Acta Pharmaceutica Sinica B

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Mechanism of weight regain - The role of epigenetic modification in adipocytes

Acta Pharmaceutica Sinica B. 2025, 15(9): 4961-4963.
Chemical and genetic molecular glues to degrade CoREST corepressors

Acta Pharmaceutica Sinica B. 2025, 15(9): 4964-4966.
From synaptic gatekeepers to affective-cognitive modulators: The astrocyte D1 receptor-d-serine axis in the prefrontal cortex

Acta Pharmaceutica Sinica B. 2025, 15(9): 4967-4969.
Targeting PARylated RACK1/HIF-1α axis: A novel mechanism in acute kidney injury and therapeutic promise

Acta Pharmaceutica Sinica B. 2025, 15(9): 4970-4971.
Author correction to “Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways” [Acta Pharm Sin B 15 (2025) 2024-2038]

Acta Pharmaceutica Sinica B. 2025, 15(9): 4972-4972.
Resistance mutations and the blood-brain barrier: Key challenges in targeted treatment of brain metastatic non-small cell lung cancer

Acta Pharmaceutica Sinica B. 2025, 15(8): 3833-3851.

Over the past two decades, marked progress has been made in treating non-small cell lung cancer (NSCLC) patients with EGFR-, ALK-, ROS1- and KRASG¹²C-targeted inhibitors. NSCLC patients very often develop brain metastases. Despite the continuous development of newer and better inhibitors, the survival outcomes of NSCLC patients with brain metastases remain significantly worse than those of patients without. The main challenges in these pharmacotherapies are the development of resistance mutations, and, potentially, the presence of the blood-brain barrier (BBB). The outcomes of clinical studies show the improved efficacy of later-generation targeted inhibitors. The increase in progression free survival (PFS) in patients treated with these later-generation inhibitors is largely attributed to their efficacy against multiple resistance mutations, and possibly due to enhanced brain penetration. This review explores the different aspects hindering the targeted treatment of NSCLC and especially of brain metastases, focusing on recent clinical trials and emerging resistance mutations and the influence of the BBB on the efficacy of EGFR, ALK, ROS1 and KRASG¹²C inhibitors. The role of the ABCB1 and ABCG2 drug transporters in differential efflux of the targeted drugs at the BBB is also discussed, since preclinical studies indicate that they may reduce the efficacy of transported inhibitors.
Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects

Acta Pharmaceutica Sinica B. 2025, 15(8): 3852-3887.

Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.
Advances in immunoPET/SPECT imaging: The role of Fab and F(ab′)₂ fragments in theranostics

Acta Pharmaceutica Sinica B. 2025, 15(8): 3888-3924.

With the advent of precision medicine and personalized treatment, targeted therapies have become pivotal in oncology. Noninvasive molecular imaging, especially immunoPET/SPECT, plays a crucial role in refining cancer diagnostics and treatment monitoring by visualizing biological processes at the molecular level. This review explores the dynamic field of immunoPET/SPECT imaging using Fab and F(ab′)₂ fragments, characterized by advantageous pharmacokinetics and swift clearance from the bloodstream, making them suitable for same-day imaging procedures. We examine contemporary strategies for radiolabeling these fragments with PET and SPECT radionuclides and discuss potential advancements and the challenges anticipated in the further development of Fab and F(ab′)₂ fragments. Despite the complexities involved in their development, these fragments hold significant promise for advanceing personalized cancer treatment. Keys to this advancement are innovative radiolabeling techniques, site-specific conjugation chemistries, and short-lived radionuclides, all of which are crucial for overcoming existing limitations and enhancing the clinical utility of these imaging agents. As research progresses, Fab and F(ab′)₂ fragments are expected to become central to the future of cancer diagnostics and therapeutic monitoring, thereby improving patient management and contributing significantly to the evolution of personalized medicine.
Blades and barriers: Oral vaccines for conquering cancers and warding off infectious diseases

Acta Pharmaceutica Sinica B. 2025, 15(8): 3925-3950.

Global public health faces substantial challenges from malignant tumors and infectious diseases. Vaccination provides an approach for treating and preventing these diseases. Oral vaccinations are particularly advantageous in disease treatment and prevention due to their non-invasive nature, high patient compliance, convenience, cost-effectiveness, and capacity to stimulate comprehensive and adaptive immune responses. However, the overwhelming majority of oral vaccines remain in experimental development, struggling with clinical and commercial translation due to their suboptimal efficacy. Thus, enhancing scientists’ understanding of the interaction between vaccines and gastrointestinal immune system, creating antigen delivery systems suitable for the gut mucosal environment, developing more potent antigenic epitopes, and using personalized combination therapies are critical for advancing the next generation of oral vaccines. This article explores the fundamental principles and applications of current oral anti-tumor and anti-infective vaccines and discusses considerations necessary for designing future oral vaccines.
Engineering strategies of sequential drug delivery systems for combination tumor immunotherapy

Zhenyu Xu, Siyan Liu, Yanan Li, Yanping Wu, Jiasheng Tu, Qian Chen, Chunmeng Sun

Acta Pharmaceutica Sinica B. 2025, 15(8): 3951-3977.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

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