Chemotherapy resistance and immunosuppression are major causes of tumor treatment failure. The polarization state of tumor-associated macrophages (TAMs) is a central regulatory hub for both processes. Traditional Chinese medicine (TCM) has the characteristics of multi-component, multi-target, and multi-pathway. It regulating M1/M2 polarization is promising due to the high plasticity of TAMs. This review comprehensively explores the anti-tumor effects of TCM active components through multiple targets such as metabolic reprogramming. The mechanism includes regulating TAM's polarization, reversing chemotherapy resistance, and modulating immunosuppression. Furthermore, we also summarize the synergistic effects of TCM multi-component and the exploration of mechanisms promoted by new technologies. While most studies are still in the preclinical stage, these insights highlight the potential of TCM as a cancer treatment and highlight avenues for future research and clinical application to improve patient outcomes.

Ginsenoside Rg3, as one of the major active components of Panax ginseng, exhibits significant anti-tumor, anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, wound healing and immunomodulatory pharmacological effects and has been developed as an adjuvant therapy in clinical practice. However, its poor water solubility and low permeability result in limited bioavailability, restricting its clinical application. This review systematically summarizes the pharmacological mechanisms of ginsenoside Rg3, including its anti-tumor effects through multiple signaling pathways that inhibit cancer cell proliferation, induce apoptosis, and suppress tumor angiogenesis; anti-inflammatory properties via the inhibition of NF-κB and related factors; antioxidant effects by increasing antioxidant enzyme levels and regulating the Nrf2 pathway; antidiabetic effects via the promotion of insulin secretion by inhibiting the MAPK pathway; hepatoprotective effects via the attenuation of hepatic inflammation through suppressing NF-κB phosphorylation; wound-healing-promoting effects via modulating the TGF-β/SMAD signaling pathway, and immunomodulatory activities through immune cell regulation and inhibition of PD-L1 glycosylation. Additionally, this review discusses the pharmacokinetic properties of Rg3, such as rapid oral absorption but low plasma concentration and bioavailability. Furthermore, this review highlights various drug delivery systems, including liposomes, solid dispersions, cyclodextrin inclusion complexes, microspheres, electrospun nanofiber membranes, hydrogels, nanoparticles, micelles, and microneedles, which have been developed to improve its physicochemical properties and enhance its therapeutic efficacy. By systematically summarizing the pharmacological mechanisms and formulation optimization strategies of Rg3, this review provides theoretical insights and technical support for future research and clinical translation.

The role of artificial intelligence (AI) in cancer drug discovery and development has garnered significant attention due to its potential to transform the traditionally time-consuming and expensive processes involved in bringing new therapies to market. AI technologies, such as machine learning (ML) and deep learning (DL), enable the efficient analysis of vast datasets, facilitate faster identification of drug targets, optimization of compounds, and prediction of clinical outcomes. This review explores the multifaceted applications of AI across various stages of cancer drug development, from early-stage discovery to clinical trial design, development. In early-stage discovery, AI-driven methods support target identification, virtual screening (VS), and molecular docking, offering precise predictions that streamline the identification of promising compounds. Additionally, AI is instrumental in de novo drug design and lead optimization, where algorithms can generate novel molecular structures and optimize their properties to enhance drug efficacy and safety profiles. Preclinical development benefits from AI's predictive modeling capabilities, particularly in assessing a drug's toxicity through in silico simulations. AI also plays a pivotal role in biomarker discovery, enabling the identification of specific molecular signatures that can inform patient stratification and personalized treatment approaches. In clinical development, AI optimizes trial design by leveraging real-world data (RWD), improving patient selection, and reducing the time required to bring new drugs to market. Despite its transformative potential, challenges remain, including issues related to data quality, model interpretability, and regulatory hurdles. Addressing these limitations is critical for fully realizing AI's potential in cancer drug discovery and development. As AI continues to evolve, its integration with other technologies, such as genomics and clustered regularly interspaced short palindromic repeats (CRISPR), holds promise for advancing personalized cancer therapies. This review provides a comprehensive overview of AI's impact on the cancer drug discovery and development and highlights future directions for this rapidly evolving field.

Tumor immune glucans (TIGs) are emerging as promising anticancer agents capable of enhancing immune responses and mitigating the side effects of chemotherapy. This review analyzes 59 TIGs published between 2015 and 2025, focusing on their isolation, structural characterization, structure-activity relationships, and pharmacological mechanisms. Literature searches were conducted in databases such as Web of Science, PubMed, Google Scholar, Embase, Cochrane Library, ClinicalTrials.gov and CNKI using keywords including "glucans", "tumor immunity", and "polysaccharide structure," covering studies in both English and Chinese. The review highlights the relationship between the structural features of TIGs and their antitumor activities.1,3-linked β-glucans surpassed 1,4-linked or 1,6-linked configurations in antitumor immunostimulatory activity. Elevated molecular weight enhances the structural robustness of TIGs chains, facilitating their selective recognition by cellular receptors and amplifying their anti-tumor immune responses. TIGs exert antitumor effects through mechanisms such as immunomodulation, inhibition of tumor immune escape, and remodeling of the tumor microenvironment, involving signaling pathways such as TLRs/NF-κB, JAK/STAT, MAPK, Bax/Bcl-2, PI3K/Akt, and VEGF/VEGFR. Despite their promising therapeutic potential, challenges remain, including incomplete structural characterization, insufficient IC50 value data, and a lack of reference drugs. Many studies focus on cytokine levels and cellular activity, but deeper molecular mechanistic insights are needed. Further research into the mechanisms of action and targets of TIGs may pave the way for new cancer treatment strategies.

Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, characterized by dysregulated signaling pathways. Many Sophora compounds exhibit potential anti-NSCLC properties. However, the research status, particularly regarding the underlying mechanisms, remains fragmented.

This review aims to comprehensively assess the health benefits and pharmacological activities of hesperidin, a flavonoid commonly found in citrus fruits. It consolidates recent research findings to provide insights into hesperidin's diverse health-promoting effects.

Fumarate hydratase-deficient renal cell carcinoma (FHdRCC) is a rare and aggressive form of kidney cancer that presents significant therapeutic challenges. Due to its rarity, treatment decisions often rely on comprehensive literature reviews to identify potential therapeutic options. This article presents a case of a 37-year-old patient with metastatic FHdRCC who showed partial response to Nivolumab but experienced persistent lymphatic involvement and symptoms requiring ongoing intervention. The clinical team sought to evaluate alternative combination therapies through a literature review. Elicit, an AI-powered research assistant, was employed to structure the literature review process through an automated analysis of scientific papers. This case served as a test of Elicit's capabilities in synthesizing treatment options for rare cancers, compared to traditional research methodologies. The platform demonstrated significant limitations in its search capabilities due to restricted database access. However, it showed efficiency in analyzing provided papers and organizing clinical data by key categories. These findings suggest that while Elicit may serve as a helpful support tool for literature analysis, it is best used as a complement to traditional search methods, with careful verification of its output by clinical experts. Disclosures: Dolev Vaknin, Or Degany, Rotem Sisso-Avron, and Prof. Sharon Einav are employed by Medint Medical Intelligence, which conducted the literature review that served as the basis for this paper.

In recent years, metabolic reprogramming has emerged as a significant breakthrough in elucidating the onset and progression of gastrointestinal (GI) malignancies. As central regulatory hubs for lipid metabolism, sterol regulatory element binding proteins (SREBPs) integrate dietary metabolic signals and carcinogenic stimuli through subtype-specific mechanisms, thereby promoting malignant tumour phenotypes. In this review, we first present the molecular background, structural characteristics, and posttranscriptional regulatory networks associated with SREBPs. We subsequently describe a systematic analysis of the distinct activation patterns of SREBPs in liver, gastric, colorectal, and other gastrointestinal cancers. Furthermore, we explore targeted intervention strategies for different SREBP subtypes, including small molecule inhibitors (such as fatostatin, which inhibits SREBP cleavage), natural compounds (such as berberine, which modulates the AMPK/mTOR pathway), and statin-mediated inhibition of the mevalonic acid pathway. These strategies may enhance tumour cell sensitivity to chemotherapeutic agents (such as 5-FU, gezil, and tabine) and improve the response to synergistic chemoradiotherapy by reversing adaptive metabolic resistance driven by the tumour microenvironment. Through this review, we hope to provide new insights into precise interventions targeting various subtypes of the SREBP molecule.

Cancer remains a significant global health burden due to its high morbidity and mortality. Oncogene-targeted therapy and immunotherapy have markedly improved the 5-year survival rate in the patients with advanced or metastatic tumors compared to outcomes in the era of chemotherapy/radiation. Nevertheless, the majority of patients remain incurable. Initial therapies eliminate the bulk of tumor cells, yet residual populations termed drug-tolerant persister cells (DTPs) survive, regenerate tumor and even drive distant metastases. Notably, DTPs frequently render tumor cross-resistance, a detrimental phenomenon observed in the patients with suboptimal responses to subsequent therapies. Analogous to species evolution, DTPs emerge as adaptative products at the cellular level, instigated by integrated intracellular stress responses to therapeutic pressures. These cells exhibit profound heterogeneity and adaptability shaped by the intricate feedforward loops among tumor cells, surrounding microenvironments and host ecology, which vary across tumor types and therapeutic regimens. In this review, we revisit the concept of DTPs, with a focus on their generation process upon targeted therapy or immunotherapy. We dissect the critical phenotypes and molecule mechanisms underlying DTPs to therapy from multiple aspects, including intracellular events, intercellular crosstalk and the distant ecologic pre-metastatic niches. We further spotlight therapeutic strategies to target DTP vulnerabilities, including synthetic lethality approaches, adaptive dosing regimens informed by mathematical modeling, and immune-mediated eradication. Additionally, we highlight synergistic interventions such as lifestyle modifications (e.g., exercise, stress reduction) to suppress pro-tumorigenic inflammation. By integrating mechanistic insights with translational perspectives, this work bridges the gap between DTP biology and clinical strategies, aiming for optimal efficacy and preventing relapse.

Pterostilbene (PT), a natural dimethoxy analogue of resveratrol, exhibits enhanced bioavailability and lipophilicity, making it a more effective therapeutic candidate than resveratrol. These pharmacokinetic advantages improve its cellular uptake and metabolic stability, positioning PT as a promising compound in cancer treatment. PT has shown significant anticancer activity in several malignancies, including melanoma, breast, colorectal, and ovarian cancers. Its mechanisms of action include induction of apoptosis through caspase activation, cell cycle arrest, and inhibition of angiogenesis and metastasis via downregulation of matrix metalloproteinase-9 and vascular endothelial growth factor. PT also modulates epigenetic processes such as DNA methylation and histone modifications, and targets cancer stem cells by reducing the expression of stemness markers like CD44 and c-Myc. Additionally, PT enhances the efficacy of standard chemotherapeutic agents such as cisplatin, doxorubicin, and 5-fluorouracil, with preclinical studies showing synergistic effects and reversal of drug resistance. A Phase II clinical trial (NCT03671811) in endometrial cancer patients has confirmed the safety of PT and revealed its ability to modulate immune-related gene expression and suppress mechanistic target of rapamycin (mTOR) signaling. Despite promising results, several challenges remain particularly low water solubility, limited systemic bioavailability, lack of large-scale human studies, and undefined therapeutic protocols. Future research should focus on advanced formulation strategies, rigorous clinical trials across cancer types, and identification of patient-specific therapeutic responses to support PT's integration into oncology practice.

The standard treatments for prostate cancer (PCa) include chemotherapy, hormone therapy, targeted therapies based on androgen receptor (AR) and/or gonadotropin-releasing hormone (GnRH) receptor antagonists, and radiation therapy. But PCa therapeutic resistance remains an unsolved challenge, leading to progression to castration-resistant prostate cancer (CRPC). Emerging PCa therapies - including poly(ADP-ribose) polymerase (PARP) inhibitors, AR crosstalk signalling pathway inhibitors, B-cell lymphoma 2 (BCL-2) inhibitors, cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitors, CRISPR/Cas9, epigenetic inhibitors, and nanotechnology-based drug-delivery approaches - provide promising targeted solutions. Targeted protein degradation therapy, particularly AR degradation therapies, effectively inhibits resistance at its source. This review summarises the established and emerging PCa therapies, focusing on discussing their efficacy in terms of PCa resistance with supporting experimental findings and the mechanisms of PCa drug resistance.

The use of metallodrugs in cancer therapy received widespread interest after the successful application of cisplatin and its analogous compounds as chemotherapeutic medications. Despite the development of various metallodrugs in past years, platinum-based chemotherapeutic agents are the only clinically approved metallodrugs that primarily interact with genomic DNA and trigger severe dose-limiting adverse side effects in cancer patients. As a consequence, the advancement of new risk-free metallodrugs has become a topmost concern in cancer research to minimize toxicity and improve therapeutic outcomes. G-quadruplex (G4) DNA structures have recently come to light as an attractive drug target in cancer therapy because of their gene regulation ability and role in maintaining genomic stability. Their presence in telomere and promoter region of oncogenes has the potential to induce apoptosis in cancer cells through the inhibition of telomerase activity and gene expression. Therefore, the development of new G4 DNA targeting small molecular entities including metal complexes came out as a viable approach for uprooting cancer disease. Beyond organic small molecules, innumerable metal complexes have been developed in past years to target G4 DNA structures in the context of cancer therapy. This review primarily aims to highlight these metal complexes through a comprehensive discussion about their structural properties, their binding interactions with G4 DNA, their cancer cell growth inhibition mechanisms, and their efficacy in both cellular and in vivo systems, to decode their potential as anti-cancer drugs. Additionally, the potential of these metal complexes in the field of bio-imaging and photodynamic therapy is also explored.

Cancer is the second leading cause of mortality worldwide. Despite the available treatment options, a majority of cancer patients develop drug resistance, indicating the need for alternative approaches. Repurposed drugs, such as antiglycolytic and anti-microbial agents, have gained substantial attention as potential alternative strategies against different disease pathophysiologies, including lung cancer. To that end, multiple studies have suggested that the antiglycolytic dichloroacetate (DCA) and the antibiotic salinomycin (SAL) possess promising anticarcinogenic activity, attributed to their abilities to target the key metabolic enzymes, ion transport, and oncogenic signaling pathways involved in regulating cancer cell behavior, including cell survival and proliferation. We used the following searches and selection criteria. (1) Biosis and PubMed were used with the search terms dichloroacetate; salinomycin; dichloroacetate as an anticancer agent; salinomycin as an anticancer agent; dichloroacetate side effects; salinomycin side effects; salinomycin combination therapy; dichloroacetate combination therapy; and dichloroacetate or salinomycin in combination with other agents, including chemotherapy and tyrosine kinase inhibitors. (2) The exclusion criteria included not being related to the mechanisms of DCA and SAL or not focusing on their anticancer properties. (3) All the literature was sourced from peer-reviewed journals within a timeframe of 1989 to 2024. Importantly, experimental studies have demonstrated that both DCA and SAL exert promising anticarcinogenic properties, as well as having synergistic effects in combination with other therapeutic agents, against multiple cancer models. The goal of this review is to highlight the mechanistic workings and efficacy of DCA and SAL as monotherapies, and their combination with other therapeutic agents in various cancer models, with a major emphasis on non-small-cell lung cancer (NSCLC) treatment.

Sonodynamic therapy (SDT), characterized by its non-invasiveness, low toxicity, and deep tissue penetration, has emerged as a promising therapeutic modality for anticancer treatments. Recently, covalent organic frameworks (COFs) have garnered significant attention in the SDT realm as a powerful and versatile toolbox. Notably, COF-based SDT has achieved many encouraging outcomes owing to the remarkable potential of COFs, and the volume of related research has experienced continuous growth. Therefore, we strive to provide a timely and comprehensive review that thoroughly summarizes the advancements in COF-based SDT. This review begins with a concise yet comprehensive summary of ultrasonic cavitation and sonodynamic effects, elucidating the fundamental principles and potential mechanisms of SDT. Subsequently, it delves into the chemistry of COFs, examining intricate structure designs, various types of linkages, and diverse synthetic methods. The primary focus of this review is to summarize COF-based sonosensitizers, including construction strategies and product properties. More importantly, the role of COFs in SDT combined therapies is described in detail, aiming to highlight the advantages of COF-enhanced SDT and synergistic treatments. Finally, the review points out the current challenges and future opportunities in this rapidly evolving research field. Overall, the deliberations and overviews of COF-based sonosensitizers and SDT strategies are expected to facilitate advancements, leading to early-stage clinical benefits for patients.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, particularly melanoma. However, immune-related adverse events (irAEs) pose significant challenges, particularly in cases of severe toxicity syndromes. One such life-threatening irAE is the myocarditis, myositis, and myasthenia gravis (MMM) overlap syndrome, which occurs in less than 1% of patients but has in-hospital mortality rates ranging from 40 to 60%. Due to its rarity and complexity, early recognition and a multidisciplinary approach are critical to improving outcomes.

Lung cancer is the cancer with the highest incidence and mortality rate worldwide. In addition to the diversified treatment and prolonged lifespan in view of the development of medical technology, the side effect of medicine should not be ignored. Drug-induced interstitial lung disease (DI-ILD) is also commonly encountered during this process, and ILD triggered by the treatment of lung cancer characterized by the inflammation and scarring of lung tissue after the antitumor treatment in lung cancer leads to a poor prognosis and high mortality. The diagnosis and treatment of ILD caused by anti-lung cancer agents remains challenging in clinical settings and requires joint efforts from multidisciplinary team (MDT). This review systematically updates the epidemiology, molecular pathogenesis, genomics/genetics study, diagnosis and treatment of ILD related to anti-lung cancer agents. By the integration of the latest evidences, the paper offers clinical work references for early diagnosis of ILD related to anti-lung cancer agents to enhance the survival and quality of life of the lung cancer patients.
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The application of small molecule targeted drugs for lung cancer has significantly improved the survival of lung cancer patients. However, these drugs have a wide variety of types, fast development and market launch of new drugs, complex adverse reactions, and are mostly used at home, which increases the risk of irrational drug use. At the same time, insufficient monitoring of efficacy and safety is also prone to occur, ultimately affecting treatment outcomes. This consensus focuses on 43 small molecule targeted drugs or combinations for lung cancer, providing standardized recommendations for rational drug use and monitoring of efficacy/adverse reactions in clinical practice. The recommendations are regarding drug selection, dosage adjustment, efficacy monitoring, adverse reaction monitoring, and improvement of patient compliance. This consensus aims to improve the rational use and efficacy/safety monitoring quality of small molecule targeted drugs for lung cancer, ensure the effectiveness and safety of drug treatment, prolong the survival of lung cancer patients and improve their quality of life.
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Peritoneal metastasis is a common form of distant metastasis in patients with colorectal cancer, and it is typically associated with a poor prognosis. The development of peritoneal metastasis involves complex molecular mechanisms and multifactorial regulation of the tumor microenvironment. Due to the presence of the blood-peritoneal barrier, only a small amount of systemic medication reaches the peritoneal cavity, resulting in limited efficacy against peritoneal metastasis. Intraperitoneal administration shows significant therapeutic advantages as it can directly target the tumor microenvironment, maintain high local drug concentrations, and reduce systemic toxicity. Intraperitoneal chemotherapy, especially hyperthermic intraperitoneal chemotherapy, has become a cornerstone therapeutic strategy in the clinical treatment of peritoneal metastasis. When selecting chemotherapy drugs and drug combinations, pharmacokinetic properties, efficacy, and safety must be comprehensively considered to optimize the treatment outcomes. In addition, the unique microenvironment of the peritoneal cavity provides new treatment approaches for biological treatment strategies, including antitoxins, vaccines, immune checkpoint inhibitors, etc. Techniques such as pressurized intraperitoneal aerosol chemotherapy and novel drug delivery systems demonstrate potential for enhanced efficacy, offering promising alternatives to improve patient outcomes. This article will review peritoneal barrier characteristics, intraperitoneal drug transport, intraperitoneal chemotherapy, and intraperitoneal biological therapies, thereby establishing a theoretical framework for precision therapy in colorectal cancer peritoneal metastasis.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an emerging therapeutic modality for peritoneal carcinomatosis. This review aims to evaluate the safety, efficacy, and current clinical application of PIPAC in the treatment of peritoneal metastases originating from gastrointestinal malignancies. This review outlines the technical principles, historical development, procedural steps, commonly used drugs, and administration protocols of PIPAC; analyses the current clinical application status of PIPAC technology; discusses the current challenges and future directions of PIPAC; suggests that PIPAC technology still needs to conduct more high-quality and large-sample clinical trials to further establish the safety and efficacy of PIPAC, optimize its indications and formulate standardized operation specifications. In the future, multi-centre cooperation, multi-disciplinary cooperation, precision medicine strategies and new drug research and development will promote the clinical transformation and standardized application of PIPAC technology.

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of advanced malignancies, but they can cause a wide range of adverse effects, including inflammatory arthritis. Severe ICI-induced inflammatory arthritis (ICI-IA) is rare, and its distinguishing clinical features are not defined. We present a patient with metastatic urothelial carcinoma who developed severe, polyarticular inflammatory arthritis while being treated with an ICI. Arthrocentesis of native and prosthetic joints revealed a significantly elevated white blood cell (WBC) count with a neutrophil predominance. Antibiotics were discontinued when the extensive infectious workup remained negative, and the patient was diagnosed with ICI-IA. This presentation of ICI-IA had overlapping features with septic arthritis, resulting in high diagnostic uncertainty. We comprehensively reviewed all published literature on the clinical features of severe ICI-IA. In the literature, synovial fluid findings revealed variable WBC counts but consistently have a neutrophil predominance. Although severe cases are rare, 9 previously reported cases shared similarities, including polyarticular presentation, elevated inflammatory markers, and absence of other rheumatic disease. Severe ICI-IA appears to have significant clinical overlap with culture-negative septic arthritis. This case report and literature review emphasize that ICI-IA should not be ruled out based on the presence of synovial fluid with elevated WBC with a neutrophil predominance. Early steroid use should be considered. Keywords: checkpoint inhibitor, inflammatory arthritis, immune-related adverse effects.