The study suggests that hybrid scaffolds combining key pharmacophoric features from Osimertinib and Brigatinib along with Lys745 targeting warheads, could enhance selectivity and potency. Fourth-generation TKIs targeting Lys745 offer a novel therapeutic avenue, potentially overcoming mutation-induced resistance and improving NSCLC treatment outcomes. This approach represents a critical advancement toward durable clinical responses in patients with drug-resistant cancer.

This prodrug demonstrates superior safety compared to natural DON and greater antitumor activity against resistant tumors compared to the clinical phase II drug DRP104. These findings may address the clinical limitations of GLS1 allosteric inhibitors and underscore prodrug strategies in effectively treating Osimertinib-resistant lung cancer, providing a foundation for future clinical trials.

The patient, now on combination therapy for exceeding 12 months, exhibits further decreased tumor size and a high quality of life. This case underscores the importance of precise molecular diagnosis in guiding therapeutic strategies and provides a valuable reference for clinical decision-making in EGFR-positive NSCLC cases with atypical mutations.

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.

Notably, the half-maximal inhibitory concentration (IC50) of commonly used chemotherapeutic drugs, such as lapatinib and mitomycin, was inversely associated with TRAF3IP3 expression in HCC patients. TRAF3IP3 may be as a novel and promising biomarker for prognosis prediction and immunological evaluation of HCC.

Furthermore, furmonertinib caused similar changes in apixaban pharmacokinetics. The pharmacokinetic results suggest that it is essential to alert the effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban in clinical practice.

P1, N=14, Recruiting, University of Alabama at Birmingham | Trial primary completion date: Mar 2025 --> Mar 2026

P3, N=516, Recruiting, Shanghai JMT-Bio Inc.

Many patients require osimertinib dose reduction due to adverse events, but this process does not adversely affect the drug efficacy.

We further discussed the factors determining the efficacy of ICIs in EGFR-mutated NSCLC patients, the mutation subtypes and microenvironment characteristics of potential responders. More importantly, we provided insights into areas worth further investigation in the future.

We found that immunotherapy and EGFR inhibitor combination therapy showed promise in treating patients with HNSCC and exhibited safety with acceptable adverse events. This review may provide valuable insights for the future development of treatments and formulation of therapeutic strategies for HNSCC, as well as useful information for the future design of clinical trials.

The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is widely used as a first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC). In three cases of EGFR-L858R+V834L, other co-mutations, including TP53, CTNNB1, and RB1, were detected either before or after afatinib resistance. These results suggested that V834L cooperates with other coexisting mutations to influence the therapeutic efficacy of EGFR-TKIs.

P2, N=33, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Oct 2024 --> Apr 2025

P2, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jul 2025 --> Oct 2025

P1, N=25, Completed, Dizal Pharmaceuticals | Recruiting --> Completed | Trial primary completion date: Aug 2024 --> May 2024

Compound 31 inhibited EGFR L858R/T790M/C797S in biochemical assays with a Ki = 2.1 nM and EGFR del19/T790M/C797S in a Ba/F3 cellular assay with an IC50 = 56.9 nM. The deuterated analogue of 31 (38) demonstrated dose-dependent tumor growth inhibition in a Ba/F3 EGFR del19/T790M/C797S CDX model by 47% at 50 mg/kg BID and 92% at 100 mg/kg BID.

The constructed prognostic model showed promise in predicting the survival of LUAD patients. Notably, KCTD12 and CCT6A might be candidate biomarkers for improving diagnostic performance and guiding individualized therapy for EGFR-TKI-resistant LUAD patients.

This study provides crucial insights into therapy guidance for EGFR-mutated NSCLC patients with MRD, potentially enhancing patient outcomes.

P2, N=28, Not yet recruiting, Shanghai Zhongshan Hospital

P1, N=51, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: Jan 2025 --> Jun 2025

P2, N=70, Recruiting, Li-kun Chen

This activation culminates in the expression of genes associated with the differentiation of the AML cells into DCs as well as pyroptosis, effectively reshaping the immune microenvironment both in vitro and in vivo. Overall, this study marks the first instance of a gold-based small molecule inducing the direct differentiation of tumor cells into immune cells and offers a promising and innovative strategy for the design of AML immunotherapies.

Third-generation TKIs, such as osimertinib, almonertinib and furmonertinib, are effective for the treatment of NSCLC that is EGFR-sensitizing mutation-positive and T790M-positive. To the best of our knowledge, the present report describes the first case of a patient with lung adenocarcinoma who had multiple co-existing EGFR resistance mutations, including EGFR L718Q, EGFR C797S, EGFR C797G, EGFR L792H, EGFR V802F and EGFR V689L. These mutations conferred resistance to almonertinib, whilst maintaining sensitivity to afatinib.

P2, N=0, Withdrawn, Sun Yat-sen University | N=85 --> 0 | Recruiting --> Withdrawn

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

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

P3, N=1000, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting | Trial completion date: Jan 2032 --> Dec 2032

P2, N=46, Recruiting, Institut de cancérologie Strasbourg Europe

Finally, it was demonstrated that erlotinib treatment alleviated carvacrol-induced dermatitis. These data demonstrate that erlotinib ameliorates skin inflammation by regulating Akt and NF-κB-mediated keratinocyte proinflammation, suggesting the therapeutic potential of erlotinib, a clinically used EGFR inhibitor, in skin inflammatory diseases.

An osimertinib and ICI-induced irAE mouse model was constructed that showed osimertinib combined with ICIs inhibited EGFR phosphorylation and activated the IL-6/JAK/STAT3 signaling pathway in mouse liver macrophages, which led to the release of relevant cytokines.

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.

P2, N=57, Recruiting, Zhejiang Provincial People's Hospital

Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group...Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.

No abstract available

No abstract available

Afatinib is a viable treatment option for tissue or ctDNA-detected EGFR mutant NSCLC comorbid patients, with a proportion achieving long-term clinical benefit. Plasma ctDNA testing improved EGFR mutant identification and its clearance predicted improved PFS and OS.

Collectively, our results indicate that afatinib induces intestinal epithelial barrier dysfunction via mechanisms involving NF-κB-iNOS-MLCK pathways. This finding may pave the way for developing therapeutic strategies to reduce adverse effects and enhance efficacy of TKI in cancer patients.

P1, N=128, Not yet recruiting, Kumquat Biosciences Inc.

BRAF class 3 mutations in NSCLC may identify a novel targetable population sensitive to EGFR-TKIs.

In this cohort study of patients with EGFR-mutant NSCLC, osimertinib was associated with a higher incidence of CTRCEs compared with other EGFR TKIs; CTRCEs were independently associated with overall survival. These findings highlight the need for ongoing cardiac monitoring in these patients, regardless of preexisting cardiac risk factors.

P1/2, N=74, Not yet recruiting, Fudan University