This scoping review aimed to map the existing evidence on the associations between habitual food group intake and chemotherapy-induced toxicity and to identify critical gaps in the literature.

The role of microbes in cancer is gaining attention these days, especially in the context of tumor-associated biofilms and dysbiotic microbiota. Biofilm-producing microorganisms, such as Fusobacterium nucleatum and Helicobacter pylori, trigger oncogenic inflammation and immune evasion in tumor initiation and progression, and in the development of chemoresistance, through the activation of the NF-κB, STAT3, and β-catenin pathways. Dietary terpenoids are a structurally diverse group of antitumor and antibiofilm plant metabolites. Monoterpenoids, sesquiterpenoids, and triterpenoids are known to inhibit quorum sensing, the biosynthesis of extracellular polymeric substances (EPS), and the expression of biofilm-associated virulence factors, proposing an unexplored convergence among antibiofilm and anticancer mechanisms. Importantly, the biofilm structure (thickness, developmental stage, EPS density) affects the efficacy of terpenoids, affecting diffusion, microbial persistence, and therapeutic susceptibility. The quorum-sensing disruption is more effective in the early stages of biofilms, while high concentrations of EPS in mature, thick biofilms will require more penetration to disrupt quorum sensing. Innovative functional food matrices, including nano-enabled delivery systems, are emerging strategies to improve bioavailability and microbiome modulation of terpenoids. Furthermore, nano-formulations allow better penetration in dense biofilm matrices, protect terpenoids from early degradation, and allow prolonged and focused drug release in the tumor microenvironment associated with biofilms. Combining precision nutrition with microbiome-informed dietary strategies can be used to prevent and treat cancer. The present review combines studies linking biofilm-driven carcinogenesis with terpenoid-mediated antibiofilm-anticancer pathways and nano-mediated functional delivery and biofilm penetration, including highlighting the potential for microbiome modulation in cancer therapy.

Immune checkpoint inhibitor (ICI)-related overlap syndrome involving myositis, myocarditis, and myasthenia gravis (3M overlap syndrome) is rare but potentially fatal. Current evidence is derived mainly from case reports and small case series, and individual case-level data on ancillary diagnostic findings, baseline comorbidities, treatment patterns, and short-term outcomes remain limited.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) have transformed precision oncology by exploiting synthetic lethality in homologous recombination (HR)-deficient cancers, with multiple FDA-approved agents targeting BRCA1/2-mutant tumors. Despite initial efficacy, resistance inevitably emerges, limiting long-term clinical benefit. This review synthesizes emerging mechanistic insights into PARPi response and resistance. Recent evidence reframes PARP inhibition cytotoxicity through a transcription-replication conflict model and identifies single-stranded DNA gaps as the primary lethal lesion in HR-deficient cells, rather than double-strand breaks. These findings suggest that resistance reflects restoration of replication gap suppression or resolution of transcription-replication stress. We further highlight DNA ligase III as a collateral vulnerability in 53BP1-deficient resistant tumors, and discuss proteolysis-targeting chimera (PROTAC)-based PARP1 degraders as a strategy to overcome resistance and induce alternative cell death pathways. Established resistance mechanisms-including BRCA1/2 reversion mutations, shieldin complex loss, RAD51 hyperactivation, and pharmacokinetic alterations-are reconsidered within this updated framework. Combination strategies with ATR inhibitors show promising clinical activity in PARPi-resistant HR-deficient ovarian cancer. Finally, we propose an integrated biomarker framework combining HRD scar assays, functional RAD51 foci analysis, replication gap profiling, and circulating tumor DNA (ctDNA) monitoring to enable dynamic resistance tracking.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Approximately 15% of localized and 5% of metastatic cases exhibit mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). While immune checkpoint inhibitors (ICIs) have revolutionized the first-line treatment for this subgroup, 15%-46% of patients experience primary resistance, and a subset of responders eventually acquires resistance. This review synthesizes the multifaceted mechanisms underlying ICI resistance in dMMR/MSI-H CRC. We delineate tumor-intrinsic alterations, including defects in the antigen presentation machinery (specifically transporter associated with antigen processing [TAP]1/TAP2 and β2-microglobulin [β2m]), oncogenic signaling via the Wnt/β-catenin and JAK/STAT pathways, and epigenetic remodeling involving ARID1A. Furthermore, we explore the role of the immunosuppressive tumor microenvironment (TME), characterized by T-cell exclusion and myeloid-derived suppressor cell (MDSC) accumulation. To address these barriers, we evaluate the clinical potential of third-generation ICIs targeting lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and TIGIT, as well as emerging biomarker strategies such as gut microbiome modulation and circulating tumor DNA (ctDNA) dynamics. By integrating these mechanistic insights with novel therapeutic approaches, including bispecific antibodies (BsAbs) and adoptive cell transfer, this review aims to provide a roadmap for overcoming resistance and advancing precision immunotherapy in dMMR/MSI-H CRC.

RNA-binding proteins (RBPs) remain underexplored as small-molecule targets, although their dysregulation contributes to numerous human diseases, including cancer. RBPs are key regulators of post-transcriptional gene expression, controlling multiple stages of RNA metabolism. Among them, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is an oncofetal RBP that is highly expressed during embryonic development, largely absent in adult tissues, and re-expressed in multiple malignancies. A growing body of evidence supports IGF2BP3 as a diagnostic and prognostic biomarker and a potent oncogenic driver across tumor types, underscoring its potential as a therapeutic target. However, the development of effective IGF2BP3-targeting compounds remains in its early stages. In this review, we first describe the structural organization of IGF2BP3, the molecular basis of RNA recognition, and the mechanisms underlying its dysregulation across human cancers. We then discuss emerging therapeutic approaches, including direct inhibition of IGF2BP3-RNA interactions and indirect strategies that rewire IGF2BP3 expression or activity through epigenetic, epitranscriptomic, and signaling pathways. By critically highlighting the opportunities and limitations of these approaches and their impact on cancer progression, we provide an integrated perspective combining structural biology, medicinal chemistry, and cancer biology to support the development of next-generation IGF2BP3-targeted therapies.

UDP-glucuronosyltransferases (UGTs) are a key family of phase II metabolic enzymes in humans that play a central role in maintenance of metabolic homeostasis and drug disposition by catalyzing glucuronidation of endogenous and exogenous substances. UGT-mediated metabolism of antitumor drugs plays a dual role in tumor drug resistance, emerging as a hotspot in cancer therapy. This review outlines the structural characteristics, classification system, tissue distribution, and multilevel regulation of UGTs, with a focus on their bidirectional roles in tumor drug resistance, i.e., promotion of resistance through metabolic clearance and inhibition of resistance through metabolic activation. This review also discusses strategies of multidimensional tumor resistance intervention based on UGTs, and we also discussed the challenges in the clinical translation of current UGT-targeting strategies. To date, most data on UGTs were derived from in vitro and preclinical models; clinical validation remains limited, and the dual roles of UGTs are highly context-dependent. This review article provides a perspective for comprehensive understanding of UGT-mediated tumor resistance and offers theoretical foundations and practical directions for development of novel antitumor strategies.

Cancer stem cells (CSCs) drive therapeutic resistance, metastasis, and tumor recurrence through reversible transitions among stem-like, differentiated, epithelial, and mesenchymal states, which are sustained by interconnected epigenetic mechanisms. To our knowledge, this is the first review to integrate curcumin-mediated regulation of DNA methylation, chromatin remodeling, and non-coding RNAs within a single CSC plasticity framework and to propose the concept of an "epigenetic collapse of CSC plasticity" as a mechanistic explanation for how curcumin may weaken stemness, state switching, and adaptive treatment resistance. Evidence was critically evaluated through structured searches of PubMed/MEDLINE, Scopus, Web of Science Core Collection, Google Scholar, and citation tracking, while direct curcumin-epigenetic evidence was distinguished from independent CSC evidence and inferential mechanistic links. Curcumin has been reported to modulate DNMT1 and locus-specific DNA methylation; regulate HDACs, p300/CBP, EZH2, H3K27me3, and BMI1; and alter selected microRNA, long non-coding RNA, and circular RNA pathways, with comparatively stronger evidence involving the miR-34 family, miR-200c, miR-21, H19, and circHN1. However, current evidence is constrained by the predominance of bulk cancer-cell models, heterogeneous formulations and exposure conditions, and the scarcity of epigenetic rescue experiments combined with rigorous functional CSC assays. By unifying previously fragmented epigenetic evidence, this review advances a new evidence-weighted model in which curcumin may suppress CSC persistence not through a single molecular target, but by destabilizing the multilayer epigenetic circuitry that enables plasticity. Curcumin should therefore be regarded as a context-dependent, multilayer epigenetic modulator rather than an established CSC-eradicating therapy, and its translational relevance requires validation in prospectively defined CSC models with pharmacologically justified delivery and exposure conditions.

Poly(ADP-ribose) polymerase inhibitors (PARPis) have demonstrated remarkable efficacy in tumors carrying BRCA1/2 pathogenic variants (PVs) through the mechanism of synthetic lethality. PVs in other homologous recombination (HR) genes may also impair homologous recombination repair and confer sensitivity to PARPis; however, their predictive value remains uncertain and appears to vary according to the affected gene and tumor type. We review and critically discuss the current evidence regarding the predictive value of non-BRCA HR gene pathogenic variants as biomarkers of PARPi sensitivity across ovarian, breast, prostate, and pancreatic cancers. A narrative review was conducted between October 2023 and December 2025, first identifying pivotal clinical trials of PARP inhibitors across ovarian, breast, prostate, and pancreatic cancers, followed by a targeted search of PubMed, Embase, Web of Science, and Google Scholar for relevant preclinical and clinical studies. Seventeen clinical studies and multiple preclinical reports were analyzed regarding genomic frequency, HRD association, and treatment response. Preclinical studies consistently demonstrated increased PARPi sensitivity in models with alterations in several non-BRCA HR genes. Clinical evidence, however, was heterogeneous. PALB2 demonstrated the strongest and most consistent association with PARPi benefit across tumor types, while RAD51C and RAD51D also showed clinically meaningful activity, particularly in ovarian cancer. In contrast, evidence supporting PARPi sensitivity in tumors harboring ATM, CHEK2, CDK12, and several other HR gene alterations remained limited or inconsistent. Differences in gene function, biallelic inactivation, variant type, and current limitations of HRD companion diagnostic assays likely contribute to the observed variability in clinical response. Non-BRCA HR gene alterations represent promising predictive biomarkers for PARPi therapy but should not be considered a homogeneous group. Future biomarker-driven studies integrating comprehensive genomic profiling and functional assessment of homologous recombination deficiency are needed to refine patient selection and optimize the clinical application of PARPis beyond BRCA1/2-associated cancers.

This review provides an updated and comprehensive assessment of the current literature on quinoa (Chenopodium quinoa Willd.) saponins, with particular emphasis on pharmacological effects. Quinoa (Chenopodium quinoa Willd.) is an annual plant native to South America. Quinoa seeds are characterized by high nutritional value and are rich in proteins, lipids, carbohydrates, minerals, and saponins. Saponins are found in quinoa seeds and impart a bitter taste, which is why they are typically removed before seed consumption. Saponins have been characterized as antinutritional agents, but in recent years they have been investigated for their pharmaceutical applications. Protocols have been developed for the extraction of saponins from seeds, such as conventional solid-liquid extraction (maceration), ultrasound-assisted extraction, microwave-assisted extraction, enzyme-assisted extraction, and pressurized liquid extraction. Ultrasound-assisted extraction and microwave-assisted extraction are considered the most suitable methods for quinoa saponins. Quinoa saponins have shown promise as vaccine adjuvants. Furthermore, they have demonstrated direct anticancer activity, inducing apoptosis and inhibiting the proliferation of breast and colon cancer cells. In general, saponins can induce hemolysis at high concentrations through membrane disruption, primarily via lipid solubilization or pore formation. However, hemolytic activity varies significantly among different saponins and depends on their chemical structure and concentration. In vivo, they have not recorded adverse side effects at doses below 50 mg/kg body weight per day. More than 40 triterpenoid saponins, mainly derived from oleanolic acid, ederagenin, phytolaccagenic acid, and sergianic acid, have been identified in quinoa. Overall, although quinoa saponins have traditionally been considered antinutritional compounds, accumulating evidence indicates that they possess promising pharmacological properties, particularly as anticancer agents.

Melanoma is a malignant tumor that originates in pigment-producing cells called melanocytes. This type of cancer remains a major public health challenge due to its high metastatic potential and resistance to treatment. Autophagy is a catabolic process that enables the controlled degradation of damaged cellular organelles and unnecessary or abnormal macromolecules. Its primary function is to maintain intracellular homeostasis and cell survival. There are three main types of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). The role of autophagy in oncogenesis is multifaceted and context-dependent-depending on the type of cancer and its stage of development. Autophagy can either promote tumor progression or act as a tumor-suppressive mechanism. Factors influencing the role of autophagy in cancer include inflammation, crosstalk with apoptosis and resistance to anticancer therapies. Current research is focused on the use of both autophagy inhibitors and autophagy inducers as potential strategies to improve the effectiveness of melanoma treatment.

The review covers research on dual-target antitumor agents over the past five years. One of the targets is histone deacetylases (HDACs), while the second potential target is a protein group located both on the membrane surface (phosphatidylinositol 3-kinase (PI3K), anaplastic lymphoma kinase (ALK), receptor tyrosine kinase (AXL), tyrosine protein kinase (HER2), FMS-like tyrosine kinase (FLT3), and vascular endothelial growth factor receptor (VEGFR2)) and in the nucleus (serine/threonine protein kinase Wee1, DNA methyltransferase (DNMT), dual-specificity phosphatase (CDC25A), an enzyme from the cyclin-dependent kinase family (CDK9), dual-specificity tyrosine-serine/threonine kinase (DYRK2), and BET family proteins (BRD4, BD1, and BD2)). This review presents the results of studies on the inhibitory activity of various HDAC isoforms and other enzymes, as well as in vitro cytotoxicity studies on both neoplastic and healthy cells. It also includes selectivity studies, in vivo experiments (changes in tumor volume in mice) and oral bioavailability assessments. The review also describes the chemical structures of several dual-target agents and identifies the molecular fragments responsible for inhibiting different targets. Based on the studies reviewed in this paper, it can be concluded that some dual inhibitors have superior in vitro cytotoxicity and exhibit selectivity towards some tumor cells compared to monofunctional reference compounds. These findings may be useful for molecular design in the field of polypharmacology, with the aim of developing new dual-target molecules that exhibit improved antitumor activity and selectivity towards neoplastic cells.

Small-molecule kinase inhibitors offer a compelling therapeutic strategy for glioblastoma, yet their clinical efficacy remains severely limited by blood-brain barrier penetration and active efflux transporter extrusion. This review evaluates current medicinal chemistry approaches and translational paradigms to overcome these drug delivery and biological constraints. A critical analysis of the literature reveals that direct structural optimization faces a multidimensional balancing act; next-generation design must prioritize macrocyclization, structural rigidification, and bioisosteric capping to lower polar surface area and evade P-glycoprotein and BCRP efflux. Furthermore, carrier-mediated prodrugs targeting the LAT1 transporter provide a viable rescue strategy for highly potent scaffolds. Reviewing recent clinical failures, such as paxalisib and osimertinib, underscores that single-node monotherapies fail due to compensatory pathway hyperactivation and clonal heterogeneity, whereas multi-targeted agents or rational dual-node combinations prevent rapid tumor adaptation. Additionally, combining kinase inhibitors with DNA damage repair inhibitors, immune checkpoint modulation, or MR-guided focused ultrasound could provide powerful synergistic networks. Finally, bridging the translational gap requires complementing conventional serum-cultured cell lines with patient-derived glioma stem cells and orthotopic xenografts to better recapitulate the cellular architecture of the disease. Ultimately, overcoming the therapeutic challenges in glioblastoma demands a fundamental pivot toward rigorous neuro-pharmacological design and multi-lineage network oncology.

This review covers published data (mostly from 2019 to 2025) on the synthesis and biological activity of azolo[a]quinoxalines, including pyrazolo-, imidazo- and triazolo-annelated systems. We highlight that most research efforts are directed toward the design of anticancer agents, with additional applications as Toll-like receptor antagonists, monoamine oxidase inhibitors, opioid receptor modulators, PI3Kα inhibitors, tubulin polymerization inhibitors, GABAᴀ receptor modulators, VEGFR-2 kinase inhibitors, BRD9 binders, and anti-inflammatory, antimicrobial, and antifungal agents. Recent synthetic strategies include Cu-catalyzed oxidative annulations, I2-mediated C-H functionalization, metal-free cascade cyclization, and multicomponent reactions, often employing eco-friendly catalysts and reductants. A growing number of studies integrate virtual screening, molecular docking, and pharmacophore-based in silico approaches to guide lead discovery and optimization. Innovative drug delivery systems, such as nanogels and hybrid molecules combining azoloquinoxalines with pharmacophores like thalidomide, have also been explored. This review emphasizes both the medicinal chemistry aspects of azolo[a]quinoxalines and the synthetic methodologies for their preparation from the perspective of drug development and discovery.

While anti-tumor drugs markedly improve patient survival, dose-limiting toxicities remain major constraints on clinical efficacy and quality of life. Conventional management strategies lack timeliness and precision. Traditional Chinese medicine (TCM) and its active ingredients offer unique potential for mitigating anti-tumor drug toxicities through multi-component and multi-target regulation. However, the transformation of TCM is hampered by poor bioavailability and targeting. This review summarizes and evaluates an integrated strategy combining TCM with nanotechnology to develop novel nanomedicines. It elucidates the distinct toxicity mechanisms of chemotherapy drugs, targeted drugs, and immunotherapy drugs, revealing toxicopathological transitions from non-specific killing to microenvironment disruption and immune imbalance. Subsequently, it discusses the intervention mechanisms and research progress of TCM and its active ingredients targeting different categories of anti-tumor drug toxicity. To overcome delivery challenges, this review explores construction strategies for diverse nanodelivery systems, including carrier-free self-assembled nanomedicines, physically loaded nanomedicines, and chemically coupled nanomedicines, highlighting their value in organ-specific accumulation and controlled release. Finally, it objectively analyzes challenges in the clinical translation of these nanomedicines, encompassing safety and industrialization, while prospecting future trends, aiming to contribute to a new therapeutic paradigm focused on "toxicity attenuation and efficacy potentiation" and steer cancer treatment toward greater precision and intelligence.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide and represents the hepatic manifestation of a systemic cardiometabolic-inflammatory syndrome rather than an isolated organ disease. In parallel, anticancer therapies carry a well-recognised burden of cancer therapy-related cardiovascular toxicity (CTR-CVT). Evidence suggests that the metabolic-inflammatory cascade driving steatosis → steatohepatitis → fibrosis may also contribute to endothelial dysfunction, myocardial remodelling and cardiomyocyte vulnerability to chemotherapy-induced oxidative stress. This narrative review proposes a unifying conceptual framework in which MASLD may act as a potential amplifier of cardiotoxicity in oncology patients and examines whether lifestyle and dietary interventions could mitigate this cumulative risk. Methods: A structured literature search of PubMed, Scopus and Web of Science was performed, prioritising systematic reviews, meta-analyses, randomised controlled trials, large cohort studies and recent international guidelines on MASLD, cardio-oncology and nutritional interventions. Results: Four converging molecular axes were identified as plausible links between MASLD and cardiomyocyte susceptibility to anticancer therapy: mitochondrial dysfunction with reactive oxygen species overproduction, NLRP3 inflammasome activation and metaflammation, endothelial nitric oxide impairment, and pro-fibrotic TGF-β/hepatic stellate cell signalling. Mediterranean-style dietary patterns, selected micronutrients and emerging metabolic therapies modulate the same network and may offer translational opportunities. Conclusions: Reframing MASLD as a potentially modifiable amplifier of CTR-CVT supports the integration of hepatic phenotyping into baseline cardio-oncology risk stratification and the use of personalised nutrition as a precision tool acting on shared mitochondrial, inflammatory, endothelial and fibrotic pathways. Multidisciplinary framework and prospective interventional studies, adopting composite hepato-cardio-oncological endpoints, are warranted.

Wood-inhabiting fungi constitute a valuable source of biologically active compounds with significant therapeutic potential. Particular attention is paid to species known for their high content of polysaccharides, triterpenoids, phenolic compounds, and other secondary metabolites exhibiting cytotoxic and immunomodulatory activities. The results indicate that extracts obtained from these fungi may inhibit tumor growth, induce apoptosis, and support the immune response of the organism. Although further clinical studies are required, wood-inhabiting medicinal fungi represent a promising direction in the development of natural anticancer therapies and complementary treatment strategies.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Tumor angiogenesis plays a crucial role in breast cancer progression, making angiogenesis-associated pathways attractive therapeutic targets. Computational drug discovery approaches, including virtual high-throughput screening (VHTS), molecular docking, molecular dynamics simulations, and binding free energy calculations, have emerged as valuable tools for identifying and optimizing anticancer compounds. This review evaluates the application of these computational techniques in the discovery of antiangiogenic therapeutic candidates for breast cancer.

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that plays a central role in regulating cell growth, differentiation, and survival. In non-small cell lung cancer (NSCLC) and several other malignancies, activating mutations within the EGFR kinase domain lead to persistent receptor activation and uncontrolled downstream signalling. Over the past two decades, X-ray crystallographic studies and structural data deposited in the Protein Data Bank have significantly enhanced our understanding of EGFR activation mechanisms, mutation-driven conformational changes, and inhibitor binding interactions. This review provides a critical evaluation of structural insights obtained from crystal structures of wild-type and mutant EGFR, with particular focus on clinically important mutations such as L858R, T790M, and C797S. These mutations induce specific alterations in activation loop positioning, αC-helix orientation, and ATP-binding pocket architecture, thereby influencing drug binding affinity and therapeutic response. The structural basis for the evolution of EGFR tyrosine kinase inhibitors-from first-generation reversible inhibitors to mutant-selective covalent agents-is discussed in relation to emerging resistance mechanisms. Although structural characterisation has substantially contributed to rational drug design, the ongoing development of resistance mutations highlights the need to integrate crystallographic data with tumour biology and resistance pathways to achieve more durable therapeutic strategies.

The ubiquitin-proteasome system (UPS) plays a central role in regulating protein homeostasis and degradation. Its dysregulation is closely associated with various diseases, including cancer. S-phase kinase-associated protein 2 (SKP2) is a key E3 ubiquitin ligase component of the UPS. It induces proteasome-mediated protein degradation or modulates substrate function by conjugating K48-linked or K63-linked ubiquitin chains to diverse target proteins. Recent studies have shown that the overexpression of SKP2 in several cancer types is correlated with poor clinical outcomes, underscoring its potential as a therapeutic target. Notably, emerging evidence has expanded the functional repertoire of SKP2 beyond cell cycle control to encompass metabolism, DNA repair, stemness, tumor microenvironment (TME) and immunotherapy response, positioning it as an increasingly attractive target for intervention. In this review, the oncogenic properties of SKP2 and its underlying mechanisms were elucidated in multiple cancer types. Moreover, we systematically summarized future directions for SKP2-targeted therapy.