Efficacy of nano‐particulated, water‐soluble erlotinib against intracranial metastases of <scp>EGFR</scp>‐mutant lung cancer

Kim, Dong Ha; Choi, Yun Jung; Sung, Kyung Jeh; Yoo, Seung‐Min; Sung, Young Hoon; Kim, Jeong Kon; Choi, Chang‐Min; Yun, Miyong; Lee, Eun Yong; Jin, Yong Suk; Cook, Seungho; Rho, Jin Kyung; Lee, Jae Cheol

doi:10.1002/1878-0261.12394

Cited by 9 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, nowadays, there are advanced novel immunotherapies and targeted therapies that was reported to show increased blood–brain barrier penetration and realize high response rates and more durable control of BM, and advances in radiotherapies and minimally invasive surgical techniques, which are thought to improve the survival outcome of patients with BM 7,17 . For example, EGFR/ALK TKIs had significant intracranial activity and could achieve longer intracranial progression free survival, higher overall response rate than chemotherapy or radiotherapy, which have been proved in many retrospective and prospective studies 18–22 . And some studies have confirmed that stereotactic radiotherapy (SRS) was a well‐tolerated safe option for patients with four or more BM 23–25 .…”

Section: Discussionmentioning

confidence: 94%

Prognostic impacts of extracranial metastasis on non‐small cell lung cancer with brain metastasis: A retrospective study based on surveillance, epidemiology, and end results database

Wang

Zhang

et al. 2020

Cancer Medicine

View full text Add to dashboard Cite

This study was designed to investigate the prognostic value of the number and sites of extracranial metastasis (ECM) in NSCLC patients with BM. NSCLC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were enrolled in analysis. Patients from 2010 to 2013 were included in the training set and those from 2014 to 2015 in the validation set. ECM sites among different subtypes of NSCLC were compared by Chi‐square tests. Kaplan–Meier methods and Cox regression models were performed to analyze survival data. Competing‐risks analysis was used to predict cumulative incidence rates for CSS and non‐CSS cause. We included 5974 patients in the training cohort and 3561 patients in the validation cohort. Most (nearly 80%) NSCLC patients with BM showed 0–1 involved extracranial organ, with the most and least common ECM organ being bone and distant lymph nodes (DLNs) among all subtypes of NSCLC, respectively. The number of involved extracranial organs was an independent prognostic factor for patients with BM from NSCLC ( p < 0.001). Patients with 0–1 ECM had better survival than those with larger number of involved extracranial organs ( p < 0.001). Cumulative incidence rates for CSS were increased with the number of ECM raising ( p < 0.001). All involved extracranial organs were associated with worse survival ( p < 0.05). In patients with single‐organ ECM, we observed a better prognosis in lung and bone metastasis, while liver metastasis showed worst survival. But the difference in survival in these patient groups was relatively small. Patients with liver metastasis had higher cumulative incidence rates for CSS than that in patients with lung and bone metastasis ( p < 0.05). More extracranial metastases were associated with poor prognosis in NSCLC patients with BM and ECM sites showed limited effect on survival. Tailored treatments would be reasonable for BM patients from NSCLC with different metastasis patterns.

show abstract

Section: Discussionmentioning

confidence: 94%

Prognostic impacts of extracranial metastasis on non‐small cell lung cancer with brain metastasis: A retrospective study based on surveillance, epidemiology, and end results database

Wang

Zhang

et al. 2020

Cancer Medicine

View full text Add to dashboard Cite

show abstract

“…synthesized water-soluble erlotinib (NUFS-sErt) by using a nano-particulation platform technology utilizing fat and supercritical fluid (NUFS™) to resolve the low solubility problem that typically prevents the creation of injectable forms of EGFR-TKIs. The effects of NUFS-sErt were similar to those of conventional erlotinib in terms of inhibiting the proliferation of EGFR-mutant lung cancer cells and suppressing EGFR signaling ( 90 ). By prolonging circulation time, improving drug solubility, and overcoming drug resistance, Nanotechnology-based targeted therapy has shown great promise for the treatment of advanced lung cancer.…”

Section: Nanotechnology-based Therapeutics For Lung Cancermentioning

confidence: 88%

Advanced diagnostic and therapeutic strategies in nanotechnology for lung cancer

et al. 2022

View full text Add to dashboard Cite

As a highly invasive thoracic malignancy with increasing prevalence, lung cancer is also the most lethal cancer worldwide due to the failure of effective early detection and the limitations of conventional therapeutic strategies for advanced-stage patients. Over the past few decades, nanotechnology has emerged as an important technique to obtain desired features by modifying and manipulating different objects on a molecular level and gained a lot of attention in many fields of medical applications. Studies have shown that in lung cancer, nanotechnology may be more effective and specific than traditional methods for detecting extracellular cancer biomarkers and cancer cells in vitro, as well as imaging cancer in vivo; Nanoscale drug delivery systems have developed rapidly to overcome various forms of multi-drug resistance and reduce detrimental side effects to normal tissues by targeting cancerous tissue precisely. There is no doubt that nanotechnology has the potential to enhance healthcare systems by simplifying and improving cancer diagnostics and treatment. Throughout this review, we summarize and highlight recent developments in nanotechnology applications for lung cancer in diagnosis and therapy. Moreover, the prospects and challenges in the translation of nanotechnology-based diagnostic and therapeutic methods into clinical applications are also discussed.

show abstract

“…Based on these findings, a phase II/III clinical trial to evaluate this strategy in patients with recurrent GBM (NCT03025893) is ongoing with sunitinib dosing of 700 mg once every 2 weeks. Alternative approaches such as intrathecal TKI injection may also be considered to optimize local exposure, but this has been studied only in a preclinical model with nano-particulated, water-soluble erlotinib (39). Besides achieved drug concentrations at the target site, the signaling context or network in tumors is essential for TKI efficacy as well (40,41).…”

Section: Discussionmentioning

confidence: 99%

Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma

Linde

Labots

Brahm

et al. 2022

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Tyrosine kinase inhibitors (TKI) have poor efficacy in patients with glioblastoma (GBM). Here, we studied whether this is predominantly due to restricted blood–brain barrier penetration or more to biological characteristics of GBM. Patients and Methods: Tumor drug concentrations of the TKI sunitinib after 2 weeks of preoperative treatment was determined in 5 patients with GBM and compared with its in vitro inhibitory concentration (IC50) in GBM cell lines. In addition, phosphotyrosine (pTyr)-directed mass spectrometry (MS)-based proteomics was performed to evaluate sunitinib-treated versus control GBM tumors. Results: The median tumor sunitinib concentration of 1.9 μmol/L (range 1.0–3.4) was 10-fold higher than in concurrent plasma, but three times lower than sunitinib IC50s in GBM cell lines (median 5.4 μmol/L, 3.0–8.5; P = 0.01). pTyr-phosphoproteomic profiles of tumor samples from 4 sunitinib-treated versus 7 control patients revealed 108 significantly up- and 23 downregulated (P < 0.05) phosphopeptides for sunitinib treatment, resulting in an EGFR-centered signaling network. Outlier analysis of kinase activities as a potential strategy to identify drug targets in individual tumors identified nine kinases, including MAPK10 and INSR/IGF1R. Conclusions: Achieved tumor sunitinib concentrations in patients with GBM are higher than in plasma, but lower than reported for other tumor types and insufficient to significantly inhibit tumor cell growth in vitro. Therefore, alternative TKI dosing to increase intratumoral sunitinib concentrations might improve clinical benefit for patients with GBM. In parallel, a complex profile of kinase activity in GBM was found, supporting the potential of (phospho)proteomic analysis for the identification of targets for (combination) treatment.

show abstract

Efficacy of nano‐particulated, water‐soluble erlotinib against intracranial metastases of EGFR‐mutant lung cancer

Cited by 9 publications

References 15 publications

Prognostic impacts of extracranial metastasis on non‐small cell lung cancer with brain metastasis: A retrospective study based on surveillance, epidemiology, and end results database

Prognostic impacts of extracranial metastasis on non‐small cell lung cancer with brain metastasis: A retrospective study based on surveillance, epidemiology, and end results database

Advanced diagnostic and therapeutic strategies in nanotechnology for lung cancer

Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma

Contact Info

Product

Resources

About