Inflammation is a hallmark of cancer, significantly contributing to tumor progression and therapeutic outcomes. Among the diverse cellular components of the tumor microenvironment, fibroblasts have been recognized as key regulators of inflammatory processes. Under tumor‑specific conditions, cancer‑associated fibroblasts (CAFs) undergo differentiation and promote tumor proliferation, metastasis and immune evasion via highly intricate mechanisms. This review provides a comprehensive analysis of the reciprocal interactions between CAFs and inflammation, elucidating the mechanisms by which CAFs induce pro‑inflammatory signaling and how inflammatory mediators, in turn, potentiate CAF activation and function. Furthermore, innovative therapeutic strategies, including the inhibition of stromal proteins, hypoxia‑inducible factor 1α and metabolic pathways associated with CAFs, as well as the application of nanoparticle‑based drug delivery systems, are examined for their potential to impede CAF‑mediated tumor progression. Pharmacological agents targeting CAF‑associated signaling pathways or inflammatory cytokines show dual efficacy by concurrently modulating inflammatory responses and CAF activity. These approaches frequently demonstrate improved therapeutic efficacy compared to interventions solely directed at CAF surface proteins, highlighting the therapeutic potential of concurrently addressing both inflammation and CAFs to enhance cancer treatment efficacy.

Immune checkpoint blockade therapy has revolutionized cancer treatment, yet its clinical efficacy remains limited to a subset of patients with specific tumor types. The present review provides a comprehensive analysis of T cell‑mediated antitumor immunity from both local and systemic perspectives, with particular emphasis on CD8+ T cells as primary effectors. The review discusses how the complex trafficking between the tumor microenvironment (TME), surrounding lymphoid tissues and peripheral circulation creates multiple opportunities for tumors to evade immune surveillance. Within the TME, T‑cell exclusion mechanisms, antigen specificity and the spectrum of T‑cell exhaustion states, from progenitor exhausted T cells to terminally exhausted T‑cell phenotypes, are reviewed. Beyond the local TME, the crucial roles of tumor‑draining lymph nodes and tertiary lymphoid structures in maintaining sustainable antitumor immunity, as well as the significance of circulating T cells as both biomarkers and therapeutic targets, are analyzed. This systemic perspective provides insights into the dynamic nature of antitumor immunity and suggests potential strategies for next‑generation immunotherapies, including combination approaches targeting multiple immune compartments to achieve optimal therapeutic outcomes.

The efficacy of regorafenib or fruquintinib in combination with PD-1/PD-L1 inhibitors for metastatic colorectal cancer (mCRC) treatment has not been elucidated. This study aims to systematically evaluate the efficacy and safety of this combination therapy.

Flavonoids and chalcones, widely recognised for their diverse biological activities, have garnered attention due to their potential therapeutic applications. This review discusses fluorinated flavonoids and chalcones, focusing on their prospective anti-inflammatory, antidiabetic, anticancer, antiosteoporotic, cardioprotective, neuroprotective, hepatoprotective, antimicrobial, and antiparasitic applications. The enhanced biological activities of fluorinated derivatives, particularly the antibacterial, antiviral, and anticancer properties, are attributed to the introduction of fluorine groups, which increase lipophilicity and metabolic stability. Key findings indicate that fluorinated flavonoids and chalcones exhibit synergistic effects with antibiotics, inhibit bacterial efflux pumps, and reveal potent antiviral and anticancer properties. However, challenges such as cytotoxicity and structural optimisation have to be addressed. The synthesis of fluorinated flavonoids and chalcones is discussed, with emphasis on various synthetic methods such as condensation and cyclisation reactions starting from fluorinated precursors, as well as fluorination strategies, including the use of molecular fluorine or fluorinating agents. Fluorinated flavonoids and chalcones represent candidates for therapeutic development and have the potential to overcome drug resistance. However, further studies are necessary to adjust their pharmacological profiles.

The use of plant extracts and the compounds isolated from them for the treatment of cancer is an area of active research, given their therapeutic potential. This work focused on evaluating the literature related to the antiproliferative activity of extracts obtained from plants of the genus Tabebuia and molecules isolated in vitro or in vivo. For the search, MeSH and DECS terms were employed in the PubMed, Scopus, and SciELO databases. Research has shown that plant extracts derived from plants of the genus Tabebuia exhibit potential applications in the search for new molecules with antiproliferative activity. Among the isolated molecules, the most evaluated correspond to β-lapachone (naphthoquinone); however, molecules with antiproliferative potential belonging to groups such as iridoids, flavonoids, quinones, furanonaphthoquinones, triterpenes, and polysaccharides have also been isolated and reported. Additionally, synthesized molecules have been evaluated on the basis of the modifications made to the structures of molecules isolated from the plant extracts to increase their activity, aiming to develop more potent antitumor agents for future clinical use.

Immunotherapy has significantly changed the treatment paradigm for solid tumors, with immune checkpoint inhibitors now established in the management of many malignancies. Despite initial success, durable responses remain limited to a subset of patients, often less than 30%, due to both intrinsic and acquired resistance mechanisms. These challenges have prompted the development of next-generation immunotherapies. Recent efforts have expanded the scope of immunotherapy beyond PD-1/PD-L1 and CTLA-4 inhibition, focusing on new immune targets currently under investigation in early phase clinical trials. These include novel immune checkpoint inhibitors, immunomodulators targeting the tumor microenvironment, and bispecific antibodies. This review provides a comprehensive overview of emerging immune targets currently being investigated in early drug development, discussing their mechanisms of action, preliminary clinical outcomes, and potential future directions.

Silver nanoparticles (AgNPs) have emerged as promising agents in cancer diagnostics and/or therapy, demonstrating a lot of possible pharmacological actions. However, understanding the pharmacokinetics and safety profiles of nanoparticles, which is crucial for their clinical application, still raises many questions. Studies indicate that AgNPs can accumulate in tumour tissues, improving drug delivery and specificity. However, their interaction with biological systems necessitates thorough safety evaluations. Classical methods for assessing AgNPs' safety include cytotoxicity assays, genotoxicity tests, and histopathological examinations. However, novel techniques are emerging, such as advanced imaging and biomarker analysis, offering more precise toxicity assessments. Prediction models, including computational simulations and in silico analyses, are being developed to forecast AgNPs' toxicity profiles. These models aim to reduce reliance on animal testing and expedite the evaluation process. To mitigate potential risks associated with nanoparticle-based therapies, strategies such as surface modification, controlled release systems, and targeted delivery are being explored. These methods aim to enhance therapeutic efficacy while minimizing adverse effects. The main aim of this review article is to describe AgNPs from the point of view of their pharmacokinetic/toxicokinetic profile in the light of modern knowledge. Special attention will be given to novel methods for assessing the safety and toxicity profiles of AgNPs, providing insights into their interactions with cancer therapies and their potential clinical applications.

Colon cancer is the second leading cause of cancer-related deaths in the world. This is commonly observed among older adults, and the occurrence of colon cancer is mainly influenced by unhealthy lifestyle factors. Edible medicinal mushrooms have been demonstrated to have anti-colon cancer effects both individually and in combination with conventional therapies, including synergistically enhancing the efficacy of chemotherapy medications such as 5-fluorouracil in preclinical models. Medicinal mushrooms such as Lentinus edodes, Phellinus linteus, Ganoderma lucidum, Inonotus obliquus, Pleurotus ostreatus, Hericium erinaceus, Pleurotus eryngii, Gloeostereum incarnatum, and Termitomyces heimii are emerging as promising candidates, not only because conventional treatments for colon cancer face significant limitations, including side effects, psychological impacts on patients, high cost, limited specificity toward cancer and healthy cells, and the development of drug resistance, but also due to the diverse array of bioactive compounds present within them. Therefore, there is a strong demand for innovative, affordable, and minimally invasive treatments such as medicinal mushrooms. Their bioactive compounds, including terpenoids, sterols, phenols, polysaccharides, acids, sesquiterpenes, alkaloids, lactones, metal-chelating agents, nucleotide analogs, glycoproteins, β-glucan, cerebrosides, steroids, terpenes, quinolones, anthraquinones, benzoic acid derivatives, linoleic acid, ascorbic acid, glycosides, organic acids, flavonoids, grifolin, tocopherols, proteins, indoles, lectin, and laccases, exert anti-colon cancer activities through various mechanisms, including anti-proliferative effects, cell cycle arrest, anti-inflammatory effects, antioxidant effects, induction of apoptosis, cytotoxic effects, and antimigratory effects. Further research is needed to elucidate the molecular mechanisms and confirm the safety and efficacy of medicinal mushrooms as a holistic anti-colon cancer treatment.

Otorhinolaryngological (ORL) cancers, including malignancies of the oral cavity, pharynx, and larynx, show significant challenges in oncology. Cisplatin, a platinum-based chemotherapy drug, remains a cornerstone of treatment but is often limited by systemic toxicity and resistance. A comprehensive literature review was conducted using recent studies and clinical trials focused on nanotechnology-based cisplatin delivery systems. The analysis covered various types of nanocarriers, their mechanisms, and advantages. Additionally, the limitations of nanotechnology-based cisplatin delivery systems were discussed. Findings indicate that lipid-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and extracellular vesicles have demonstrated improved drug targeting, bioavailability, and reduced systemic toxicity in preclinical and clinical studies. Nanocarriers also offer potential for overcoming drug resistance and enabling combination therapy. However, challenges related to biocompatibility, scalability, and regulatory approval remain significant barriers to widespread clinical adoption. Nanotechnology offers a novel and promising approach to optimizing cisplatin delivery for ORL cancers. While preclinical studies demonstrate significant potential, further research and clinical validation are essential to translate these advancements into routine clinical practice. Addressing manufacturing and regulatory challenges will be critical for future research.

Lysine acetyltransferase 8 (KAT8) is a member of the MYST family of histone acetyltransferases. It catalyzes the acetylation of histone H4 at lysine 16 (H4K16ac) and non-histone proteins. Abnormal upregulation or downregulation of KAT8 and its associated H4K16ac have been observed in malignant tumors, suggesting its close association with tumorigenesis and progression. Characterized by structural diversity and multi-target mechanisms, natural agents have been increasingly shown to possess significant antitumor activity. This review focuses on KAT8, summarizing its molecular mechanisms in regulating tumor development by catalyzing substrate protein acetylation, which impacts tumor cell proliferation, cell cycle regulation, apoptosis, DNA damage repair, and autophagy. It also systematically discusses the pharmacological activities and molecular mechanisms of small-molecule agents that target KAT8 to inhibit tumor proliferation, including natural compounds, synthetic drugs, and non-coding RNAs.

Aging is characterized by a progressive deterioration in physiological function and an increased susceptibility to age-related diseases, such as cancer. Monoclonal antibodies (mAbs) constitute a novel therapeutic approach aimed at addressing aging mechanisms such as cellular senescence, inflammaging, and immunosenescence. This text presents an overview of mAb methods aimed at the markers of aging and their potential application in cancer treatment. The mAbs can be categorized into senolytics, senescence-associated secretory phenotype (SASP) neutralizers, and immune checkpoint inhibitors, each targeting fewer aging-related pathways relevant to cancer therapeutic enhancement than the last. Translating promising preclinical evidence into enhanced efficacy and safety in cancer therapy presents challenges, particularly in older populations. This study examines the therapeutic efficacy of mAbs in the treatment of cancer and age-related disorders, focusing on their current and future roles in oncology practice.

In recent years, the incidence rate of cancer has been on the rise all over the world, and the age of cancer patients has shown a younger trend, which seriously endangers patients' health. Edible/medicinal mushrooms have not only become a new source of nutritional supplements but have also emerged as a promising adjunct to conventional medicine, either by directly or indirectly killing tumor cells and enhancing immunity, or through their use in conjunction with modern cancer therapies to enhance their efficacy or reduce their side-effects, improving patients' quality of life. Although the anti-cancer potential of edible and medicinal mushrooms has been widely studied in the past, this review focuses on the most recent literature from the last five years, providing an up-to-date and comprehensive summary of the current findings. In this review, we aim to analyze the anti-cancer effects of edible/medicinal mushrooms, including Schizophyllum commune, Trametes versicolor, Grifola frondosa, Ganoderma lucidum, Lentinula edodes, Laetiporus sulphureus, Boletus edulis, and Phellinus igniarius, as well as their potential anti-cancer mechanisms, providing strong theoretical support for the further development of edible/medicinal mushroom anti-cancer products.

Isorhamnetin (ISO) is a natural flavonoid compound that has become a main research topic in recent years due to its multitargeted antitumor properties. In this paper, we systematically review the molecular basis of the inhibition of malignant tumors by ISO, including through the regulation of the cell cycle, PI3K/AKT/mTOR pathway, MAPK pathway, apoptosis/autophagy-related pathways, and the tumor microenvironment. We also explore its synergistic effects with chemotherapy/targeted therapies and its potential for clinical translation. Experimental studies have shown that ISO can not only directly inhibit tumor proliferation by inducing tumor cell cycle arrest, mitochondria-dependent apoptosis, and endoplasmic reticulum stress, but also enhance antitumor immune responses by regulating the immune microenvironment. Pharmacokinetic studies have shown that novel delivery systems, such as nano-formulations, significantly enhance the bioavailability of ISO. Notably, ISO has demonstrated unique advantages in attenuating the nephrotoxicity of chemotherapeutic agents, protecting normal cells, and reversing tumor resistance. However, the optimal dosing regimen, dose-effect relationship, and cross-species applicability need to be further validated by large-scale preclinical animal experiments and clinical trials. This paper provides a theoretical basis for the development and application of ISO for the treatment of malignant tumors and highlights its potential value in animal models.

Cancer is a medical problem that has been difficult to overcome on a global scale. Owing to the sharing of single or multiple genes or regulatory modules, cancer treatment often faces severe challenges. The core of network pharmacology lies in constructing human disease gene regulation networks and multi-pharmacology network. With the continuous updating and iteration of new technologies, it is helpful for us to systematically understand the occurrence and development mechanism behind complex diseases and elucidate the pharmacological mechanisms from the perspective of biological network balance. This review aims to clarify the application of network pharmacology in exploring the pharmacological treatment mechanism of natural products, drug repositioning, and new technology combinations in the context of complex pathogenesis of cancer, so as to help realize the full potential of network pharmacology. Additionally, we discuss the future development of network pharmacology to guide clinical diagnosis and treatment.

For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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Immune checkpoint inhibitor (ICI) have demonstrated efficacy in treating various cancers by modulating the immune system, but this can lead to immune-related adverse events (irAEs), including myocarditis. ICI-associated myocarditis is a rare but highly lethal irAE with a short mean time to onset, and difficult to diagnose early due to nonspecific symptoms and lack of biomarkers. This review highlights the need for improved recognition and management of ICI-associated myocarditis, summarizing recent advances in immunology, pathology, and biomarker research. We discuss the epidemiology, clinical features, immunological mechanisms, and roles of biomarkers in diagnosis and risk stratification. Traditional biomarkers like cTnI and hs-cTnT are sensitive but lack specificity, while emerging biomarkers like miR-155 show tissue specificity. Inflammatory markers such as NLR and CRP aid prognosis but have limited diagnostic value.

Procyanidins (PCs), dietary polyphenols found in fruits, vegetables, and beverages, exhibit potent anticancer properties. Their mechanisms of action involve modulating oxidative stress, inhibiting angiogenesis, inducing apoptosis, and preventing tumor progression. Despite promising preclinical and clinical findings, their therapeutic potential remains underexplored. This review aims to provide a comprehensive analysis of the anticancer properties of PCs, including their bioavailability, pharmacokinetics, and safety. A systematic literature search was conducted across databases such as PubMed, Scopus, and Web of Science, utilizing Medical Subject Headings (MeSH) terms and specific keywords. Studies were selected based on predefined inclusion criteria, focusing on in vitro, in vivo, and clinical evidence. PCs demonstrate anticancer effects through multiple pathways, including inhibition of pro-inflammatory cytokines, suppression of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, and regulation of apoptosis-related proteins such as BCL2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and caspases. PCs demonstrate anticancer effects through multiple pathways, including inhibition of pro-inflammatory cytokines, suppression of the PI3K/AKT/mTOR and MAPK/ERK pathways, and regulation of apoptosis-related proteins such as BAX, BCL-2, and caspases. However, their low oral bioavailability and metabolic instability pose challenges for clinical application. Current research highlights the need for novel delivery systems, such as nanoparticles and liposomes, to enhance systemic absorption and therapeutic efficacy. Ongoing clinical trials are investigating the potential of PCs as adjuvants in cancer therapy, either alone or in combination with chemotherapeutic agents. Future studies should focus on optimizing their pharmacokinetics, exploring synergistic effects with existing treatments, and conducting large-scale clinical trials to validate their efficacy and safety. PCs hold promise as natural anticancer agents, with the potential to complement conventional therapies and improve patient outcomes.

Acute myeloid leukemia (AML) is marked by uncontrolled growth of malignant cells in the bone marrow, presenting a major challenge in hematology despite treatment advances. Curcumin, a polyphenol from turmeric, shows promise as an anticancer agent with multiple mechanisms targeting pathways like NF-κB, STAT3, PI3K/AKT, and MAPK. This review highlights curcumin's antileukemic effects, including apoptosis induction, cell proliferation inhibition, and angiogenesis modulation. Although low bioavailability limits its clinical use, nanoformulations such as liposomes and micelles have improved curcumin's stability and uptake. Combining curcumin with standard chemotherapies has shown synergistic effects, enhancing anticancer efficacy. Preclinical studies consistently demonstrate curcumin's antileukemic impact in AML cell lines and animal models, showing reduced tumor load and prolonged survival. Ongoing clinical trials are assessing curcumin's safety and efficacy in AML patients, with early results indicating potential. However, larger randomized trials are needed for confirmation. In conclusion, curcumin's anticancer properties and safety profile make it a valuable candidate for AML treatment. Further research is necessary to refine delivery methods, optimize combination therapies, and substantiate its role through clinical trials.

Tumorigenesis and metastasis of solid tumors are coupled to profound biophysical changes that alter cancer cells' mechanobiology, critically impacting metastatic progression. In particular, cell stiffness determines the ability of cancer cells to invade surrounding tissues, withstand shear fluid stress and evade immune surveillance. Here, we summarize the biological factors, pathological factors, and therapeutic modalities that affect the mechanobiology of cancer cells. We focus on clinically utilized chemotherapeutics and targeted therapies that show direct and indirect modulation of cancer cells' stiffness and discuss how these treatments can be used in combination with other treatment modalities to improve patient outcomes. Finally, we list the outstanding challenges in the field and provide a perspective on expanding the clinical utilization of experimental therapeutics that can act as "mechanotherapeutics" by regulating mechanobiology of cancer cells.

The Wnt/β-catenin signaling pathway is a highly conserved signaling pathway closely linked to cancer development through various biological processes, including oncogenic transformation, genomic instability, cancer cell proliferation, stemness, metabolism, cell death, immune regulation, and metastasis. Notably, its activation plays a crucial role in drug resistance to chemotherapy, targeted therapy and immunotherapy. Recent advances in drug development have identified several targeted inhibitors acting at key nodal points of this pathway, with some demonstrating synergistic efficacy when combined with immunotherapeutic agents. This review provides a comprehensive analysis of current understanding regarding the Wnt/β-catenin pathway in malignancy, emphasizing its multifaceted roles in tumor initiation, therapeutic resistance, and immune regulation. Additionally, we summarized the clinical performance of combination therapies targeting the Wnt/β-catenin pathway in conjunction with chemotherapy, targeted therapy, and immunotherapy. Although clinical development remains at a relatively early stage, pharmacological modulation of Wnt/β-catenin signaling offers considerable potential as a novel therapeutic paradigm in precision oncology.