Dataset Information

Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.

ABSTRACT:

Aim

This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer.

Materials & methods

We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice.

Results

Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combination of PTX-DCMs and AZD92921-DCMs exhibited strong synergistic effects in both cell line and in vivo without additional toxicity. Molecular studies demonstrated the synergistic modification in both IKB-α/NF-κB/Bcl-2 and EGFR/Akt pathways.

Conclusion

The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.

SUBMITTER: Wang XS

PROVIDER: S-EPMC6219431 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.

Wang Xin-Shuai XS Zhang Li L Li Xiaocen X Kong De-Jiu DJ Hu Xiao-Chen XC Ding Xue-Zhen XZ Yang Jun-Qiang JQ Zhao Meng-Qi MQ He Yixuan Y Lam Kit S KS Gao She-Gan SG Lin Tzu-Yin TY Li Yuanpei Y

Nanomedicine (London, England) 20180501 10

<h4>Aim</h4>This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer.<h4>Materials & methods</h4>We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice.<h4>Results</h4>Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combi ...[more]

PMID: 29874151

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Project description:PurposeThird-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated potent activity against TKI resistance mediated by EGFR T790M. We studied whether noninvasive genotyping of cell-free plasma DNA (cfDNA) is a useful biomarker for prediction of outcome from a third-generation EGFR-TKI, osimertinib.MethodsPlasma was collected from all patients in the first-in-man study of osimertinib. Patients who were included had acquired EGFR-TKI resistance and evidence of a common EGFR-sensitizing mutation. Genotyping of cell-free plasma DNA was performed by using BEAMing. Plasma genotyping accuracy was assessed by using tumor genotyping from a central laboratory as reference. Objective response rate (ORR) and progression-free survival (PFS) were analyzed in all T790M-positive or T790M-negative patients.ResultsSensitivity of plasma genotyping for detection of T790M was 70%. Of 58 patients with T790M-negative tumors, T790M was detected in plasma of 18 (31%). ORR and median PFS were similar in patients with T790M-positive plasma (ORR, 63%; PFS, 9.7 months) or T790M-positive tumor (ORR, 62%; PFS, 9.7 months) results. Although patients with T790M-negative plasma had overall favorable outcomes (ORR, 46%; median PFS, 8.2 months), tumor genotyping distinguished a subset of patients positive for T790M who had better outcomes (ORR, 69%; PFS, 16.5 months) as well as a subset of patients negative for T790M with poor outcomes (ORR, 25%; PFS, 2.8 months).ConclusionIn this retrospective analysis, patients positive for T790M in plasma have outcomes with osimertinib that are equivalent to patients positive by a tissue-based assay. This study suggests that, upon availability of validated plasma T790M assays, some patients could avoid a tumor biopsy for T790M genotyping. As a result of the 30% false-negative rate of plasma genotyping, those with T790M-negative plasma results still need a tumor biopsy to determine presence or absence of T790M.

Dataset Information

Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.

Aim

Materials & methods

Results

Conclusion

Publications

Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.

Similar Datasets

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