erlotinib

4-anilinoquinazoline scaffold, a key structure in the development of EGFR-TKI anticancer drugs such as Gefitinib and Erlotinib, continues to drive advancements in non-small cell lung cancer (NSCLC) therapy. Mechanistic studies revealed that B10 inhibited the AKT/GSK-3β/β-catenin signaling pathway, downregulating Wnt target genes (c-Myc, c-Jun), and reduced COX2 expression and IL-8 levels, showcasing its dual anti-inflammatory and antitumor effects. These results position B10 as a promising NSCLC therapeutic candidate, combining potent efficacy with a favorable safety profile, and enhance our understanding of the SAR and mechanism of action of 4-anilinoquinazoline derivatives.

The observed interactions with JAK2 and JAK3 suggest a potential mechanism for Melittin's activity. These results highlight the potential of Melittin as a promising adjuvant to Erlotinib for the treatment of NSCLC.

P1/2, N=104, Recruiting, UNC Lineberger Comprehensive Cancer Center | Not yet recruiting --> Recruiting

Patients with KL expression subtype tumors may derive better OS and PFS from abemaciclib versus erlotinib in KRAS-mutated non-small cell lung cancer. These results should be further validated in an independent dataset.

P2, N=125, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

The cellular inhibitory effects of single and co-treatment of CB538 with EGFR-TKIs were evaluated in the established EGFR-TKI-resistant cells [PC9/ER (erlotinib resistance), HCC827/OR (osimertinib resistance)]. Additional treatment with CB538 enhanced sensitivity to EGFR-TKIs in two EGFR-TKI-resistant NSCLC cells by inhibiting EGFR/MET/Axl pathway axis. Overall, the treatment effects of CB538 were confirmed to relieve EGFR-TKI-driven resistance in EGFR-mutant NSCLC cells.

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 drug specifically targets human breast cancer cell lines (MCF-7) that overexpress the epidermal growth factor receptor (EGFR). The confocal luminescence microscopic photographs exhibit sufficient luminescence staining in MCF-7 cells.

Erlotinib and Doxorubicin served as the reference drugs. To further validate these findings, docking simulations of the promising derivatives 7i and 7f were conducted to assess their anticipated binding affinities with EGFR and its T790M/L858R mutants. Thus, compound 7f has the potential to be developed into a potent anticancer agent.

In addition, by slightly raising the temperature of TC‑HT, TC‑HT treatment alone produced antineoplastic effects without damaging the normal IMR‑90 lung cells. The method presented in this study may be applicable to other combination therapies and could potentially act as a starter for anticancer treatments, with fewer side effects.

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.

P=N/A, N=80, Completed, Liaocheng People's Hospital; Liaocheng People's Hospital

P=N/A, N=51, Not yet recruiting, The second affiliated hospital of the army medical university; The second affiliated hospital of the army medical university

UBE2K facilitated the erlotinib resistance and induced EMT in OSCs via regulating the mTOR signaling.

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.

The lowest levels of amino acids and polyamines like serine, threonine, spermine, and spermidine were obtained at 72 hours with erlotinib encapsulated in poly(lactide-co-glycolide) (PLGA) nanoparticles, showing that the drug resistance may in part be overcome with this nanoparticles. The encapsulation of erlotinib with PLGA showed effects and influenced critical metabolic pathways, especially pointing out the need to lower drug resistance and signifying it's potential use as an effective treatment strategy for NSCLC.

The mRNA expression of YWHAG was upregulated in LUAD and could serve as a potential predictive biomarker for prognosis and therapeutic efficacy, particularly in response to cisplatin, paclitaxel, docetaxel, and erlotinib. In conclusion, our findings suggest that YWHAG could serve as an attractive prognostic biomarker and a potential marker for drug response. Moreover, our study highlights that YWHAG exerts its oncogenic function through the JAK2/STAT3 signaling pathway, offering new insights into potential therapeutic strategies for LUAD.

Drug sensitivity analysis showed high-risk patients were more responsive to Navitoclax as well as Rapamycin, but low-risk ones were more sensitive to Afatinib and Erlotinib, highlighting the model's usefulness in guiding personalized treatment. This research emphasizes the crucial role of glycolysis in ESCC progression a well as immune modulation, offering a novel glycolysis-related risk score model with significant prognostic and therapeutic implications. These findings provide a basis for risk-based stratification and tailored therapeutic strategies, advancing precision medicine in ESCC.

P=N/A, N=8300, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

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.

After several subsequent lines of treatment including erlotinib and carboplatin+pemetrexed+osimertinib, repeat genetic sequencing identified a HER2 exon 20 insertion (A775_G776insYVMA) in both blood and tissue. This report represents the first published case detailing the safety and efficacy of a combination fam-trastuzumab-deruxtecan and osimertinib in a patient with NSCLC and HER2-mutated resistance after EGFR-targeted therapy. The findings from this report suggest that fam-trastuzumab-deruxtecan can be safely given in combination with osimertinib and should be considered as subsequent-line therapy for patients who progress on osimertinib and develop a HER2 resistance mutation.

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.

Thus, intermittent low-dose ERL + SUL treatment enhances tumor-associated MHC expression and remodels the immune cell niche toward a more permissive "helper" immune microenvironment. We conclude that early immune-interception strategies targeting interferon-γ signaling may benefit FAP patients at drug doses below the clinical standard of care.

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.

P1, N=55, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

Compound 4e exhibited the highest inhibitory activities, with IC50 values of 0.055 ± 0.002 μM for EGFR and 0.068 ± 0.003 μM for BRAFV600E, compared to the reference drugs erlotinib (IC50 0.06 ± 0.002 μM) and vemurafenib (IC50 0.035 ± 0.001 μM), respectively. Docking simulations were employed to analyze the modes and scores of compounds 4d-g with respect to EGFR and BRAFV600E. The results revealed that compound 4e exhibited strong affinity for both EGFR and BRAFV600E compared to the reference drugs with values of - 3.226 and - 3.474 kcal/mol, respectively.

P1/2, N=33, Terminated, Spanish Lung Cancer Group | N=50 --> 33

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.

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.

High-risk group showed low immune cell infiltration, high TIDE score, and worse prognosis, and the patients in this group exhibited a high drug sensitivity to Cisplatin, Erlotinib, Paclitaxel, Saracatini, and CGP_082996. GJB3, DKK1, CPA3, and KRT6A were all high- expressed in LUAD cells, and silencing GJB3 inhibited the migration and invasion of LUAD cells. A novel NMRG signature was developed, contributing to the prognostic evaluation and personalized treatment for LUAD patients.

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.

According to the mechanistic study, the most potent compounds (9a, 9b, 10e, 10f, & 10i) displayed remarkable inhibitory effectiveness against EGFR and BRAFV600E and were more potent than reference drugs erlotinib and vemurafenib. Molecular docking study for compounds 9a, 9b, 10e, 10f, and 10i agreed with mechanistic results.

P1, N=237, Active, not recruiting, AbbVie | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

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

Compound 8c, which contains a methoxy group on the benzenesulfonamide tail, exhibited notable EGFR inhibitory activity (IC50 = 0.161 µM), similar to that of Erlotinib (IC50 = 0.142 µM)...In-vivo, compound 8c demonstrated comparable and/or superior efficacy compared to doxorubicin in decreasing tumor volume, weight, TNF-alpha, and COX-2 levels in the SEC model, alongside improved histopathological and immunohistochemical results...Pharmacokinetic and toxicity evaluations indicated that compound 8c exhibits favorable drug-like properties and a safer toxicity profile. These findings identify compound 8c as a potential candidate for the development of safe and effective anti-cancer therapies, necessitating additional preclinical investigations.

VEGF/EGFR directed treatment regimes, such as Erlotinib/Bevacizumab demonstrate efficacy against HLRCC-associated RCC [6]. Changes made in the recent 2022 WHO classification impact the diagnosis of HLRCC in multiple ways. This commentary aims to point out this impact and to raise awareness among pathologists as well as clinicians involved in the care of patients with HLRCC.

We tracked the phylogenetic history of an EGFR mutant lung cancer treated with erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine (NPV) targeting ten somatic mutations, including EGFR exon 19 deletion (ex19del). Data from the TRACERx 421 cohort3 provide evidence that pre-WGD mutations better represent clonal variants, and owing to their presence at multiple copy numbers, are less likely to be lost in metastatic transition. These data highlight the power of phylogenetic disease tracking and functional T cell profiling to understand mechanisms of immune escape during combination therapies.

The two derivatives halted the cell cycle progression of treated cancer cells and induced apoptosis as affirmed by flow cytometry along with RT-PCR-determined overexpression of the pro-apoptotic genes p53, Caspase 3, and Bax. Notably, docking and molecular dynamics simulations of members of this series of quinazolin-4-one derivatives showed that analogs with a short linker at the N3 position of the quinazoline ring exemplified by 5f bind to the active form of EGFR with their terminal aryl ring dwelling in the BPI pocket similar to erlotinib, while those with a longer linker represented by 15a bind to the inactive form in a comparable manner to lapatinib lodging the terminal phenyl in the BPII pocket.

P1, N=498, Recruiting, Genentech, Inc. | Trial primary completion date: Mar 2025 --> Feb 2026

Based on bioinformatics analysis, we discovered a new classification method based on IFN-γ genes, which could divide thyroid cancer patients into three populations with significant characteristics. Different populations had different mutation patterns, immune infiltration levels, and candidate therapeutic drugs.

P1/2, N=44, Recruiting, The University of Texas Health Science Center at San Antonio | Not yet recruiting --> Recruiting

Erlotinib (ERL) is a first-line targeted therapy for patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC)...Upon endocytosis and interaction with overexpressed GSH in A549 cells, the disulfide-bond linker is cleaved to release three components: ERL, UA (which downregulates β-catenin/TCF4/CT45A2 signaling pathways, inducing apoptosis in ERL-resistant L858R/T790M mutant cells-a key factor in acquired resistance to ERL treatment), and QM-OH. Hence, this work provides a universal model for multifunctional NSCLC therapy that effectively addresses ERL resistance while enhancing cytotoxicity and biocompatibility.