Renal cell carcinoma (RCC) is a highly vascularized and metastatic malignancy of the kidney. The 5-year overall survival rate of RCC patients remains poor despite the development of therapeutic modalities. Therefore, identifying novel approaches to increase the sensitivity of RCC cells to drugs could help prolong patient survival. Recently, Drug repurposing, which leverages the established safety profiles and pharmacological properties of existing medications, has emerged as a promising alternative to traditional drug development. This approach can accelerate the translation of new therapies into clinical practice and is often associated with lower attrition rates in clinical trials. Recent evidence supports the therapeutic potential of various repurposed drugs against RCC. This review article summarizes and shows the effectiveness and potential of repurposed drugs including metabolic and cardiovascular modulators (metformin, simvastatin), antimicrobial and antiparasitic agents (artesunate, ivermectin, ketoconazole, chloroquine, hydroxychloroquine, niclosamide, doxycycline, pentamidine), mTOR inhibitors (temsirolimus, everolimus, rapamycin), anti-inflammatory and analgesic agents (aspirin, celecoxib), and agents with other mechanisms of action (acetazolamide, disulfiram). These agents exert their anticancer effects against RCC by modulating multiple signaling pathways, including PI3K/AKT/mTOR, AMPK, JAK2/STAT3, ERK1/2, Wnt/β-catenin, and RhoA/ROCK, as well as by inducing autophagy inhibition, ferroptosis, oxidative stress, and mitochondrial dysfunction, highlighting their utility in RCC therapy and emphasizing their clinical relevance.

Cellular senescence is a dynamic stress response with broad implications in aging, tissue homeostasis, and disease. In anti-cancer therapies, senescence acts as a double-edged sword, initially suppressing tumor growth but contributing to therapy tolerance and minimal residual disease, later leading to tumor repopulation, and relapse. While senescent cells are the seat of a large-scale metabolic reprogramming, the specific contribution of O-GlcNAcylation, a nutrient-sensitive post-translational modification involved in cancer progression and therapy resistance, was only recently investigated. Here, we first summarize studies reporting changes in O-GlcNAcylation levels during senescence and how modulation of O-GlcNAc cycling enzymes influences senescence onset, maintenance, and escape. We then discuss evidence suggesting that O-GlcNAcylation may influence several hallmarks of senescence, including cell cycle arrest, DNA damage response, apoptosis resistance, metabolic rewiring and mitochondrial stress signaling. Finally, we discuss the potential therapeutic relevance of targeting O-GlcNAc cycling enzymes to modulate cancer cell senescence, limit senescence escape, and thereby improve anti-cancer treatment responses.

In the era of precision medicine, targeting resistance mechanisms is a rational approach to optimize treatment management based on tumor molecular profiling, with the goal of improving clinical outcomes. However, the role of tailored strategies in the treatment algorithm of EGFR-mutated NSCLC remains incompletely defined.

Bicaudal-C homolog 1 (BICC1) is an essential RNA-binding protein that plays a significant role in cellular signaling and gene expression regulation. Recent research has linked the BICC1 gene to the initiation and advancement of tumors. Current investigations primarily aim to elucidate its structural characteristics and functional roles, while its precise involvement in tumorigenesis and its viability as a therapeutic target are still being explored. This review delves into the structure and functions of BICC1, emphasizing its participation in tumor cell growth, programmed cell death, epithelial-mesenchymal transition (EMT), blood vessel formation, maintenance of stem cells, and chemoresistance. Furthermore, it examines progress in developing drugs that target BICC1 for cancer therapy and evaluates the potential advantages of traditional Chinese medicine in mediating anti-tumor effects through BICC1 modulation, offering perspectives for future targeted treatment strategies.

Despite the clinical success of immune checkpoint inhibitors (ICIs), resistance driven by a metabolically hostile tumor microenvironment (TME), particularly lipid metabolic reprogramming, remains a formidable challenge. Tumors actively exploit lipid mediators, notably prostaglandin E2 (PGE2), to suppress CD8+ T cells and promote immunosuppressive macrophage polarization. Although targeted nanotherapeutics aim to locally reverse these defects, their in vivo efficacy is frequently abrogated by the host's nutritional baseline. Specifically, high dietary intake of Omega-6 polyunsaturated fatty acids fuels systemic PGE2 biosynthesis, creating a metabolic "sink" that localized nanotherapies struggle to neutralize. To address this limitation, this review proposes a dual-compartment therapeutic framework combining systemic dietary modulation with precision nanotherapy. As a distinctive contribution, we bridge these biological mechanisms with pharmaceutical design by integrating critical translational barriers, advanced formulation strategies, and emerging technologies for lipid reprogramming. Building upon this, we critically evaluate the most promising formulations, including stimuli-responsive and lipid-targeted nanocarriers, to elucidate their synergistic potential with nutritional interventions. Ultimately, pairing systemic Omega-3 dietary preconditioning with localized nanotherapeutics provides a biologically rational strategy to dismantle lipid-driven immune evasion. Maximizing patient outcomes and advancing future clinical prospects will depend on the rigorous translation of these combinatorial regimens to effectively overcome ICI resistance.

A major limitation of conventional two and three-dimensional preclinical in vitro cancer models is their inability to reproduce the drug-delivery barriers. Tumor assembloids, which integrate patient-derived cancer cells with stromal, endothelial, and immune components in three-dimensional architectures, provide a manipulable framework for simulating these multicellular impediments. This review specifically examines the application of tumor assembloids to investigate drug delivery constraints, including stromal exclusion, vascular transport, immune-mediated resistance, penetration gradients, and spatially heterogeneous drug exposure. We compared three major construction strategies, including self-assembly, 3D bioprinting, and microfluidic compartmentalization, and evaluated their respective strengths for drug assessment. We also discussed assembloids' current limitations, including reproducibility, incomplete physiological dynamics, insufficient spatial analytics, and the need for standardized benchmarking. Overall, tumor assembloids represent promising mechanistic platforms for studying tumor drug delivery barriers. However, broader clinical application will necessitate rigorous validation and harmonized assay standards.

Marine natural products have attracted considerable attention owing to their diverse biological activities and unique structural features. Among them, the dragmacidin alkaloids represent a structurally intriguing family of marine-derived natural products. These alkaloids exhibit a wide range of biological activities, including anticancer and antimicrobial activities, which have stimulated significant interest from both the chemical and biological communities. Structurally, they are characterized by highly functionalized bisindole frameworks in which two indole units are connected via a piperazine, pyrazine, or pyrazinone ring, and can be classified into three categories based on the nature of the linking unit: (i) dragmacidin and dragmacidins A, B, C, I, J, and didebromodragmacidin, featuring a piperazine linker; (ii) dragmacidins D, E, and F, containing a pyrazinone linker; and (iii) dragmacidins G and H, incorporating a pyrazine linker. These structural features pose formidable challenges for chemical synthesis, and consequently, the dragmacidin family has served as an important platform for the development of new synthetic strategies. In this chapter, we provide a comprehensive overview of the dragmacidin alkaloids, focusing on their isolation, structural features, biological activities, and synthetic studies.

The emerging advance of targeted protein degradation (TPD) technology offers a novel option for protein modulation, ensuring a more durable and precise therapeutic impact for cancer management. While promising, complete degradation of the proteins of interest (POIs) in both pathological and normal tissues may cause severe side effects. Furthermore, insufficient accumulation of the protein degraders at the target tissues also limits the clinical translation of TPD. It remains an unmet need to achieve spatiotemporally tunable degradation of the POI at the tumor lesion. In recent years, our group has extensively exploited the potential of the stimuli-activatable TPD technology for precise cancer therapy. The stimuli-activatable protein degraders were rationally designed for achieving tumor-specific enrichment in vivo to maximize their therapeutic effects while minimizing the side effects. Several kinds of stimuli-labile prodrugs of the proteolysis targeting chimeras (PROTACs) were rationally designed for restoring their protein degradation functions with the endogenous or exogenous stimulus of tumor while remaining "silent" elsewhere, resulting in precise therapies and reduced side effects. Leveraging the advantages of nanomedicine delivery systems, several kinds of tumor acidity and enzymatic-activatable nanodegraders were developed to achieve tumor-targeted protein degrader distribution and POI degradation. In particular, photothermally activatable protein degraders were developed to perform spatiotemporally controllable degradation of various POIs. In this Account, we systematically summarize recent advances from our group regarding the rational design of stimuli-activatable protein degraders, and strategically outline the "when and how" of integrating these degraders with nanomedicine platforms to tailor precise cancer therapy. We discuss the crucial role of the tumor microenvironment-responsive moieties for stimuli-triggered degradation of both intracellular and membrane POIs, highlighting the distinct design rationale for their respective prodrugs. Furthermore, we summarize our advances of strategic integration of the TPD technology with nanomedicine to augment the therapeutic outcomes of phototherapy, radiotherapy, chemotherapy, and immunotherapy of solid tumors. It is envisaged that the tumor microenvironment-activatable protein degradation approaches will achieve tumor-specific protein degradation and precision therapy, thereby facilitating the clinical application of TPD. By outlining optimized design strategies and future challenges, this Account aims to serve as a roadmap for researchers seeking to develop next-generation activatable TPD technologies that are modular, functionally versatile, and translatable.

Cancer therapy has advanced substantially through targeted therapies and immunotherapy; however, durable clinical responses remain limited by the development of drug resistance. Increasing evidence identifies cancer stem cells (CSCs) as central drivers of therapeutic failure, tumor recurrence, metastasis, and minimal residual disease. CSCs possess self-renewal and differentiation capacities together with remarkable adaptability under therapeutic stress, enabling long-term tumor maintenance and regeneration. CSC-mediated resistance arises through coordinated intrinsic and extrinsic mechanisms. Intrinsically, CSCs employ multiple survival programs, including cellular quiescence, enhanced DNA damage response and repair, ATP-binding cassette transporter-mediated drug efflux, apoptosis evasion, and metabolic reprogramming. Extrinsically, these mechanisms are reinforced through dynamic interactions with the tumor microenvironment (TME), particularly hypoxic and perivascular niches that support stemness and therapeutic tolerance. Importantly, CSCs are increasingly recognized as dynamic cellular states rather than fixed populations and exhibit marked plasticity through reversible transitions between stem-like and non-stem states, frequently mediated by epithelial-mesenchymal transition (EMT). This plasticity promotes intratumoral heterogeneity and replenishes resistant cell populations. In this review, we provide a comprehensive synthesis of the molecular and microenvironmental mechanisms underlying CSC-driven drug resistance and critically discuss emerging therapeutic strategies targeting CSC plasticity, niche interactions, metabolic adaptation, and immune evasion. Collectively, these insights support the development of integrated multi-target therapeutic approaches to improve long-term clinical outcomes.

RGPR-p117 was identified as a transcription factor that binds to the TTGGC(N)6CC sequence in the promoter region of the regucalcin gene, a tumor suppressor. This article discusses the therapeutic potential of targeting RGPR-p117 in cancer cells.

Cancer is a leading cause of death worldwide, affecting individuals of reproductive age. Although conventional treatments are essential for cure and survival improvement, they adverse effects on male and female fertility. This systematic review, registered in PROSPERO (CRD42024538296) and conducted according to PRISMA guidelines, aimed to evaluate the impact of these treatments on the reproductive system of murine animal models. A literature search across PubMed, Scopus, Web of Science, and Embase yielded 30 included studies. Most studies used C57BL/6 J and Wistar rats. The most frequently drugs were cyclophosphamide, cisplatin, and doxorubicin, which were mainly administered intraperitoneally at varying doses. Assessed outcomes included sperm analysis, ovulation rate, reproductive efficiency, histological alterations, and gene expression. Alkylating agents caused significant testicular degeneration and follicular toxicity, severely impairing fertility. Antimetabolites and antineoplastic antibiotics induced severe reproductive damage in both sexes. Topoisomerase and microtubule inhibitors demonstrated relevant reproductive toxicity, although data are limited. In women, alterations in ovarian and uterine functions are observed, and in men, the effects range from dysfunctions of the hypothalamic-pituitary-gonadal axis to alterations in the structural and functional integrity of gametes. Both radiotherapy and chemotherapy target cellular DNA; however, they act through distinct mechanisms. Most studies are with males, and studies with females, when present, often lacked comprehensive evaluation. The methodological quality assessment shows a lack of blinding and allocation concealment. In general, the studies focused on doses, treatment regimens, and experimental protocols. Therefore, conventional treatments negatively affect fertility in murine models, highlighting need for fertility preservation strategies in cancer patients.

Spatholobus suberectus Dunn (SSD), known in traditional Chinese medicine as Jixueteng, has historically been used to treat conditions characterized by blood stasis. Modern research has validated its anticancer potential. Recent studies reveal broad-spectrum antiviral activity.

Cyanobacteria are ancient photosynthetic Gram-negative prokaryotes widely distributed in various aquatic environments, exhibiting strong adaptability and the capacity to produce a diverse range of secondary metabolites. Among these metabolites, different types of peptides, including linear and cyclic peptides, are the dominant compounds. Although a number of in-depth studies on various linear peptides originating from cyanobacteria have been published, there has not yet been a comprehensive review that systematically summarizes the diverse research on these linear peptides. This article provides a systematic overview of the research progress on 19 classes of well-studied cyanobacteria-derived linear peptides, including short chain linear peptides, fatty acid modified linear peptides, linear peptides containing specialized cyclic moieties and long chain linear peptides, focusing on their biogenesis, structural diversity, biosynthesis as well as bioactivities. These linear peptides have emerged as promising candidates for developing anticancer, anticoagulant, anti-inflammatory and antiparasitic agents due to their versatile bioactivities and structural modifiability. Integrated chemical and biosynthetic strategies offer novel approaches to enhance production efficiency and optimize the pharmacological properties of these peptides. Future research will focus on overcoming the stability limitations of these linear peptides and expanding their therapeutic applications, aiming to unlock their full potential in addressing unmet medical challenges.

In current intensive care units (ICUs), advanced cutaneous melanoma is no longer merely a terminal complication, but has evolved into a dynamic treatment-related syndrome. Immune checkpoint inhibitors can achieve durable disease control, but they may trigger fulminant multi-organ toxicity, requiring rapid identification and intervention to preserve anti-tumor benefits. BRAF/MEK targeted therapy enables rapid tumor debulking, but it easily induces severe events such as hyperprogression and tumor lysis syndrome due to drug resistance. Cellular therapies like tumor-infiltrating lymphocytes (TILs) offer new options for patients with previous treatment failure, but also bring ICU-related risks including cytokine release syndrome. This review proposes that ICUs should serve as upstream collaborators in melanoma care. It outlines key diagnostic and therapeutic pathways for various emergencies based on four core principles: toxicity recognition, standardized intervention, dynamic risk monitoring, and safe restart of systemic therapy. It also notes that future individualized management can be realized by integrating multi-dimensional indicators, to coordinate short-term organ support and long-term disease control, and improve the survival prognosis and quality of life of critically ill patients with melanoma.

Olanzapine is an established antiemetic for the prevention of chemotherapy-induced nausea and vomiting (CINV), although the optimal dose for balancing efficacy and tolerability remains uncertain. We conducted a systematic review and network meta-analysis comparing olanzapine 2.5 mg, 5 mg, and 10 mg for CINV prophylaxis.

Isothiocyanates (ITCs) are naturally occurring organo-sulfur compounds. They occur widely in different plant sources, being most abundant in Brassicaceae family. Several of them have been demonstrated to possess significant bioactivities and health benefits including anticancer, anti-inflammatory, and antimicrobial activities. ITCs have very high electrophilicity and nucleophilicity due to the carbon and sulfur atom, respectively. Thus, chemical structure plays a prominent role in their bioactivities and ability to inhibit tumorigenesis. ITCs are potent against many forms of cancers and tumors. ITCs as drug conjugates and in combination therapies as antitumor therapeutic agents have shown promising prospects for clinical applications. Evaluation of possible ways to retain and/or enhance conversion of plant-derived GLSs into beneficial ITCs, can aid in enhancing nutritive and anticancer properties of ITC rich dietary plant sources. This review presents a comprehensive account of ITCs, their structure-activity relationship, specific biological functions to inhibit tumorigenesis and mechanism of action of different ITCs. Some examples on the use of ITC-drug conjugates and their use in combination therapies as promising anticancer therapeutics are highlighted. Further, methods to enhance nutritive properties through the conversion of glucosinolates (GLSs) into beneficial ITCs have also been proposed.

Immune checkpoint inhibitors are widely used in the treatment of malignant tumors. Although the incidence rate of type 1 diabetes induced by these inhibitors is low, the damage to pancreatic β cells is irreversible and the treatment effect of steroids is poor, which requires clinical attention. This article reports a case of a 69-year-old patient with poorly differentiated adenocarcinoma of the stomach and colon who developed this disease during treatment with Sintilimab combined with the SOX regimen. After insulin treatment, her blood glucose levels gradually stabilized. Based on the literature, we explore the pathogenesis, diagnostic difficulties, and current treatment status centered around insulin replacement therapy. We emphasize the need for clinicians to strengthen blood glucose monitoring during treatment with immune checkpoint inhibitors, identify symptoms early, and optimize diagnosis and treatment to improve patient prognosis.

Immune checkpoint inhibitors (ICIs) enhance antitumor immunity but can disrupt immune tolerance, leading to immune-related adverse events (irAEs) affecting multiple organs. Simultaneous life-threatening multiorgan irAEs remain rare and poorly characterized, particularly in head and neck cancer.

Colorectal cancer (CRC) with a deficient mismatch repair and high microsatellite instability (dMMR-MSI-H) phenotype represents a biologically distinct subtype characterized by elevated tumor mutational burden and strong immunogenicity. These features contribute to their exceptional responsiveness to immune checkpoint inhibitors (ICIs), especially those targeting the PD-1 and CTLA-4 pathways. Although dMMR-MSI-H tumors constitute only a small fraction of CRC cases, their response to ICIs has redefined therapeutic standards. In this review, we discuss the immunological underpinnings that render these tumors susceptible to immune modulation, summarize key clinical trial findings, and analyze emerging resistance mechanisms. Furthermore, we highlight the evolving landscape of predictive biomarkers and ongoing efforts to increase treatment efficacy through combination strategies and biomarker-driven approaches.

HER2-positive gastric and gastroesophageal junction (GEJ) cancers have poor prognosis despite standard trastuzumab-based chemotherapy. Immune checkpoint inhibitors (ICIs) may enhance therapeutic efficacy when combined with trastuzumab.