BioDrugs最新文献

{"title":"Gene Therapy Strategies for Uveal Melanoma: Adeno-associated Virus Delivery Challenges and Translational Opportunities.","authors":"Rebecca J Wilson, Charmaine A Ramlogan-Steel, William J Deasy, Sarah J Greenstein, Christopher J Layton, Jason C Steel","doi":"10.1007/s40259-026-00794-w","DOIUrl":"10.1007/s40259-026-00794-w","url":null,"abstract":"<p><p>Uveal melanoma is the most common primary intraocular malignancy in adults and remains associated with poor outcomes once metastatic disease develops. Despite advances in local tumour control and molecular prognostication, effective systemic therapies capable of delivering durable benefit are limited. A range of gene-based therapeutic strategies have been explored in uveal melanoma, including immune-based approaches, gene-modified cell therapies and direct gene delivery. While these strategies have yielded important biological insights and modest clinical advances, their broader impact has been constrained by challenges related to delivery, tumour specificity, durability of effect and translational feasibility. This review surveys the current landscape of gene-based therapies investigated in uveal melanoma and synthesises lessons learned from these approaches, with a particular emphasis on the delivery platform as a determinant of therapeutic success. We examine the emerging potential of adeno-associated virus vectors as gene-delivery platforms for uveal melanoma, drawing on their safety profile and capacity for sustained transgene expression. We highlight the need for adaptation beyond native adeno-associated virus serotypes and discuss advances in capsid engineering, targeting strategies and control mechanisms that enable tumour-selective gene delivery. Finally, we consider translational challenges and future directions for integrating targeted adeno-associated virus-based approaches into therapeutic strategies for uveal melanoma.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"801-819"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Home Infusion With Recombinant Human α-Glucosidase in Children With Pompe Disease: The Dutch Experience Over 20 Years Across the Spectrum From Classic Infantile to Late-Onset Phenotypes.","authors":"Imke A M Ditters, Hidde H Huidekoper, Jacqueline F Hardon, Michelle E Kruijshaar, Ans T van der Ploeg, Johanna M P van den Hout","doi":"10.1007/s40259-026-00773-1","DOIUrl":"10.1007/s40259-026-00773-1","url":null,"abstract":"<p><strong>Introduction: </strong>Enzyme replacement therapy (ERT) is the standard treatment for patients with Pompe disease, a hereditary metabolic myopathy. While ERT in the home situation is increasingly common in adults with Pompe disease, experience in children remains limited due to higher dosing requirements and increased risk of infusion-associated reactions (IARs). We analysed the results of the in-hospital and home-based infusion programme applied in the Netherlands to children since 1999 to provide guidance.</p><p><strong>Methods: </strong>We studied hospital and home-based infusions administered to children with Pompe disease (i.e., classic infantile, atypical infantile, and childhood onset phenotypes) who started ERT between 1999 and 2022 and analysed the characteristics of patients and IARs. The IARs were graded by healthcare providers.</p><p><strong>Results: </strong>A total of 11,898 infusions with recombinant human <math><mi>α</mi></math> -glucosidase (rhGAA) were administered in 52 Pompe patients (27 classic infantile, two atypical infantile and 23 childhood onset phenotypes). Of these, 5278 infusions (44.4%) were given in hospital and 6620 (55.6%) were administered at home. IARs occurred in 458 hospital infusions (8.7%) and 110 home infusions (1.7%). The majority of IARs (87.1%) occurred in patients with the classic infantile phenotype. Most IARs were mild; only 21 severe IARs were reported, two of which occurred at home. All IARs could be managed adequately.</p><p><strong>Conclusion: </strong>Recombinant human α-glucosidase can be safely administered at home using our protocol in children with Pompe disease, including those with classic infantile Pompe disease who are more likely to develop IAR, provided that in-hospital treatment has been shown to be safe, and the appropriate infrastructure and clinical support are in place.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"909-923"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetic Comparability of CT-P16 Versus EU-Avastin^® and US-Avastin^® in Healthy Subjects and Patients with Non-Squamous Non-Small Cell Lung Cancer.","authors":"Taekyung Kim, Heungjo Kim, Hongjae Lee, Keumyoung Ahn, Taehong Park, Hyungseok Baek, Min Jung Chang","doi":"10.1007/s40259-026-00800-1","DOIUrl":"10.1007/s40259-026-00800-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;CT-P16 (Vegzelma&lt;sup&gt;®&lt;/sup&gt;) is a bevacizumab biosimilar approved for indications including non-squamous non-small cell lung cancer. We developed an integrated population pharmacokinetic model pooling data from two phase I studies in healthy subjects and one phase III study in patients with non-small cell lung cancer to (i) quantify the influence of the drug product on pharmacokinetic parameters within a single unified framework simultaneously evaluating CT-P16 against both EU-Avastin&lt;sup&gt;®&lt;/sup&gt; and US-Avastin&lt;sup&gt;®&lt;/sup&gt;; (ii) characterise covariate-driven exposure variability, including disease-status effects, across healthy subjects and patients with non-small cell lung cancer, and compare these effects with previously reported analyses of reference bevacizumab and other bevacizumab biosimilars; and (iii) contextualise simulated steady-state exposure under the approved 15 mg/kg every-3-weeks regime against a published exposure-response benchmark, thereby supporting a biosimilar assessment within the streamlined regulatory paradigm.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Concentration data from one phase III trial (NCT03676192) and two phase I trials (NCT03247673; CT-P16 1.2) were pooled. The population pharmacokinetic analysis used nonlinear mixed-effects modelling in NONMEM&lt;sup&gt;®&lt;/sup&gt; (Version 7.4) with first-order conditional estimation with interaction. Drug product (CT-P16, EU-Avastin&lt;sup&gt;®&lt;/sup&gt;, US-Avastin&lt;sup&gt;®&lt;/sup&gt;) and clinical/demographic covariates were evaluated by stepwise selection. Model adequacy was assessed by goodness-of-fit diagnostics, non-parametric bootstrap resampling (1000 replicates), and a visual predictive check. Steady-state exposure under 15 mg/kg every 3 weeks was simulated using both typical population-predicted profiles and the observed phase III patient covariate distribution with inter-individual variability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 8058 serum concentrations from 834 subjects (phase I: 187 healthy male volunteers; phase III: 649 patients with non-small cell lung cancer) were analyzed. A two-compartment model with first-order elimination adequately described the pooled data. Body weight, sex, and disease status were retained as covariates on clearance; sex, baseline serum albumin, and disease status were retained on central volume of distribution. Drug product was not retained as a significant covariate, indicating no clinically meaningful difference between CT-P16 and either EU-Avastin&lt;sup&gt;®&lt;/sup&gt; or US-Avastin&lt;sup&gt;®&lt;/sup&gt;. The estimated body-weight exponent on clearance (0.369) was numerically indistinguishable from previously published values for reference bevacizumab (0.368 [11]) and for the bevacizumab biosimilar PF-06439535 (0.354 [24]). Across covariate-defined subgroups, the median simulated steady-state trough concentrations remained above the published progression-free-survival reference of 89.1 µg/mL.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Wi","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"883-897"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding Patient Access to Advanced Therapies.","authors":"Elena Guillen, Ana Hidalgo-Simon","doi":"10.1007/s40259-026-00797-7","DOIUrl":"10.1007/s40259-026-00797-7","url":null,"abstract":"<p><p>Advanced therapy medicinal products (ATMPs) promise transformative clinical potential, but their use remains limited by complex manufacturing, high prices, and fragmented market access. To explore the existing and potential regulatory pathways to increase access to ATMPs, we conducted a product-level analysis of ATMPs and biologic medicines submitted to the European Medicines Agency up to May 2026, and a review of regulatory pathways and policy frameworks. While certain scientific principles from biologic and biosimilar regulation, such as totality of evidence, fit-for-purpose data, and tailored approaches are transferable, the biosimilar pathway may not be suitable for certain ATMPs. Other approaches, including bio-hybrid applications or prior knowledge-based dossiers, may be better suited to support competitive entry and second-wave innovation. Tailored follow-on pathways, open and well governed platform technologies, and supportive industrial and data sharing policies, are key to facilitate the translation of the scientific promise of ATMPs into sustainable and equitable patient access.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"785-800"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.","authors":"Lourdes Sainero-Alcolado, Dilraj Lama, Mohammad Alzrigat, Marie Arsenian-Henriksson","doi":"10.1007/s40259-026-00798-6","DOIUrl":"10.1007/s40259-026-00798-6","url":null,"abstract":"<p><p>The MYC family oncoproteins, including MYC, MYCN, and MYCL, are potent drivers of tumorigenesis across a broad range of human cancers, frequently linked to aggressive tumor behavior, poor prognosis, and therapy resistance. They function as master transcriptional regulators that orchestrate gene expression programs governing nearly all aspects of tumor development. Despite their pivotal oncogenic role, they have long been considered \"undruggable\" due to their intrinsically disordered structure, lack of enzymatic activity, and the difficulty of targeting their protein-DNA and protein-protein interactions with conventional small-molecule approaches. Recent advances are beginning to overcome these challenges through innovative molecular strategies that either directly inhibit MYC activity or exploit MYC regulatory networks. Importantly, the first direct MYC inhibitor evaluated in humans, OMO-103, recently demonstrated promising antitumor activity in phase I clinical trials. Indirect approaches have focused on suppressing MYC transcription, translation, or stability by targeting upstream signaling pathways, as well as by exploiting MYC-associated cofactor interactions and synthetic lethal vulnerabilities to improve therapeutic specificity. In this review, we highlight the multifaceted roles of MYC in different cancer types and provide a comprehensive overview of current therapeutic strategies targeting MYC with a particular focus on epigenetic modifiers and metabolic vulnerabilities.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"821-867"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why Product Drift Is Not an Issue for Biosimilars/Biologics: Start the Same, Stay the Same.","authors":"Joseph P Park, Hyunhee Oh, Gillian R Woollett","doi":"10.1007/s40259-026-00796-8","DOIUrl":"10.1007/s40259-026-00796-8","url":null,"abstract":"<p><p>Maintaining quality consistently after any manufacturing change is essential for all biologic medicines and is ensured through well-established scientific and regulatory principles. Over nearly 30 years, such manufacturing changes post-approval have been successfully managed and regulated with so-called comparability approaches, and these have become standard regulatory practice globally as ICH Q5E. A robust comparability assessment along with current good manufacturing practices (cGMP)-based regulatory control, maintains consistent product quality over the full lifetime of a product. The occurrence of 'quality drift' (also mislabelled as divergence) reflecting poor manufacturing control has been observed in some rare originator cases but not for biosimilars, nonetheless, highlighting the need for meticulous control. Despite this, hypothetical concerns regarding 'drift' between the originator product and biosimilar products continue to surface and are often portrayed as a unique risk created by biosimilars. This raises an important question: why are biosimilars associated with concerns about drift? Such concerns are unsupported by real-world evidence. Numerous biosimilar products have been maintaining consistent quality over extended periods, in some cases over a decade of use, thereby strengthening confidence in comparability methods and cGMP-based regulatory control. Such confidence then supports approved biosimilars, including interchangeable products, by showing that serial comparability assessments can occur independently for any given biologic. Consistent application of regulatory science to all biologics further demonstrates that good manufacturing control is independent of any specific regulatory pathway or business model.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"777-784"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes After Week-12 Response-Guided Secukinumab Discontinuation in Psoriasis: A Prospective Real-World Cohort Study.","authors":"Xin Ma, Yue Jiang, Dongmei Liu, Quanruo Xu, Fanlingzi Shen, Zhen Duan, Xiangjin Gao, Xiuqi Zhang, Ruiqi Cai, Rui Zhang, Bin Li, Ruiping Wang","doi":"10.1007/s40259-026-00801-0","DOIUrl":"10.1007/s40259-026-00801-0","url":null,"abstract":"<p><strong>Background: </strong>Continuous biologic therapy achieves psoriasis control but may be limited by cost, adherence burden, safety concerns, and patient preference. Evidence on outcomes after early, patient-driven discontinuation of secukinumab in routine practice is limited.</p><p><strong>Objective: </strong>The aim of this study was to describe clinical outcomes after voluntary secukinumab discontinuation among patients achieving predefined week-12 response targets and to explore factors associated with relapse.</p><p><strong>Methods: </strong>This prospective single-center cohort enrolled 172 adults with moderate-to-severe plaque psoriasis initiating secukinumab during 2022-2024. At week 12, patients achieving target response achievement 1 (TRA1: Psoriasis Area and Severity Index [PASI]75, Physician's Global Assessment [PGA] 0/1, or body surface area [BSA] <3%) or nested TRA2 (PASI90, PGA 0/1, or BSA <1%) could discontinue secukinumab under supervision and continue topical therapy. Relapse was defined as loss of PASI75 at weeks 24 or 48.</p><p><strong>Results: </strong>By week 12, 82.6% of patients achieved TRA1 and 66.9% achieved TRA2. Relapse at week 24 and week 48 occurred in 35.9% (51/142) and 45.1% (55/122) of TRA1 patients and in 28.7% (33/115) and 36.7% (36/98) of TRA2 patients, respectively. Week-4 PASI75 responders had lower week-48 relapse rates than non-early responders in TRA1 (29.0 vs 50.5%) and TRA2 (27.6 vs 40.6%). Early response was associated with lower relapse odds in TRA1 at week 48 (adjusted OR 0.33; 95% CI 0.12-0.87). Higher BMI was associated with greater relapse risk, whereas smoking and comorbidities were not independently associated with relapse.</p><p><strong>Conclusions: </strong>In selected patients achieving week-12 response targets and voluntarily discontinuing secukinumab, early response and BMI showed exploratory associations with relapse risk. These findings require validation before informing routine discontinuation decisions.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry (ChiCTR2200066894).</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"925-935"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CD38 Across Autoimmune and Plasma Cell-Driven Immune-Mediated Diseases: Rationale, Clinical Evidence, and Emerging Therapeutic Landscape.","authors":"Dario Roccatello, Savino Sciascia, Daniela Rossi, Roberta Fenoglio","doi":"10.1007/s40259-026-00799-5","DOIUrl":"10.1007/s40259-026-00799-5","url":null,"abstract":"<p><p>Autoimmune diseases remain a major cause of chronic morbidity despite substantial advances in targeted immunomodulatory therapies. In many autoantibody-mediated conditions, disease refractoriness and relapse are driven by long-lived plasma cells, which are largely resistant to conventional immunosuppression and upstream B cell-directed strategies. CD38, a surface molecule highly expressed on plasmablasts and plasma cells and functionally involved in immunometabolic regulation, has emerged as a promising therapeutic target to overcome this limitation. Clinical interest in anti-CD38 therapy has been catalyzed by experience in plasma cell dyscrasias, where anti-CD38 monoclonal antibodies induce rapid and profound depletion of antibody-secreting cells. Over recent years, accumulating reports and early-phase studies have explored the repurposing of CD38-directed therapies in severe, treatment-refractory autoimmune diseases. The most compelling evidence has emerged in lupus nephritis and immune thrombocytopenia, with additional proof-of-concept data in autoimmune cytopenias and plasma cell-driven renal disorders such as immunoglobulin light chain (AL) amyloidosis. These experiences suggest that targeting CD38 can lead to meaningful clinical and immunological improvement, often accompanied by rapid reductions in pathogenic autoantibody production. However, the current evidence base remains heterogeneous and largely derived from small cohorts, case series, and early-phase trials, and important questions remain regarding durability of response, optimal treatment strategies, and long-term safety, particularly with respect to hypogammaglobulinemia and infection risk. We summarize the biological rationale for CD38 targeting in autoimmunity and plasma cell-driven immune-mediated diseases, critically appraise the emerging clinical evidence across disease settings, and discuss key challenges and future directions for integrating plasma cell-directed therapies into immunological disease management.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"763-776"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of Quality Attributes and Analytical Methods Used for Comparative Analytical Assessment of Monoclonal Antibodies as Part of Successful Biosimilar Approvals in the United States and European Union.","authors":"Rakesh Aithal, Olivia M Majedi, Diane McCarthy, Fouad Atouf, Niomi Peckham","doi":"10.1007/s40259-026-00786-w","DOIUrl":"10.1007/s40259-026-00786-w","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) have revolutionized therapeutic treatments by their ability to target specific antigens, leading to enhanced clinical outcomes over other drugs. They are one of the largest modalities within the growing biotherapeutics space and are indicated for a range of diseases. Though transformative, mAbs are still not readily accessible to many patients globally because of their high costs. An increasing number of mAbs are losing patent exclusivity, which has opened the door for the development of biosimilars that could drive down costs and ensure increased access to these life-saving drugs. Regulators approve biosimilars after conducting a rigorous evaluation similar to any other biologic medicine to ensure the safety, quality, and efficacy of these products. To establish biosimilarity, extensive comparative analytical and clinical studies of the biosimilar product with the approved reference product is a regulatory expectation. Growing acceptance from regulators to potentially waive clinical efficacy studies when robust evidence for similarity with reference product is established from analytical, functional, and pharmacokinetic/pharmacodynamic studies will have a major impact on reducing the time and cost of developing biosimilars. Comparative analytical assessment includes side-by-side analysis of the biosimilar with the reference product to demonstrate similarity regarding their physicochemical and functional characteristics. This is usually achieved by identifying product quality attributes (PQAs) that could impact clinical safety and efficacy and applying orthogonal analytical methods to characterize these attributes to identify any differences between the products. This review identifies the common PQAs studied for approved mAb biosimilars in the United States and the European Union through to the end of 2024. We have also compiled the data for the analytical methods used to characterize these attributes and identified a subset of methods universally used among biosimilar applicants. Finally, a brief overview of the risk-based analysis of attributes is summarized from the regulatory submissions.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"713-732"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Giving Antibiotics a Second Chance: Evolutionary Trade-Offs and Phage-Driven Restoration of Antibiotic Susceptibility.","authors":"Michał Wójcicki, Martyna Cieślik, Andrzej Górski, Ewa Jończyk-Matysiak","doi":"10.1007/s40259-026-00789-7","DOIUrl":"10.1007/s40259-026-00789-7","url":null,"abstract":"<p><p>Antimicrobial resistance poses a critical and escalating threat to global public health, driven by the widespread and often unjustified use of antibiotics and the rapid dissemination of resistance determinants. With the antibiotic discovery pipeline largely depleted, alternative and complementary strategies are urgently needed to preserve the effectiveness of existing antimicrobials. Bacteriophages-viruses that specifically infect bacteria-have re-emerged as promising tools not only for direct bacterial eradication but also for reshaping bacterial evolutionary trajectories. This review examines the concept of phage-driven restoration of antibiotic susceptibility, focusing on evolutionary trade-offs that arise when bacteria adapt to phage pressure. Resistance to bacteriophages frequently involves modifications of surface structures, capsules, or efflux systems, changes that often incur fitness costs manifested as reduced virulence, impaired biofilm formation, or increased antibiotic sensitivity. Experimental studies and clinical case reports demonstrate that phage-antibiotic synergy can suppress bacterial growth more effectively than monotherapy, limit resistance emergence, and resensitize multidrug-resistant pathogens to previously ineffective antibiotics. Particular attention is given to mechanisms involving efflux pump targeting, capsule loss, biofilm disruption, and temperate phage-antibiotic interactions. In addition, emerging strategies that combine bacteriophages with CRISPR-Cas systems enable precise targeting and removal of resistance genes, offering a highly selective means to restore antibiotic efficacy and curb horizontal gene transfer. Together, these findings highlight bacteriophages as powerful evolutionary and therapeutic tools capable of giving antibiotics a \"second chance\". Integrating phage-based approaches into antibiotic stewardship frameworks may represent a sustainable path forward in combating multidrug-resistant bacterial infections.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"623-640"},"PeriodicalIF":8.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}