{"title":"Allogeneic double-negative T-cell therapy for acute myeloid leukemia","authors":"Enoch Tin , Jongbok Lee , Li Zhang","doi":"10.1016/j.coph.2025.102537","DOIUrl":"10.1016/j.coph.2025.102537","url":null,"abstract":"<div><div>CD3<sup>+</sup>CD4<sup>−</sup>CD8<sup>−</sup> double-negative T cells (DNTs) represent a unique subset of T lymphocytes with potent cytotoxicity against acute myeloid leukemia (AML). Importantly, allogeneic DNTs do not induce graft-versus-host disease and have demonstrated characteristics suitable for off-the-shelf cellular therapy with promising efficacy in early-stage clinical trials. DNT therapy can synergize with conventional AML treatments and can be transduced with chimeric antigen receptors (CARs). Notably, persistent CAR<sup>+</sup> T cells in patients, who achieved long-term remission, predominantly have a DNT phenotype. The unique and versatile therapeutic properties of allogeneic DNTs position them as a strong candidate among adoptive cellular therapies for AML.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102537"},"PeriodicalIF":4.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colloidal drug delivery systems for infectious diseases of skin","authors":"Sopan Nangare , Varda Joshi , Shrikant Magdum , Riya Patil , Vishin Patil","doi":"10.1016/j.coph.2025.102536","DOIUrl":"10.1016/j.coph.2025.102536","url":null,"abstract":"<div><div>Infectious skin diseases represent a major global health burden, demanding effective and affordable treatments. Conventional therapies often face challenges such as reduced bioavailability, enzymatic degradation, low permeability, and poor solubility. Colloidal-based transdermal drug delivery systems, including liposomes, ethosomes, niosomes, nanoemulsions, polymeric nanoparticles, micelles, solid lipid nanoparticles, etc., have emerged as promising alternatives. In brief, these colloidal systems enhance drug penetration, stability, biocompatibility, and customized release while improving antimicrobial efficacy against various pathogens and minimizing systemic side effects. In conclusion, colloidal formulations offer a targeted, efficient approach, optimizing therapeutic outcomes, improving patient compliance, and advancing the treatment of infectious skin diseases.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102536"},"PeriodicalIF":4.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raffaele Palmieri , Luca Maurillo , Maria Ilaria Del Principe , Adriano Venditti , Francesco Buccisano
{"title":"Fitness in acute myeloid leukemia, state of the art and future directions","authors":"Raffaele Palmieri , Luca Maurillo , Maria Ilaria Del Principe , Adriano Venditti , Francesco Buccisano","doi":"10.1016/j.coph.2025.102527","DOIUrl":"10.1016/j.coph.2025.102527","url":null,"abstract":"<div><div>Acute Myeloid Leukemia (AML) is a complex disease whose outcome can be variably influenced by several clinical and biological factors. Although there is still no consensus on how to integrate these elements to best guide treatment choice, multiparametric models, commonly called fitness scores, have been developed to evaluate each patient's ability to tolerate therapies. These models consider various risk factors, including disease biology, comorbidities, physical and cognitive function. To date, several scoring systems can be used to categorize patients on their fitness for intensive or non-intensive therapies. However, existing tools mainly focus on identifying patients suitable for conventional intensive chemotherapy and fail to address the complexities of less-fit patients who might benefit from innovative intensive, less-intensive, and even maintenance strategies. As treatment landscapes are in constant evolution, identifying intermediate level of fitness through recalibration of existing scores or development of new ones should be prioritized. Considering all the above, this review aims to report on the state of the art of fitness assessment in AML and discuss possible future directions on this topic.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"83 ","pages":"Article 102527"},"PeriodicalIF":4.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bofei Wang , Patrick K. Reville , Hussein A. Abbas
{"title":"Therapeutic hurdles in acute myeloid leukemia: Leukemic stem cells, inflammation and immune dysfunction","authors":"Bofei Wang , Patrick K. Reville , Hussein A. Abbas","doi":"10.1016/j.coph.2025.102526","DOIUrl":"10.1016/j.coph.2025.102526","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is an aggressive and highly heterogeneous hematological malignancy characterized by clonal expansion and differentiation arrest in myeloid progenitor cells. Despite advancements in chemotherapy, allogeneic hematopoietic stem cell transplantation, and post-remission maintenance therapies, the long-term survival remains unsatisfactory with high rates of relapse and refractory. These therapeutic challenges are mediated by multiple factors, including the complexity of the cellular hierarchies in AML, the interaction of leukemic stem cells (LSCs) with the bone marrow niche, inflammation, and immune evasion mechanisms. Further, the absence of specific surface markers that distinguish LSCs from normal hematopoietic stem cells, together with LSCs’ functional heterogeneity, complicates targeted treatment approaches. Immune dysfunction, including T cell exhaustion and immune suppression within the bone marrow niche contributes to therapy resistance. In this brief review, we aim to explore current challenges in AML therapy, focusing on LSC-driven resistance, immune evasion, and the need for innovative therapeutic strategies.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102526"},"PeriodicalIF":4.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gordon Victor Hoffmann , Adrian Gottschlich , Marion Subklewe , Sebastian Kobold
{"title":"Novel approaches to CAR T cell target identification in acute myeloid leukemia","authors":"Gordon Victor Hoffmann , Adrian Gottschlich , Marion Subklewe , Sebastian Kobold","doi":"10.1016/j.coph.2025.102524","DOIUrl":"10.1016/j.coph.2025.102524","url":null,"abstract":"<div><div>Identifying safe and effective CAR T cell targets in acute myeloid leukemia (AML) is challenging due to the disease’s complexity and overlap with normal hematopoiesis. This review highlights advances in target discovery for AML, emphasizing innovative approaches. Structural surfaceomics identifies tumor-specific protein conformations, while AI-driven single-cell RNA sequencing integrates multi-source data to pinpoint optimal targets. Refined cell surface capture technology maps the AML surfaceome without relying on predefined antibodies. These strategies enhance CAR T cell specificity and minimize off-tumor effects, offering promising pathways for safer and more effective AML treatments and broader cancer therapies.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102524"},"PeriodicalIF":4.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Strategies to enhance anti-leukaemia immunotherapy","authors":"Memnon Lysandrou, Robert Zeiser","doi":"10.1016/j.coph.2025.102525","DOIUrl":"10.1016/j.coph.2025.102525","url":null,"abstract":"<div><div>Acute myeloid leukaemia (AML) was an incurable disease prior to allogeneic haematopoietic cell transplantation (allo-HCT), which was proven to be a potent cellular immunotherapy-approach. However, allo-HCT has major side effects, with disease relapse presenting as a frequent complication. Novel immunotherapies aim to reduce toxicity and increase the anti-leukaemia activity of allo-HCT. Technological advancements in genetic engineering approaches enable potent immunotherapeutic activity while limiting toxicities. A biology-driven application of small molecules that target AML vulnerabilities holds promise to enhance anti-leukaemia immunotherapy. Extensive preclinical testing of these approaches is essential to reduce toxicity and to find the ideal combination partners for future clinical testing.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102525"},"PeriodicalIF":4.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gregory T. Rognon , Anna Yu-an Liao , Rodahina Philihina Pasteurin , Avinash Soundararajan , Padmanabhan Paranji Pattabiraman
{"title":"Lipids and lipid regulators in intraocular pressure homeostasis","authors":"Gregory T. Rognon , Anna Yu-an Liao , Rodahina Philihina Pasteurin , Avinash Soundararajan , Padmanabhan Paranji Pattabiraman","doi":"10.1016/j.coph.2025.102523","DOIUrl":"10.1016/j.coph.2025.102523","url":null,"abstract":"<div><div>Increased intraocular pressure is the strongest correlated modifiable risk factor for developing primary open-angle glaucoma (POAG). Lipids have long been known to be a major constituent of aqueous humor. Lipid mediators, prostaglandins for example, are the first-line treatment for glaucoma. Innovative technologies have made the investigation of lipids in small quantities possible, and interest in identifying lipids as new pharmacological targets has grown in ophthalmology. There is expanding evidence to suggest that lipids and their active metabolites play a role in POAG pathophysiology, as differences between control and diseased eyes have now been demonstrated. The role of these differences is yet to be determined and is the subject of this review.</div></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102523"},"PeriodicalIF":4.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Balancing genome integrity and carcinogenesis: Insights into DNA damage response, repair pathways, and cancer therapies","authors":"Sudha Sharma, Srijita Dhar, Sagar Sengupta","doi":"10.1016/j.coph.2025.102522","DOIUrl":"10.1016/j.coph.2025.102522","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"82 ","pages":"Article 102522"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Message from the New Editor-in-Chief, Prof. Sheng-Tao Hou","authors":"Sheng-Tao Hou","doi":"10.1016/j.coph.2024.102504","DOIUrl":"10.1016/j.coph.2024.102504","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"80 ","pages":"Article 102504"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}