gefitinib

This study highlights CD2AP's critical role in LUAD, particularly in immune microenvironment modulation, metabolic reprogramming, and drug response. CD2AP's high expression is linked to poor prognosis and may serve as a potential target for immunotherapy and drug response prediction.

P3, N=358, Active, not recruiting, Allist Pharmaceuticals, Inc. | Unknown status --> Active, not recruiting | Trial completion date: Jun 2022 --> Mar 2026

In conclusion, this study highlights the significant influence of EGFR activation on EV secretion and cargo composition while demonstrating that EGFR inhibition via gefitinib alters EV-mediated signaling in lung cancer cells. These findings provide insights into tumor behavior, EV-mediated oncogenic communication, and the potential use of EVs as biomarkers and therapeutic targets in NSCLC.

To develop treatment for EGFR-related NSCLC, several tyrosine kinase inhibitors (TKIs) were designed: gefitinib, erlotinib, as first-generation; neratinib, dacomitinib as second-generation; osimertinib, lazertinib as third-generation, as examples. Although structures obtained so far for the EGFR family provide meaningful insights into the mechanisms, the quality and the quantity of the EGFR family structures are insufficient to elucidate the complete structures and functions to overcome NSCLC. This review evaluates the structures of EGFR-HER2 and investigates their relation to NSCLC.

The goal of this study is to fabricate ERLNs for dual delivery of gefitinib (GF) and simvastatin (SV) to PCA cells. Therefore, GFSV-loaded ERLN cargoes are a promising strategy for PCA treatment. In vivo studies are necessary to confirm these findings for clinical applications.

In summary, the results of the current study revealed a promising therapeutic approach for addressing cardiac issues caused by gefitinib treatment in patients with NSCLC. Therefore, quercetin could inhibit the gefitinib‑induced NSCLC‑mediated cardiomyocyte apoptosis via regulating the SHP2/ROS/AMPK/XBP‑1/DJ‑1 signaling pathway through mitochondrial autophagy.

We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Osimertinib is the first choice of treatment with considerable efficacy and safety for EGFR mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively.

Four of the seven drugs (57%) were recommended as highly or moderately preferred treatment options in Japanese guidelines: gemtuzumab ozogamicin for acute myeloid leukemia, gefitinib for EGFR-positive non-small cell lung cancer, bevacizumab for HER2-negative metastatic breast cancer, and atezolizumab with nab-paclitaxel for PD-L1-positive triple-negative breast cancer. Despite regulatory withdrawal in the US due to unproven clinical benefits, drugs retained in Japan received positive guideline recommendations. This finding highlights regional variations in regulatory decisions and different approaches to benefit-risk assessments, suggesting a need for improved transparency in Japan's regulatory decisions and guideline recommendations, with clearer justifications for endorsing drugs that are considered to have unproven clinical benefits in the US.

USP54 upregulation in gefitinib-treated cells was associated with reduced EGFR ubiquitination, stabilizing EGFR and promoting cell survival. These findings suggest USP54 as a critical modulator of EGFR stability and a potential therapeutic target to overcome gefitinib resistance in NSCLC.

The intercalation of cisplatin plus pemetrexed after the response to EGFR-TKI improved PFS but not OS compared with EGFR-TKI monotherapy as the first-line treatment for advanced NSqNSCLC harboring EGFR mutation.

Using Kirsten rat sarcoma viral oncogene homolog (KRASG12S) and B-cell lymphoma 2 (Bcl-2) genes as targets, it is verified that the hairpin DNA oligonucleotides show cytotoxicity only to tumor cells but very low effects on normal cells. In addition, hairpin DNA oligonucleotides designed for KRAS inhibition, which are encapsulated in lipid nanoparticles, inhibit tumor growth in mice and demonstrate excellent antitumor efficacy in combination with gefitinib, but has little effect on normal tissues, suggesting that the proposed strategy enables highly selective tumor therapy and has the potential to give rise to a new class of nucleic acid drugs.

In this study, self-delivery PROTAC nanoparticles (designated as CP NPs) integrating gefitinib-based PROTACs and photosensitizers were developed to efficiently degrade mutated epidermal growth factor receptor (EGFR), a crucial kinase for cell growth and survival, while simultaneously triggering photodynamic therapy and immunotherapy...In a mouse model of lung cancer, primary, distant, and lung metastatic tumors were significantly suppressed. This work highlights the potential of nano-PROTACs for degrading target proteins and facilitating combination photodynamic immunotherapy toward expanding PROTAC applications in cancer therapy.

While third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib, are commonly regarded as first-line therapies, recent studies indicate that crizotinib may offer superior disease control in certain EGFR-mutant patients, particularly those who exhibit poor responses to EGFR TKIs...In patients with EGFR/ROS1 co-mutation, gefitinib is generally effective as a first-line treatment; however, its efficacy can be limited, whereas crizotinib has demonstrated improved disease control. Future research should focus on identifying optimal treatment strategies for patients with EGFR/ROS1 co-mutation to enhance patient outcomes. In conclusion, this case report not only illustrates the effectiveness of crizotinib in managing patients with EGFR/ROS1 co-mutation but also underscores the importance of personalized treatment approaches, offering valuable insights for improving clinical outcomes in NSCLC patients with complex genetic profiles.

In the FLAURA trial, osimertinib demonstrated longer progression-free survival (PFS) and overall survival (OS) compared to gefitinib or erlotinib. However, the clinical impact of dose reduction is not fully understood. Physicians should carefully weigh its benefits and risks before implementation.

Further study indicated that GL inhibited the expression of p53 and p21, thereby upregulated Cyclin D1 expression, thereby alleviating gefitinib-induced cell cycle arrest without impairing its anticancer activity in vivo and in vitro. These findings highlight the potential of GL as a safe adjunct therapy, effectively mitigating gefitinib-induced hepatotoxicity while preserving its anticancer efficacy.

We report the case of a 37-year-old pregnant woman at 19 weeks of gestation who was diagnosed with a stage M1b EFGRmut lung adenocarcinoma, in 2019. After a right upper and middle bilobectomy (T3N1 and R0 pathological status) and a complete cerebellar metastasis resection, she was treated with gefitinib, which offered her a prolonged recurrence-free survival without any negative consequence for the fetal development or the future development of her now 5- year- old child.

In vitro activity assay showed that these compounds can inhibit cell proliferation of HeLa, SKOV3, BGC-823 and HT1080 cells, especially compounds IV and X showed better inhibitory activity on these tumor cells than that of the positive control drug Gefitinib and similar to Vp-16. Mechanistically, selected compound may inhibit the proliferation of SKOV3 cells and trigger apoptosis by activating Sp1 to inhibit Survivin protein expression, which may be promising leading compounds for cancer therapy.

[This retracts the article DOI: 10.3727/096504018X15166204902353.].

Keyword co-occurrence analysis revealed significant research topics including "gefitinib", "chemotherapy", "open label", and "erlotinib." Moreover, keyword burst analysis indicated notable periods of increased research focus on topics such as "osimertinib" and "liquid biopsy", suggesting emerging trends and current hotspots in the treatment of EGFR-mutated NSCLC. This analysis highlights research trends on TKIs for EGFR-mutated NSCLC, emphasizing the importance of targeted therapies like gefitinib and osimertinib for future research and clinical practice enhancement.

Pathological type, liver metastasis, brain metastasis, NSE, and CYFRA 21 - 1 were identified as independent risk factors for stage IV NSCLC patients treated with EGFR-TKIs, while chemotherapy and radiotherapy were determined to be independent protective factors. Taking icotinib or gefitinib, as opposed to osimertinib, was an independent risk factor for advanced NSCLC patients.

However, even with remarkable response rate, progression-free survival (PFS) and survival benefit as compared to the old generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, treatment outcomes for these subsets of patients remain a challenge. Furthermore, in the MARIPOSA phase III randomized study, the combination of the anti-EGFR and anti-MET monoclonal antibody amivantamab combined with the new anti-EGFR TKI lazertinib demonstrated remarkable PFS benefit as compared to single agent osimertinib. This paper will discuss these new treatment options and potential selection criteria for personalized treatment of patients.

This study explores Pluronic® F127 and Soluplus®-based micelles as carriers for Lomustine, Gefitinib, and Docetaxel to determine the optimal system for GBM therapy. In vivo, SM-D significantly reduced tumor mass and cancer cell density, showing a favorable safety profile compared to free Docetaxel, as evidenced by reduced weight loss and histological assessments. Overall, SM-D stands out as the most promising approach for GBM treatment, supporting the potential of nanomedicine in overcoming the barriers to effective glioblastoma therapy.

Analysis such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent accessible surface area (SASA), principal component analysis (PCA), and free energy landscape (FEL) demonstrated that structures of wild EGFR docked with gefitinib are more stable which suggests its susceptibility towards drug than coevolution dependent double mutant. The findings were supported by MM-GBSA binding affinity analysis. The insights from this study highlighted the evolution-induced structural changes which contributes to drug resistance in EGFR and may certainly aid in designing more effective drugs.

Data from 197 patients with EGFR-mutated NSCLC with baseline brain metastasis who received first-line gefitinib, erlotinib or afatinib between May 2013 and January 2020 were retrieved from the Cancer Center database of Chang Gung Memorial Hospital at Linkou for analysis. First- and second-generation EGFR-TKIs were effective for treating previously untreated patients with EGFR-mutated NSCLC with baseline brain metastasis. In conclusion, for patients whose unfavorable factors [a greater number of brain metastases (>3) and LMCs] are associated with worse clinical outcomes, upfront osimertinib therapy, alone or in combination with other therapeutic strategies and procedures, should be considered.

The median ToT in first line (1L) for EGFR+ patients was 11 months for osimertinib (CI: 10.1-NA) and 9 months (CI: 8.2-11.2) for afatinib, dacomitinib, erlotinib and gefitinib. For ALK+ patients, median ToT in 1L was 20 months (CI: 14.7-23.7for alectinib, 11 months (CI: 4.7-NA) for brigatinib, and 7 months (CI: 2.9-21.6) for crizotinib...ToT for targeted therapies was shorter than progression-free survival in clinical trials. However, patients eligible for targeted therapy still had a survival improvement during the study period.

P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Apr 2025 --> Oct 2025

Furthermore, nine candidate drugs with potential therapeutic efficacy in EC were identified: Bleomycin, Cisplatin, Cyclopamine, PLX4720, Erlotinib, Gefitinib, RO.3306, XMD8.85, and WH.4.023. Furthermore, it identifies potential therapeutic agents with efficacy against EC. These findings hold significant promise for enhancing the survival of EC patients and provide valuable insights to inform clinical decision-making in the management of this disease.

Outcomes from routine treatment with erlotinib and gefitinib in New Zealand patients with advanced EGFR-mutant nonsquamous non-small cell lung cancer are comparable with those reported in randomized trials and other health care system-wide retrospective cohort studies. Socioeconomic status, EGFR mutation subtype, and disease extent at cancer diagnosis were independent predictors of treatment outcomes in that setting.

This study clarifies that DKK1 mediates interactions between cancer cells and fibroblasts in gefitinib-resistant lung cancer, contributing to tumor progression. Therefore, we propose DKK1 as a promising anticancer target for the treatment of gefitinib-resistant NSCLC.

P3, N=674, Active, not recruiting, AstraZeneca | Trial completion date: Jan 2025 --> Dec 2025

In this study, we developed NSCLC cells resistant to EGFR-TKI gefitinib and osimertinib and assessed the effect and mechanism of action of ZZC4 on those cells. Further, the proteomic analysis revealed that ZZC4 inhibited HCC827-GR cell growth by upregulating CDKN1B and downregulating CCNA2 and CHEK1. In conclusion, ZZC4 overcomes resistance to gefitinib by altering the cell cycle pathway.

With satisfying prognosis benefits and acceptable brain metastasis rate in long-term follow-up, gefitinib exhibited clinical viability for operable stage II-IIIA EGFR-mutant NSCLC over chemotherapy in the neoadjuvant setting. MPR was significantly associated with both prolonged DFS and OS, manifesting its potential as an essential endpoint for future neoadjuvant trials.

Comprehensive in vitro and in vivo evaluations demonstrated that the synergistic interplay between gefitinib and the CRISPR-dCas9 system significantly enhanced drug sensitivity. The finding underscores the potential of our approach in addressing the issue of lung cancer resistance, offering a promising avenue for personalized and effective cancer therapies.

Moreover, paclitaxel-derived PDTPs show increased sensitivity to EGFR TKI Gefitinib and its combination with paclitaxel selectively induced cell death in Paclitaxel-derived PDTP (PDTP-P) TNBC cells and 3D spheroids by strongly downregulating phosphorylation of EGFR-Src with concomitant downregulation of Lyn and Fyn tyrosine kinases. Collectively, this study identifies a unique hyper-phosphorylation cellular state of TNBC PDTPs established by switching of EGFR-Src family tyrosine kinases, creating a vulnerability to EGFR TKI.

Notably, L1Au2 also induces endoplasmic reticulum stress (ERS) and triggers immunogenic cell death (ICD). In conclusion, this study provides an innovative strategy for overcoming gefitinib resistance in lung cancer by utilizing dual-targeting TrxR-EGFR alkynyl-Au(I) gefitinib derivatives, thereby offering a new approach for treating gefitinib-resistant lung cancer.

Whether first-generation EGFR inhibitors (e.g. icotinib or gefitinib) can sustainably control EGFR-sensitive mutations/C797S NSCLC following third-generation EGFR inhibitor treatment remains insufficiently reported. Our case report discusses a female patient with advanced lung adenocarcinoma carrying an EGFR exon 19 E746_A750delELREA mutation who received almonertinib as first-line treatment and developed C797S resistance during therapy. The patient was subsequently treated with a double dose of icotinib for 8 months until disease progression occurred, along with the development of an EGFR exon 20 T790M point mutation and TP53 mutation. This case provides clinical evidence suggesting that first-generation EGFR-TKIs may be an effective treatment strategy for patients with acquired EGFR 19del/C797S resistance following EGFR TKI therapy.

IGF2BP1/2/3 were found to be highly expressed in LUAD, with high mRNA stability scores (RS) associated with shorter overall survival (OS) and linked to hypoxia, EMT, IL2-STAT5 signaling, immune suppression, and decreased gefitinib sensitivity. In cell-based experiments, siRNA knockdown of IGF2BPs in LUAD cell lines reduced TGF-β signaling pathway-related genes and inhibited cell proliferation. Our findings suggest that the IGF2BPs gene signature is a prognostic biomarker in LUAD, contributing to tumor progression, immune escape, and poor prognosis by activating specific pathways.

Our study uncovered a heightened risk of ILD in NSCLC patients receiving certain EGFR-TKI in conjunction with specific PPIs, as opposed to EGFR-TKI monotherapy. Subsequent analysis indicates that different PPIs may elicit divergent effects on EGFR-TKI-associated ILD, with different EGFR-TKIs exhibiting distinct responses to combinations with different PPIs. Therefore, NSCLC patients undergoing such treatments should be meticulously monitored for ILD.

Longitudinal recurrence risk with chemotherapy did not differ regardless of EGFR mutation status, whereas gefitinib showed a sustained recurrence risk after completion. Meeting Presentation This data was presented at the American Society of Clinical Oncology Annual Meeting 2024 (general poster session, abstract 8023).

In addition, western blot analysis revealed that compound c13 upregulated the Bax/Bcl-2 ratio, and increased the levels of active caspase 3 and PARP1 cleavage, which suggested the involvement of the mitochondrial pathway in compound c13-induced apoptosis. In brief, these results indicated that compound c13 is a promising compound for the treatment of cervical cancer.

Inhibition of the IRE1α-mediated JNK/p38 MAPK pathway further mitigated gefitinib-induced apoptosis and restored MMP. These findings highlight the critical role of ER stress and the IRE1α-JNK/p38 MAPK axis in gefitinib-induced mitochondrial apoptosis, offering potential therapeutic targets for colorectal cancer.

Dacomitinib demonstrated superior survival benefit compared to gefitinib as a first-line treatment in non-small cell lung cancer (NSCLC) patients with common EGFR mutations through ARCHER 1050. The survival benefit of dacomitinib has been demonstrated, indicating its promising efficacy in a real-world setting. The detection rate of the T790M mutation after dacomitinib treatment failure was comparable to that of other second-generation EGFR-TKIs.