gefitinib

Patients with epidermal growth factor receptor mutant nonsmall cell lung cancer (NSCLC) often fail to treat gefitinib because of secondary drug resistance...This phenomenon can be utilized to illustrate the drug resistance degrees of PC9GR cells. This study provides diagnostic markers for evaluating the drug resistance of tumors and gives new insight into overcoming the secondary resistance of tumors.

Moreover, FMF-04-159-2, a specific covalent inhibitor of PFTK1, can reverse the effect of PFTK1 on gefitinib resistance in vitro and in vivo. Consequently, these findings shed new light on the mechanism underlying gefitinib resistance, and suggest PFTK1 as a target for gefitinib treatment in NSCLC.

Furthermore, therapeutic drugs, including fluorouracil, afatinib, alpelisib, cedranib, crizotinib, erlotinib, gefitinib, and ipatasertib, were found to induce higher sensitivity in high-risk group. The prognostic signature consisting of four CMRLs displays an outstanding predictive performance and improves the precision of immuno-oncology.

Our study concluded that combination regimens based on third-generation TKIs (osimertinib plus ramucirumab, osimertinib plus chemotherapy, osimertinib plus bevacizumab, amivantamab plus lazertinib and aumolertinib plus apatinib) could be the new and clinically preferable first-line, standard of care for EGFR-mutated advanced non-small cell lung cancer.

Studies have shown that the clinical efficacy of the EGFR tyrosine kinase inhibitor gefitinib alone in treating HCC is limited...Among them, the best complex 6g exhibits significant antiproliferative activity against Huh7 cells and Huh7R (lenvatinib-resistant) cells...In addition, complex 6g causes a significant increase in the accumulation of reactive oxygen species (ROS), disrupts mitochondrial membrane potential (MMP), arrests the cell cycle in the G0/G1 phase, and induces apoptosis. Collectively, our findings demonstrate that complex 6g exhibits potential anti-HCC effects via dual-targeting of EGFR and TrxR.

Combining small-molecule inhibitors targeting MSI2, such as Ro 08-2750, efficiently alleviated chemoresistance in tumor cells exposed to Platinum and Gefitinib. These findings suggest that MSI2 could be a novel therapeutic target for developing strategies to counteract cancer resistance to treatment.

Chemotherapy includes the use of doxorubicin or taxanes generally with platinum-based drugs viz. cisplatin or carboplatin that are administered alone or along with multitarget tyrosine kinase inhibitors viz. Lenvatinib, Sorafenib, Sunitinib, Vandetanib, Pyrazolo-pyrimidine compounds, etc., single target tyrosine kinase inhibitors like Dabrafenib plus Trametinib and Vemurafenib against BRAF, Gefitinib against EGFR, Everolimus against mTOR, vascular disruptors like Fosbretabulin, and immunotherapy with viz. Spartalizumab and Pembrolizumab, are anti-PD-1/PD-L1 molecules...Hence, our review presents a closer view of NDDS as a personalized treatment for TC. We have also discussed the primary challenges facing NDDS in meeting excellence in PM.

Drug sensitivity analysis suggested that Metformin, Gefitinib, and Lapatinib may be more effective in the low-risk group, while Pyrimethamine, Axitinib, and Rapamycin may be more beneficial for high-risk patients. In summary, we identified a 6-gene signature related to dendritic cell dysfunction that can predict prognosis in esophageal cancer, offering valuable insights for personalized therapeutic strategies.

Significant cardiovascular signals were identified for 17 TKIs, including erlotinib, gefitinib, and imatinib...Heatmaps indicated significant signals for drugs such as lapatinib in males and gefitinib in younger patients...These results underscore the importance of individualized risk assessment and management of TKI-treated patients. In conclusion, this study provides valuable insights into the cardiotoxic risk of TKIs, which is essential for developing tailored treatment plans.

We visualized these interactions using Cytoscape to generate individual and combined drug-gene networks, focusing on frequently used drugs such as Erlotinib, Gefitinib, Lapatinib, and Cetuximab...Combined drug networks, such as those for Cetuximab with Lapatinib, Cetuximab with Erlotinib, and Erlotinib with Lapatinib, revealed potential synergies that could enhance therapeutic efficacy by simultaneously influencing multiple genes and pathways. Our findings suggest that a network-based approach to analyzing drug combinations provides valuable insights into the molecular mechanisms of HER2+ breast cancer and offers promising strategies for overcoming drug resistance and improving treatment outcomes.

These findings provide preliminary evidence for the involvement of the CREB3L4/RASEF signaling pathway in LUAD pathogenesis and suggest its potential as a novel biomarker for accurate diagnosis and targeted therapy.

P2, N=0, Withdrawn, Sun Yat-sen University | N=37 --> 0 | Suspended --> Withdrawn

The compounds 7b, 7 h, and 7i produced more potent cytotoxicity than doxorubicin with IC50 values of 1.83 ± 0.1, 2.54 ± 0.14, 2.75 ± 0.15, and 3.63 ± 0.2 μM, respectively...In addition, compound 7b produced a promising multi-kinase inhibition against EGFR (WT) while being very selective toward the mutant forms (L858R and T790M) with IC50 values of 0.099 ± 0.006, 0.064 ± 0.006, and 0.026 ± 0.007 μM, respectively, in comparison to gefitinib and osimertinib...Compound 7b was predicted to have promising oral absorption, good drug-likeness, and low toxicity risks in humans. Moreover, MD simulations confirmed the stable complexes of 7b with EGFRWT, EGFRL858R, and EGFRT790M (with RMSD 0.12-0.35 nm, RMSF 0.2-0.55 nm, SASA 140-150, and Rg 1.80-2.00 nm).

Chemotherapeutic agents such as gefitinib and sorafenib were predicted to be effective against high HJURP-expressing tumors. Its high expression correlates with specific genetic alterations and immune profiles, highlighting its potential as a therapeutic target. Future studies should validate these findings in larger cohorts.

Proteins were precipitated with acetonitrile, and selpercatinib and the internal standard (gefitinib) were separated via HPLC-UV. Thus, this study establishes a simple and sensitive method for quantifying selpercatinib in human plasma. Future studies will analyze plasma samples from patients treated with selpercatinib and utilize this method to explore the relationships among plasma concentration, efficacy, and adverse events to define the therapeutic concentration range.

The ABCG2 rs2231142 polymorphism plays a significant role in the clinical outcomes of patients with EGFR-mutated NSCLC treated with gefitinib, warranting further investigation to clarify its impact on treatment efficacy and patient safety.

Subsequently, Osteoclast differentiation was initiated after Gefitinib was added to the treatment groups...Our findings provide compelling evidence of the essential role of EGFR-related pathways in M1 polarization, osteoclast activation, and ensuing periprosthetic osteolysis. Overall, EGFR presents a novel target for addressing bone resorption-associated conditions triggered by particles or modulated by macrophages and osteoclasts.

A heightened receptivity was noted toward particular chemotherapy drugs, encompassing gemcitabine, vincristine, paclitaxel, gefitinib, and sorafenib, within this high-risk group. Conversely, a superior reaction to cisplatin was distinctly evident among those marked by low MSC scores... The five-gene MSC prognostic model demonstrates substantial efficacy in prognosticating clinical outcomes and gauging responsiveness to chemotherapy and immunotherapy regimens. The genes ZNF165, MXRA7, CEMIP, ARL4C, and CERCAM are underscored as promising candidates warranting further exploration for anti-MSC therapeutic strategies, thereby offering novel insights for personalized treatment approaches in BC.

Inhibition of EGFR restores sensitivity to regorafenib, and the combination of gefitinib and regorafenib demonstrates significant antitumor efficacy both in vivo and in vitro. These findings suggest that this combination could be a potential strategy for patients with advanced HCC.

CD8RGs play an important role in regulating the TME of PAAD. Five hub genes-BCL11A, KLK11, GNG7, PHOSPHO1, and VCAM1-are closely associated with the prognosis of PAAD patients, providing new references for the exploration of biomarkers. Furthermore, our findings offer novel insights for clinical decision-making.

Additionally, these compounds inhibited the migration and invasion of HepG2 cells. One of the compounds was found to be low in toxicity in mice, suggesting its potential as a targeted DNA anti-tumor drug.

Our work develops a novel centrosome-related prognostic signature that accurately predicts OS in LUAD and can assist in clinical diagnosis and treatment.

Moreover, the chimera exhibits significant antitumor efficacy in drug-resistant xenograft mouse models, showcasing improved tissue penetration and low toxicity. This study accentuates the potential of the bispecific EGFR-Met chimera as a promising therapeutic option for NSCLC resistant to EGFR TKIs.

In a xenograft mouse model, SLC34A2 overexpression promoted solid tumor growth and metastasis, while miR-124-3p overexpression inhibited these effects. Our results highlight that the interaction between miR-124-3p and SLC34A2 plays an indispensable role in determining gefitinib resistance in NSCLC cells.

This study aimed to investigate the anticancer mechanisms of deoxybouvardin glucoside (DBG), a glucosidic form of deoxybouvardin from Rubia species, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells...See also the graphical abstract(Fig. 1).

3 TLSGs identified by machine learning and MR can predict the onset, prognosis and clinical treatment of HCC patients, and had significant genetic association with HCC.

This review included 23 randomized clinical trials incorporating 7,006 patients and 11 treatments: erlotinib, gefitinib, icotinib, afatinib, dacomitinib, osimertinib, furmonertinib, aumolertinib, pemetrexed-free chemotherapy (PfCT), pemetrexed-based chemotherapy (PbCT) and placebo. Difference in safety between the third-generation EGFR-TKIs was also first investigated comprehensively. Furthermore, this review elaborated the varied predominate spectrum and ranked the toxicity of EGFR-TKIs for providing toxicity rationale for treatment decisions.

Gefitinib treatment affected NSCLC resistant cells...Both INHBA silencing and X-ray treatment inhibited EMT development. This study demonstrated that INHBA silencing ameliorates EGFR-TKI resistance and enhances the therapeutic effect of radiotherapy in NSCLC.

P=N/A, N=4864, Active, not recruiting, Brigham and Women's Hospital

The nebivolol-gefitinib-loratadine combination may be a promising alternative for lung cancer treatment.

In a corticosteroid immunosuppressed mouse model of invasive pulmonary aspergillosis, inhibition of EGFR with gefitinib decreased whole-lung cytokine and chemokine levels and reduced accumulation of phagocytes in the lung, leading to a decrease in fungal killing, an increase in pulmonary fungal burden, and accelerated mortality...This leads to decreased accumulation of neutrophils and dendritic cells in the lungs, reduced A. fumigatus killing, and increased mortality. These results provide a potential explanation as to why some cancer patients who are treated with EGFR inhibitors develop invasive aspergillosis.

The results of this study demonstrate that the four-drug combination regimen, led by gefitinib, is manageable and tolerated and effective for patients with EGFR-mutated advanced non-squamous NSCLC.

Combination treatment of JHU083 and gefitinib reversed the up-regulation of PD-L1 in bladder cancer cells induced by prolonged glutamine blockade, resulting in the alleviation of T-cell immunosuppression and a significant improvement in therapeutic outcome. These preclinical findings show promise for glutamine metabolism targeting as a viable therapeutic strategy for bladder cancer, with the potential for further enhancement through combined treatment with gefitinib.

The CRCS2 subtype was in a hypoxic state and was characterized by suppression and exclusion of immune function, which was sensitive to gefitinib, erlotinib, and saracatinib. Our findings highlight the key role of CSCs in shaping the ccRCC tumor microenvironment, crucial for therapy research and clinical guidance. Recognizing tumor stemness helps to predict treatment efficacy, recurrence, and drug resistance, informing treatment strategies and enhancing ccRCC patient outcomes.

ARAF amplification was identified in 5-8% of EGFR-TKI-resistant tumors. The possible roles of ARAF in SCLC transformation warrant further investigation.

Collectively, this study revealed the role and mechanism of AREG in negative immune regulation, and targeting AREG might be a novel immunotherapy for LSCC.

Furthermore, CyH inhibited the activation of JAK3/STAT signaling pathway. Taken together, our findings suggest that CyH promotes the sensitivity to gefitinib in NSCLC cells through the inhibition of EGFR activation and PD-L1 expression.

Anticancer efficacy of PPL, erlotinib (ERL), gefitinib (GEF), and cisplatin (CIS) were investigated in H1299 and H1975 cell lines. Treatment with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular level. PPL sensitized lung cancer cells to EGFR-TKI and induced potent cytotoxic effects at low concentrations.

Ultimately, Western blot assays showed BV alone or combined with gefitinib significantly decreased the protein expression of phosphorylated EGFR (p-EGFR) and the protein expression ratio of p-EGFR to EGFR, and increased the protein expression ratio of LC3-II to LC3-I in PC-9 cells or epidermal growth factor-activated PC-9 cells. The results demonstrated that BV could prompt the inhibition of gefitinib on proliferation, migration, and invasion of NSCLC cells via EGFR-mediated autophagy, showing the synergistic anti-NSCLC potential when combined with gefitinib.

We explored the role of ciliated cells in prostate cancer by using Gefitinib and Jasplakinolide compounds to induce ciliated cells in both normal and tumor-like prostate cell lines...Finally, we examined these compounds in 3D cell models, aiming to simulate in vivo conditions. Our study highlights YAP1 as a potential target for novel genetic models to understand the primary cilium's role in mediating resistance to anticancer treatments.

The TKIs used during this period include EGFR inhibitors such as afatinib, erlotinib, gefitinib, and osimertinib and ALK inhibitors such as alectinib and crizotinib. The EGFR-targeted and ALK-targeted therapies appear to have acceptable clinical response rate and safety profile in our population. Close and frequent monitoring of adverse events is advised to ensure a good quality of life and prevent serious complications.

T-BEPRO revealed a particle size of 109.22 ± 0.266 nm with enhanced cellular uptake and activity. Remarkably, parenterally delivered T-BEPRO in tumor-bearing mice showed a substantially higher % tumor growth inhibition (TGI) of 77.6 % with long-lasting tumor inhibitory potential as opposed to individual drugs.