following outcomes: complete response, partial stable disease) 80%. scan-based RECIST v1.1 PERCIST criteria showed 40% an additional patients. One patient experienced progressing disease. Of participants thyroid cancer, 75% reduction thyroglobulin levels, 60% all decrease neutrophil-to-lymphocyte ratio during treatment. Improvement median social support score among utilizing system supports ancillary benefit intervention. No grade 4 AEs or functional deteriorations were recorded. Summary results this open-labeled suggest that CDP-based AI system-generated recommendations may improve manageable AEs. Prospective controlled studies are needed determine efficacy approach.

Язык: Английский

Процитировано

7

Progress in the Application of Novel Nanomaterials in Targeted Therapy for Liver Cancer DOI Creative Commons
Xin Wei,

Weihua Cao,

Shiyu Wang

и другие.

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 2623 - 2643

Опубликована: Март 1, 2025

In recent years, nanobiotechnology, widely used in hepatoma, holds great promise for improving targeted hepatocarcinoma therapy. On account of the unique properties low toxicity, good tolerance, biocompatibility, and biodegradability new nanomaterials, a drug delivery system (TDDS) has been constructed, which can boost therapeutic effect hepatoma-targeted drugs, reduce minimize off target reactions by enhancing permeability retention (EPR) active targeting, thus existing liver cancer therapy strategies. Different nanoparticles have their own advantages disadvantages. They be loaded with multiple drugs on same nanoparticle also surface modified each other to achieve synergistic anti-tumor effects. This essay provides comprehensive overview current status hepatocarcinoma, nanoparticles' structure, disadvantages nanoparticle, application progress cancer. We hope provide basis future clinical hepatoma using nanotechnology.

Язык: Английский

Процитировано

0

NOVA2 regulates the properties of liver cancer stem cells and lenvatinib resistance in hepatocellular carcinoma via the Wnt pathway DOI Open Access

Jing-Zhu Cao,

Chao-Qun Wang,

Zheng Shi

и другие.

Journal of Gastrointestinal Oncology, Год журнала: 2024, Номер 15(4), С. 1674 - 1685

Опубликована: Авг. 1, 2024

The regulation of cancer stem cells (CSCs) is influenced by RNA-binding proteins (RBPs). present study sought to investigate the role NOVA2 in processes self-renewal, carcinogenesis, and lenvatinib resistance liver CSCs.

Язык: Английский

Процитировано

2

Strategies to enhance the response of liver cancer to pharmacological treatments DOI
José J.G. Marı́n, Rocı́o I.R. Macı́as, Maitane Asensio

и другие.

AJP Cell Physiology, Год журнала: 2024, Номер 327(1), С. C11 - C33

Опубликована: Май 6, 2024

In contrast to other types of cancers, there is no available efficient pharmacological treatment improve the outcomes patients suffering from major primary liver i.e., hepatocellular carcinoma and cholangiocarcinoma. This dismal situation partly due existence in these tumors many different synergistic mechanisms resistance, accounting for lack response patients, not only classical chemotherapy but also more modern agents based on inhibition tyrosine kinase receptors (TKIs) stimulation immune against tumor using checkpoint inhibitors (ICIs). review summarizes efforts develop strategies overcome this severe limitation, including searching novel drugs derived synthetic, semisynthetic, or natural products with vectorial properties therapeutic targets increase drug uptake reduce export cancer cells. Besides, immunotherapy a promising line research that already starting be implemented clinical practice. Although less successful than foreseen future strategy treating cancers considerable. Similarly, epigenetic highly promising. Many “epidrugs,” able act “writer,” “reader,” “eraser” players, are currently being evaluated preclinical studies. Finally, gene therapy broad field fight chemoresistance, impressive advances recently achieved manipulation. sum, although present still dismal, reason hope non-too-distant future.

Язык: Английский

Процитировано

1

Exosomes as novel tools for renal cell carcinoma therapy, diagnosis, and prognosis DOI Creative Commons

Amir Razavinia,

Abazar Razavinia,

Roya Jamshidi Khalife Lou

и другие.

Heliyon, Год журнала: 2024, Номер 10(12), С. e32875 - e32875

Опубликована: Июнь 1, 2024

BackgroundRenal Cell Carcinoma (RCC) stands as a formidable challenge within the field of oncology, despite considerable research endeavors. The advanced stages this malignancy present barriers to effective treatment and management.ObjectiveThis review aims explore potential exosomes in addressing diagnostic therapeutic challenges associated with RCC. Specifically, it investigates role biomarkers vehicles context RCC management.MethodsFor article, comprehensive literature search was conducted using databases such PubMed, employing relevant keywords identify articles pertinent objectives review. Initially, 200 were identified, which underwent screening remove duplicates assess relevance based on titles abstracts, followed by detailed examination full texts. From selected articles, data extracted synthesized address review's objectives. conclusions drawn thorough analysis findings. quality ensured through independent resolution discrepancies among multiple reviewers.ResultsExosomes demonstrate tools for early detection, prognosis, monitoring Their ability deliver various agents, small interfering RNAs, lncRNAs, chemotherapeutic drugs, immune-stimulating allows personalized approach management. By leveraging exosome-based technologies, precision efficacy strategies can be significantly enhanced.ConclusionDespite promising advancements enabled management RCC, further is necessary refine technologies validate their efficacy, safety, long-term benefits rigorous clinical trials. Embracing integral components diagnosis represents significant step towards improving patient outcomes persistent posed oncology.

Язык: Английский

Процитировано

1

Efficacy of Treatments After Lenvatinib in Patients with Advanced Renal Cell Carcinoma DOI
Justine Panian,

Caiwei Zhong,

Sharon H. Choi

и другие.

European Urology Focus, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

1

Targeting CDK2 Confers Vulnerability to Lenvatinib Via Driving Senescence in Anaplastic Thyroid Cancer DOI Creative Commons
Ben Ma, Youzhou Sang, Xiaoxue Du

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

Anaplastic thyroid cancer (ATC) is the most lethal tumor arising from follicular epithelium. Lenvatinib an off-label use option for ATC patients in many countries but approved prescription Japan. However, lenvatinib resistance a substantial clinical challenge. Clinical samples including lenvatinib-resistant tumors are used to build patient-derived cells and xenografts. High-throughput drug screening synergy analyses performed identify effective combination partner lenvatinib. Cellular functions detected by cell senescence, apoptosis, cycle, viability colony formation assays. CDK2 inhibition showed significant synthetic lethality with via inhibiting G1/S transition inducing senescence ATC. High expression of associated poor outcomes patients. increased protein cells. Mechanistically, inhibited degradation reducing CDK2's interaction RACK1-FBW7 complex, which involved ubiquitination subsequent proteasomal CDK2. Combination inhibitors trials (Dinaciclib or PF-07104091) markedly suppressed growth xenograft patient. The findings support therapy strategy inhibitor high expression.

Язык: Английский

Процитировано

0