gefitinib

In patients with EGFR-mutant lung adenocarcinoma receiving gefitinib or other EGFR-TKIs, the development of new pulmonary nodules should not be hastily attributed to disease progression; secondary pulmonary cryptococcosis should be considered in the differential diagnosis.

P1/2, N=108, Completed, Sunshine Lake Pharma Co., Ltd. | Active, not recruiting --> Completed | N=158 --> 108

This study identifies/validates key mechanisms of EGFR-TKI resistance and suggests combinatorial therapeutic strategies as potential interventions against EGFR-TKI-resistant lung cancers, with promising implications for improving clinical outcomes.

Hedyotis diffusa can modulate the IGF-1R/PI3K/AKT-EMT pathway by targeting Akt, EGFR, and other key proteins, thereby intervening in acquired resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma.

Importantly, the inhibitory effects of PRDX1 knockdown on ccRCC could be attenuated by EGF activation in vitro, as well as the oncogenic functions enhanced by increasing PRDX1 was blocked by gefitinib, a specific inhibitor of EGFR. Treatment with PRDX1 inhibitor showed that PRDX1 inhibition restrain the growth and metastasis of ccRCC. In summary, the findings of this study revealed a novel role of PRDX1 in triggering ccRCC progression by inducing the phosphorylation of EGFR, supporting that PRDX1 may serve as a potential therapeutic target for the clinical management of ccRCC.

TOPK also contributes to resistance to anti-cancer agents such as doxorubicin, gefitinib, oxaliplatin, and sorafenib through its influence on activator protein-1, phosphatase and tensin homolog, sirtuin 1 (SIRT1), p53, and additional downstream effectors. Although numerous natural and synthetic inhibitors of TOPK have been identified, their clinical application remains at an early stage. Overall, current evidence presents TOPK as a promising biomarker and therapeutic target with broad relevance across diverse cancer types.

Finally, the suppression of epidermal growth factor receptor (EGFR) activation by gefitinib resulted in the inhibition of the SRC/STAT3/HK2 axis...HK2 promotes stemness mainly through non-metabolic means, not broad metabolic shifts. Targeting this pathway could overcome radioresistance and enhance TNBC outcomes.

Critically, the STING inhibitor H-151 abolished CEP's antitumor effects in vitro. Our findings reveal a novel dual mechanism action of CEP and nominate it as a potential candidate for overcoming TKI resistance in NSCLC.

Notably, these derivatives successfully suppressed oncogenic activation and colony formation even in gefitinib-resistant NSCLC models. Collectively, this study identifies sulfonamide-modified butein derivatives, particularly 8o (MRC-B-016) and 8p (MRC-B-018), as promising dual-targeting agents. Future research will focus on expanding the structure-activity relationship and conducting comprehensive in vivo evaluations to advance these chemotypes toward clinical translation for treatment-resistant lung cancer.

High TRPRS was associated with diminished cytotoxic T-cell infiltration and predicted resistance to multiple therapeutics-including cisplatin, carmustine, gefitinib, buparlisib, and afatinib. Functional assays demonstrated that IFNGR2 knockdown suppressed glioma cell proliferation and attenuated NF-κB signaling, underscoring its role as a key driver within the TRP network. TRPRS provides a robust, biologically grounded tool for simultaneous prognostication and therapy guidance in GBM, highlighting TRP signaling as a therapeutic vulnerability.

Mechanistically, galangin suppressed M2 macrophage polarization, directly interacted with the efferocytosis-related targets CAMK2A and MERTK, and reduced their expression. Together, these findings establish efferocytosis as a novel and targetable vulnerability in drug-resistant NSCLC and highlight galangin as a promising sensitizer for overcoming resistance to two major targeted therapies.

Gefitinib and osimertinib, the first-generation and third-generation EGFR-TKI, have shown promising results in patients with EGFR-mutated lung cancer in clinical treatment. Moreover, PDK1 inhibitor JX06 rendered cancer cells more sensitive to gefitinib treatment in vivo, and JX06 and gefitinib combination treatments have a synergic effect to inhibit tumor growth. In conclusion, the KDM3A/METTL16/PDK1 axis plays an important role in cancer development and TKI resistance, which may offer new prognostic biomarkers and therapeutic targets for TKI resistance in the future.