ArticleMolecular cancer2025
Promising therapeutic efficacy and safety of a novel integrin α6-targeting peptide-drug conjugate in lung adenocarcinoma.
Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- ANKRD49 promotes immune evasion in lung adenocarcinoma by activating the MEF2A/PD‑L1 axis.Biology direct · 2026Article
- A lactylation-driven prognostic model for lung adenocarcinoma: cellular lactylation heterogeneity and immune insights.Translational lung cancer research · 2025Article
- The immunoregulatory role of integrins in pulmonary diseases.Frontiers in immunology · 2025Review
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Authors and funding
11 authors.
Funding
Abstract
backgroundLung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, with poor prognosis due to rapid tumor growth and resistance to current treatments. Thus, the identification of novel biomarkers and therapeutic strategies has become increasingly important in the management of LUAD.
methodsA novel integrin α6-targeting peptide-drug conjugate, RWYD-MMAE, was designed to increase therapeutic precision and minimize off-target effects. Integrin α6 expression was examined in LUAD tissues and cell lines. The antitumor activity and safety of RWYD-MMAE for LUAD treatment were assessed in vitro and in vivo. Moreover, the combination of RWYD-MMAE with an anti-PD-1 monoclonal antibody was further investigated to elucidate the synergistic therapeutic effects.
resultsIntegrin α6 was overexpressed in LUAD cells and tissues, suggesting that integrin α6 is a promising target of drug action for LUAD patients. RWYD-MMAE exhibited targeted antitumor activity in LUAD cell lines via G2 phase arrest and apoptosis. Notably, the antitumor efficacy of RWYD-MMAE was positively correlated with ITGA6 expression levels. In vivo experiments indicated that RWYD-MMAE significantly suppresses tumor growth with no detectable systemic toxicity. In addition, RWYD-MMAE was able to ameliorate the tumor immunosuppressive microenvironment and sensitized tumors to immunotherapy, thereby achieving a more pronounced therapeutic response when combined with anti-PD-1 immunotherapy.
conclusionThe integrin α6-targeting conjugate RWYD-MMAE demonstrates promising therapeutic efficacy and safety in treating LUAD. The synergistic therapeutic effect of combining RWYD-MMAE with anti-PD-1 immunotherapy provides a new perspective on the potential of combination therapy for LUAD treatment.
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