Development of miRNA-based PROTACs targeting Lin28 for breast cancer therapy DOI Creative Commons

Jianfei Xu,

Xiaoran Zhao, Xingxing Liang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(38)

Published: Sept. 18, 2024

Lin28, a highly conserved carcinogenic protein, plays an important role in the generation of cancer stem cells, contributing to unfavorable prognosis patients. This RNA binding protein specifically binds pri/pre-microRNA (miRNA) lethal-7 (let-7), impeding its miRNA maturation. The reduced expression tumor suppressor let-7 fosters development and progression-related traits such as proliferation, invasion, metastasis, drug resistance. We report series miRNA-based Lin28A-miRNA proteolysis-targeting chimeras (Lin28A-miRNA-PROTACs) designed efficiently degrade Lin28A through ubiquitin-proteasome–dependent mechanism, resulting up-regulation mature family. augmented levels matured miRNAs further exert inhibitory effects on cell proliferation migration, increase sensitivity chemotherapy. In mouse ectopic model, Lin28A-miRNA-PROTAC demonstrates substantial efficacy inhibiting growth. When combined with tamoxifen, tumors exhibit gradual regression. study displays effective PROTACs inhibit growth, providing promising therapeutic avenue for treatment therapy.

Language: Английский

Potential of the nanoplatform and PROTAC interface to achieve targeted protein degradation through the Ubiquitin–Proteasome system DOI

Hanshu Xie,

Chao Zhang

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116168 - 116168

Published: Feb. 1, 2024

Language: Английский

Citations

5
PROTAC: Novel degradable approach for different targets to treat breast cancer DOI Creative Commons
Zhenjie Wang, Siyao Che,

Zhiqiang Yu

et al.

European Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: 198, P. 106793 - 106793

Published: May 11, 2024

The revolutionary Proteolysis Targeting Chimera (PROTACs) have the exciting potential to reshape pharmaceutical industry landscape by leveraging ubiquitin-proteasome system for targeted protein degradation. Breast cancer, most prevalent cancer in women, could be treated using PROTAC therapy. Although substantial work has been conducted, there isn't yet a comprehensive overview or progress update on therapy breast cancer. Hence, this article, we've compiled recent research focusing different target proteins, such as estrogen receptor (ER), BET, CDK, HER2, PARP, EZH2, etc. This resource aims serve guide future PROTAC-based treatment design.

Language: Английский

Citations

5
Defeating MYC with drug combinations or dual-targeting drugs DOI
Philip E. Thompson, Jake Shortt

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(6), P. 490 - 502

Published: May 22, 2024

Language: Английский

Citations

5
Novel gene therapy for drug-resistant melanoma: Synergistic combination of PTEN plasmid and BRD4 PROTAC-loaded lipid nanocarriers DOI Creative Commons

Aishwarya Saraswat,

Hari Priya Vemana, Vikas V. Dukhande

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2024, Volume and Issue: 35(3), P. 102292 - 102292

Published: July 31, 2024

Patients suffering from BRAF mutant melanoma have tumor recurrence within merely 7 months of treatment with a potent inhibitor (BRAFi) like vemurafenib. It has been proven that diverse molecular pathways driving BRAFi resistance converge to activation c-Myc in melanoma. Therefore, we identified novel combinatorial therapeutic strategy by targeting loss phosphatase and tensin homolog deleted on chromosome 10 (PTEN) suppressor gene upregulated BRD4 oncoprotein as Myc-dependent vulnerabilities drug-resistant Being promising targets, decided concomitantly deliver PTEN plasmid targeted PROteolysis-TArgeting Chimera (ARV) drug the "undruggable" BRAFi-resistant Since ARV are distinct their physicochemical properties, fabricated PTEN-plasmid loaded lipid nanoparticles (PL-NANO) ARV-825-loaded nanoliposomes (AL-NANO) yield mean particle size less than 100 nm greater 99% encapsulation efficiency for each payload. Combination PL-NANO AL-NANO displayed synergistic growth inhibition substantial apoptosis vitro two-dimensional three-dimensional models. Importantly, simultaneous delivery achieved significant upregulation expression levels degradation protein ultimately downregulate cells. Altogether, nanocarriers delivering this lethal cocktail stands one-of-a-kind therapy target undruggable oncogene melanoma.Graphical abstract

Language: Английский

Citations

5
Development of miRNA-based PROTACs targeting Lin28 for breast cancer therapy DOI Creative Commons

Jianfei Xu,

Xiaoran Zhao, Xingxing Liang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(38)

Published: Sept. 18, 2024

Lin28, a highly conserved carcinogenic protein, plays an important role in the generation of cancer stem cells, contributing to unfavorable prognosis patients. This RNA binding protein specifically binds pri/pre-microRNA (miRNA) lethal-7 (let-7), impeding its miRNA maturation. The reduced expression tumor suppressor let-7 fosters development and progression-related traits such as proliferation, invasion, metastasis, drug resistance. We report series miRNA-based Lin28A-miRNA proteolysis-targeting chimeras (Lin28A-miRNA-PROTACs) designed efficiently degrade Lin28A through ubiquitin-proteasome–dependent mechanism, resulting up-regulation mature family. augmented levels matured miRNAs further exert inhibitory effects on cell proliferation migration, increase sensitivity chemotherapy. In mouse ectopic model, Lin28A-miRNA-PROTAC demonstrates substantial efficacy inhibiting growth. When combined with tamoxifen, tumors exhibit gradual regression. study displays effective PROTACs inhibit growth, providing promising therapeutic avenue for treatment therapy.

Language: Английский

Citations

4