erlotinib

Although the primary endpoint was not met, the combination provided durable control of MPE and was well tolerated, suggesting potential value in symptom-focused management of this high-risk subgroup.

In vitro and in vivo studies demonstrate that pharmacological inhibition of HDAC1 or restoration of TFCP2 acetylation reverses erlotinib resistance in PDAC. These findings unveil a previously unrecognized mechanism of EGFR-TKI resistance and suggest a promising strategy to enhance therapeutic efficacy in PDAC.

In contrast, a distinct set of agents, such as the combination of bevacizumab and erlotinib, is the principal systemic therapy consideration for FH-deficient RCC. Therefore, FH loss by IHC does not necessarily always indicate a pathogenic FH mutation. Further molecular studies are critical in determining the underlying pathogenic mutation.

Treatment with ATP or flunarizine partially attenuated these alterations. (4) Combined ATP and flunarizine administration showed stronger protective effects, improving biochemical parameters and preserving ovarian histology, suggesting a protective role against erlotinib-induced ovarian injury.

The cytotoxicity of the synthesized compounds was evaluated against A-549 and NCI-H460 lung cancer cell lines, as well as normal HEK-293 cells, using erlotinib and doxorubicin as reference standards. A strong association between docking scores and biological activity was noted, validating EGFR as a potential molecular target. The findings designate 8f and 8g as prospective lead compounds for further development as EGFR-targeted anticancer therapies.

In vitro cytotoxicity screening against breast (MCF-7), liver (HepG2), and colon (HCT116) cancer cell lines identified compounds 9, 11, 12, and 13 as the most potent antiproliferative agents, exhibiting activities comparable to or exceeding those of the reference drugs Sorafenib and Erlotinib...Mechanistic investigations revealed that compound 12 exhibited interesting selectivity, with 2.4-fold lower cytotoxicity toward normal MCF10A cells compared to doxorubicin...Additionally, in silico ADME profiling demonstrated good drug-likeness, fulfilling Lipinski, Veber, Egan, and Muegge criteria. Collectively, these findings highlight compound 12 as a promising dual EGFR/VEGFR-2 inhibitor with significant potential for further development as a multitarget anticancer candidate.

Enzyme-binding assays confirmed its potent EGFR inhibitory activity (IC50 = 0.225 μM), comparable to the reference inhibitor erlotinib (IC50 = 0.198 μM)...Molecular simulation studies provide evidence for the preferential binding of 6b to the active state of EGFR, consistent with the experimental results. The synthetic strategy used to prepare the pyrrole-pyrazoline/chalcone scaffold is simple, hence providing efficient access to the title compounds whose potential can be further explored as an EGFR-targeted anticancer chemotype.

P2, N=125, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

Osimertinib treatment is a viable option for patients who progress on frontline first- or second-generation EGFR TKI therapy without rebiopsy and have an unknown T790M mutation status. The RR of 42.7% and median ToT of 5.6 months appear consistent with historical outcomes reported for second-line platinum-based chemotherapy. Osimertinib provides an additional treatment line for patients whose tumors are difficult to access and have an unknown T790M status, making it a valuable treatment option for these patients.

BIOMEDE was a randomized phase 2 trial comparing the efficacy in terms of overall survival (OS) (primary endpoint) of epidermal growth factor receptor (EGFR) inhibitor erlotinib, mTOR inhibitor everolimus and multitargeted tyrosine kinase inhibitor dasatinib in combination with radiotherapy in patients with a biopsy-proven DIPG...A cohort of 66 children with the same inclusion criteria and treated previously with temozolomide-based regimen was used to compare outcome...With comprehensive tumor profiling, BIOMEDE validated prognostic biomarkers as well as informative theranostic biomarkers for future trials. ClinicalTrials.gov: NCT02233049 .

In a clinical trial (ChiCTR2500097714), erlotinib (an EGFR inhibitor) combined with azacitidine plus the HAG regimen, which consists of homoharringtonine, a low dose of cytarabine, and granulocyte colony-stimulating factor priming, achieves a remission rate of 75% in relapsed/refractory AML, likely via MMRN1/EGFR axis blockade. Our findings establish MMRN1 as a dual-functional target for LSC maintenance and immune evasion and propose that disrupting MMRN1 or EGFR remodels the immunosuppressive tumor microenvironment, offering a promising strategy for AML immunotherapy.