EGFR overexpression

The Herceptin-resistant breast cancer cell line JIMT-1 was used in an in vivo tumor model, and MMTV-erbB2 (Fo5) transgenic mice models were used to evaluate the efficacy and safety of ER121 as neoadjuvant. ER121 is a non-toxic small-molecule erbB kinase inhibitor and holds promise as an oral and systemic therapeutic agent for treating progressive erbB-driven tumors in therapeutic settings. Moreover, ER121 shows potential as a preventive therapy in neoadjuvant settings for erbB2-associated tumors and when administered systemically can dramatically limit erbB2 brain metastases in animal models.

Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.

Lastly, we showcased the targeted BCP-LNPs using a Cetuximab-conjugated formulation...This finding underscores the potential of BCP-LNPs in targeted gene therapy, especially in challenging scenarios such as tumor targeting. Overall, our study establishes the viability of BCP-LNPs as a versatile, efficient, and targeted delivery platform for nucleic acids, opening avenues for advanced therapeutic applications.

Without affecting normal cellular viability, BAI inhibited malignant behavior, interacted with LGR4, and blocked the LGR4-EGFR pathway for brain glioma cells. In conclusion, our data suggested that BAI inhibited brain glioma cell proliferation and induced apoptosis by downregulating the LGR4-EGFR pathway, which provides a novel strategy and potential therapeutic targets to treat brain glioma.

The OLNP@CPT-11 surface was modified with an epidermal growth factor receptor (EGFR) antibody Cetuximab (CET), which can actively target the overexpressed EGFR on the U87 glioblastoma cell surface. Furthermore, magnetic guidance of OLNP-CET@CPT-11 to U87 cells can induce cell death exclusively in the magnetically targeted zone. The dual-targeted strategy also provides the best therapeutic efficacy against subcutaneously implanted U87 tumors in nude mice with intravenously delivered OLNP-CET@CPT-11.

Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer.

P1, N=50, Active, not recruiting, Tavotek Biotherapeutics | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Dec 2025

Knockdown of EGFR expression or pharmacologic stimulation of EGFR endocytosis with EGFR monoclonal antibodies restores T-DXd trafficking and antitumor activity in EGFR-overexpressing cancers in vivo. Our results reveal EGFR overexpression to be a potential mechanism of resistance to T-DXd, which can be overcome by combination therapy strategies targeting EGFR.

Recent molecular data on YA-OCSCC suggests a potential profile characterized by epidermal growth factor receptor overexpression, low tumor mutation burden and an attenuated immune response. Upon confirmation in larger cohorts of YA-OCSCC patients from different geographical areas, the validated markers could aid in selecting tailored treatments.

Chemoresistance is a considerable challenge for gastric cancer (GC), and the combination of cisplatin (DDP) and anti-EGFR therapy failed to show remarkable benefit...Furthermore, EGFR inhibited CYBRD1 via enhancing the miRNA subset and scavenged the redundant ROS to cause DDP resistance. Therefore, to inhibit the miRNA subset at the same time of anti-EGFR therapy might reverse DDP resistance, serving as a potential novel drug for the future treatment of EGFR-overexpressed and DDP-resistant GC.

F5M@mi3/EGFRAfb selectively bound to EGFR-overexpressing MDA-MB-468 cells, visualizing the target cancer cells, while Aldox@mi3/EGFRAfb selectively delivered doxorubicin, leading to target-specific cancer cell death...Subsequent display of EGFRAfb on their surface allowed the visualization of target cancer cells using fluorescent HaloTag ligand labeling and facilitated the killing of target cancer cells by converting the prodrug 5-FC to the cytotoxic drug 5-FU. Modular functionalization of the two distinct spaces in porous SC-mi3 may offer opportunities for developing target-specific functional cargo-delivery nanoplatforms in biomedical fields.

The present study found that sentinel lymph node biopsy was feasible in appropriate patients, and that chemotherapy regimens incorporating anthracycline-class drugs did not appear to improve OS. Anti-angiogenic therapy holds promise as a potentially effective treatment approach for MBC, and the optimization of systemic treatment strategies should be a priority in the management of these patients.

Epidermal growth factor receptor expression was most likely associated with ER and PR negative tumors. Assessments of multiple molecular markers aid to understand the biological behavior of the disease in Ethiopian population. It might also help to predict which group of patients might get more benefit from the selected treatment strategies and which are not.

Silencing these genes inhibited tumor cell functions and enhanced CD8+ T cell activity, both in vitro and in vivo. CLDN1 and EGFR are crucial in PTC, linked to tumor invasiveness, EMT, and immune suppression, presenting them as potential therapeutic targets.

In vivo, streptozocin treatment- and EGFR overexpression-induced growth of xenograft tumors was mitigated once S979 was mutated. Collectively, this work helps comprehend how cells interrogate the nutrient enrichment for proliferation and suggests that although mammalian cell proliferation is controlled by mitogen signaling, the ancient nutrition-sensing mechanism is conserved and still efficacious in the cells of multicellular organisms.

These findings underscore the clinical relevance of EGFR as a prognostic biomarker and therapeutic target, emphasizing the need for further research and the development of targeted therapies to enhance patient outcomes in cancers with EGFR alterations. The co-expression network of EGFR with genes and proteins involved in cell cycle regulation and mitotic control provided insights into the molecular mechanisms of oncogenesis.

EGFR can activate key factors of the PI3K-AKT signaling pathway, AKT and PI3K, and promote their phosphorylation levels. Consequently, we concluded that EGFR interacts with GNB2, facilitating transmembrane signal transduction, activating the PI3K-AKT signaling cascade, controlling cell cycle alterations, stimulating cell proliferation, and promoting tumorigenesis.

Complexes 2 and 2' show promise as dual-function anticancer agents, offering EGFR inhibition, apoptosis induction, and radiosensitization. Their potential as radiopharmaceuticals warrants further in-depth investigation in preclinical models.

The molecular docking results revealed that the key effector components of FZXZP that exerted the above regulatory roles were wogonin and glycitein. All of these results suggest that FZXZP could significantly delay HCC development by inhibiting proliferation and promoting apoptosis of HCC cells, and the EGFR/STAT3 signal axis might be a critical signal axis of FZXZP in suppressing HCC progression.

The binding of 7MeERT and Ertredin to NDUFA12 in glioblastoma was further supported by the inhibition of the oxygen consumption rate. These results suggest that 7MeERT also binds to NDUFA12, inhibits oxidative phosphorylation, and has a higher anti-cancer cell growth inhibitory activity than Ertredin.

We have identified 20, 21 and 23 as potent mutant EGFR inhibitors (≤20 nM), with comparable or better selectivity over WT EGFR, and lower activity at JAK3, than Osimertinib or Rociletinib. Compounds 21 displayed the best combination of EGFR mutant activity, JAK3 selectivity, cellular activity and physicochemical properties. Finally, kinetic studies on 21 were performed, confirming a covalent mechanism of action at EGFR.

This study highlights integrin αvβ6 and EGFR as viable FLI targets in OSCC and LSCC, especially integrin αvβ6 for tumour margin delineation. In PTC, despite lower expressions, the significant overexpression of VEGF-α, c-MET, and EGFR suggests their potential as FLI targets. Our findings support the development of tumour-targeted FLI tracers to improve surgical precision in HNC.

Finally, we demonstrated that in lung adenocarcinoma patients, high expression of AREG and EGFR mutations were mutually exclusive. In conclusion, these data 1) highlight EGFR ligand AREG as a driver of tumor growth in some EGFRWT NSCLC models, 2) illustrate the preclinical efficacy of amivantamab in ligand-driven EGFRWT NSCLC, and 3) identify AREG as a potential predictive biomarker for amivantamab activity in EGFRWT NSCLC.

Similarly, potential immunotherapeutic targets on CSCs, including B7H6, MICA-B, ULBP1, EGFR, and HER2 are overexpressed across cell lines. Targeting these markers may have a preferential role in combating CSCs, an aggressive subpopulation likely consequential to chordoma's high recurrence rate.

We first demonstrated that muscone suppressed TOP2A expression through the EGFR/Integrin β1/FAK pathway, hence restoring anoikis sensitivity in TMZ-resistant GBM cells. These data suggest that muscone may be a promising co-therapeutic agent for enhancing GBM treatment, particularly in cases of TMZ-resistant GBM with elevated TOP2A expression.

Synergistic effects of inhibition of EGFR- and GLUT1-mediated energy metabolism by compound H may present a new strategy for the treatment of TNBC and NPC.

Notably, the inherited length of the CA-SSR I repeat, HERVK9 haploidy, and Exon 7 tetraploidy conferred three times higher odds ratio to survive for more than 10 years under therapy. This may add value in guiding therapies if determined during follow-up in circulating tumor cells or circulating tumor DNA and offers HERVK9 as a potential therapeutic target.

Our data suggested that MET, HER2, and EGFR might be potential therapeutic targets and that their co-expression is a strong prognostic factor for BTCs.

They caused no abnormality in both short- and long-term administrations as well as in healthy mice. In summary, we accomplished significant breakthrough for the therapeutics of intractable lung cancer patients whose cancers become resistant and metastasize.

In this review, we summarize the relationship between EGFR and VEGFR2 signal transduction in promoting cancer growth and how their kinase domain structures can affect the selectivity of an inhibitor as the basis for designing dual inhibitors. In addition, several recent studies on the development of dual EGFR and VEGFR2 inhibitors involving docking simulations were highlighted in this paper to provide some references such as pharmacophore features of inhibitors and key residues for further research, especially in computer-aided drug design.

No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

This proposition was validated in our in vitro and in vivo studies where melatonin synergistically augmented cytotoxicity and apoptosis in Nimotuzumab-treated glioma cells. Thus, melatonin shows promise as a beneficial addition to Nimotuzumab treatment in glioma patients.

No antitumor effect of the EGFR antibody or the photosensitizer conjugate alone was observed in vivo. Our data support evaluating the use of EGFR-IR700-PIT in the management of ES for detecting and eliminating ES cells in surgical margins, and in the treatment of superficial recurrent tumors.

The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV-positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV-negative HNSCC. The detection of circulating tumour tissue-modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV-positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV-positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV-positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice.

In the meantime, tablets containing pure GEF showed only 15 % ± 0.5 release at the same time. The findings of this study offer valuable insights for optimizing the dissolution and hence therapeutic capabilities of GEF while mitigating its limitations.

Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation...Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1...Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.

The GE11-siRNA-CSNPs design, which specifically targets TNBC cells, offers a novel approach for the treatment of breast cancer with improved effectiveness. This study suggests that GE11-siRNA-CSNPs could be a promising candidate for further assessment as an additional strategy in the treatment of TNBC.

P2, N=137, Active, not recruiting, Daiichi Sankyo | Trial completion date: May 2026 --> Dec 2024

Our study demonstrates that EGFR suppression might be an effective alternative treatment option for SEGAs and tubers, as well as other mTOR-associated malformations of cortical development, including FCD2B.

P2, N=137, Active, not recruiting, Daiichi Sankyo | Trial completion date: May 2024 --> May 2026

The western blot analysis also revealed that compound 2d significantly inhibited the overexpression of EGFR in SGC-7901 cells. The study successfully demonstrated the development of N‑pyrazole amino chitosan as a novel class of agent against gastric cancer via inhibition of EGFR.

Thus, the study suggests that EGFR inhibition-mediated sensitization of the aggressive and metastatic breast CSCs in TNBCs toward chemotherapeutics may reduce the relapse of the disease.