In light of searching for new breast cancer therapies, DNA-targeted small molecules were rationally designed to simultaneously bind DNA and inhibit human dihydrofolate reductase (hDHFR). Fourteen new arylidene-hydrazinyl-1,3-thiazoles (5-18) were synthesised and their dual DNA groove binding potential and in vitro hDHFR inhibition were performed. Two compounds, 5 and 11, proved their dual efficacy. Molecular docking and molecular dynamics simulations were performed for those active derivatives to explore their mode of binding and stability of interactions inside DHFR active site. Anti-breast cancer activity was assessed for 5 and 11 on MCF-7 cells using MTX as reference. IC50 measurements revealed that both compounds were more potent and selective than MTX. Cytotoxicity was examined against normal skin fibroblasts to examine safety and selectivity Moreover, mechanistic studies including apoptosis induction and wound healing were performed. Further in silico ADMET assessment was conducted to determine their eligibility as drug leads suitable for future optimisation and development.

Cancer and cardiovascular diseases (CVDs) are global health challenges. In cancer patients, CVD is the second leading cause of death following disease progression. There are few specialized services for cardio-oncology patients worldwide currently. Branched-chain amino acids (BCAAs) are essential amino acids that promote protein synthesis and energy homeostasis. The disruption of BCAAs metabolism facilitates the development of cancer and CVDs while the benefit of BCAA supplement is full of controversy. In this review, we summarized BCAA-related studies in cardiometabolism, cancer and chemotherapy-induced cardiotoxicity, and provided our perspectives on the roles of BCAAs in cardio-oncology. We find that supplementation of BCAAs presents protective effects in cardiometabolic diseases, while the influence on cancer is intricate and varies across different types of cancers. Large-scale clinical studies are needed to understand the long-term effects of BCAA intake and its impact on different stages of the disease. BCAAs have potential to mitigate chemotherapy-induced cardiotoxicity. Continued research is still essential to understand the precise mechanisms, determine optimal dosage and timing, and assess the effectiveness of BCAA supplement in cardio-oncology, in particular clinical research.

Breast cancer (BC) remains one of the significant health issues across the globe, being diagnosed in millions of women worldwide annually. Conventional therapeutic options have substantial adverse effects due to their non-specificity and limited drug bioavailability. Niosomes, being novel drug delivery systems formed from non-ionic surfactants, with or without cholesterol and charge-inducing agents, are used as therapeutic options in treating BC. Their formulation by various methods enhances the therapeutic efficacy and bioavailability and minimises side effects. Niosomal formulation of tamoxifen exhibits target drug delivery with enhanced stability, whereas docetaxel and methotrexate show sustained and controlled drug release, respectively. 5-Fluorouracil, doxorubicin, paclitaxel, cyclophosphamide and epirubicin show improved cytotoxic effects against BC when combined with other agents. Furthermore, repurposed niosomal formulations of anti-cancer drugs show improved penetration, reduced tumour volume and significantly enhanced anti-tumour effect. This review article focuses on the composition of niosomes and their application in BC treatment and then examines how niosomes could contribute to BC research.

This study aims to design and develop novel and efficient anti-hypoxic cell tumor drugs. Using the TH-302 as lead compound, structural modifications are conducted to synthesize a series of novel derivatives to investigate the structural activity relationship (SAR) against ovarian cancer cell line (SKOV3) and glioblastoma cell line (U87MG) in vitro. The structural modifications mainly include four aspects: changes in substituents on N; changes in isomers; changes in nitro group position; changes in substituting halogens in phosphoramide mustard. The results of CCK-8 assay indicate that the steric hindrance and electronic effects of substituents on N have significant impacts on the activity, while changes in nitro group positions have minimal effects on the activity, and Bromo-phosphoramide mustard exhibits better activity than Chloro-phosphoramide mustard. Compounds 15c and 16d exhibit significantly superior antitumor activity compared to TH-302, with IC50 values of 42 μM and 32 μM for SKOV3 cells, and IC50 values of 47 μM and 41 μM for U87MG cells, respectively.

The pursuit of highly effective and selective anticancer drugs remains a critical challenge. Metal-based complexes, particularly gallium-containing compounds, offer promising therapeutic avenues due to their unique mechanisms of action. To identify novel scaffolds for such complexes, we performed a comprehensive genomic analysis of Nocardia species, revealing the prevalence of siderophore biosynthetic gene clusters, including the highly conserved nocobactin NA-like clusters. From N. coubleae DSM 44960, we isolated three new siderophores, coublibactins A-C (1-3), along with eight congeners (4-11) with known planar structures, all characterized by exceptional iron-binding affinity. Subsequent gallium substitution yielded gallium complexes (Ga-1-11). Among these, Ga-6 exhibited significant anticancer activity against human acute promyelocytic leukemia NB4 cells with IC50 value of 1.35 μM. Pharmacological studies showed that Ga-6 induces cell cycle arrest and apoptosis in NB4 cells. Our findings revealed microbial siderophores as promising scaffolds for the design of next-generation metal-based anticancer therapeutics, particularly gallium-based agents.

Nanozyme-based electrochemical biosensors have emerged as an alternative to enzyme-based biosensors for next-generation bioanalysis. However, potential antibody modifications limit the catalytic sites of the nanozyme, thereby reducing sensor sensitivity. Here, a sensitive method for determining carcinoembryonic antigen (CEA) was developed. It involved coupling a cascade enzyme - enzyme - like catalytic reaction using Fe - Co Prussian blue analog nanozymes with high peroxidase - like activity (79.42 U mg-1). Briefly, the transduction of biological signals to chemical signals was achieved through the strategy centered on catalytic electroactive probes. Thereafter, with the assistance of the microelectrochemical workstation, the output of signals was realized. The platform exhibited an ultra-wide range of 0.020-100 ng mL-1 and a detection limit of 0.013 ng mL-1 CEA, which was mainly attributed to the excellent peroxidase activity, good conductivity, and synergistic amplification of current signals of synthesized nanozymes. In addition, the modification-free features greatly reduced the complexity of the bioassay and significantly improves its portability and cost-effectiveness. Overall, this study advances the development of nanozymes and their electrochemical biosensing applications and is expected to extend to the development of miniaturized devices in direct detection environments.

Breast cancer continues to be a major cause of death among women globally, with triple-negative breast cancer (TNBC) presenting a particularly difficult challenge due to its aggressive behaviour and the lack of effective treatment options. Nanotechnology, particularly the use of silver nanoparticles (AgNPs), has emerged as a promising avenue in oncological research. This review explores into the escalating field of green synthesis of nanoparticles, emphasizing sustainable approaches utilizing plant-based resources. Critical factors influencing nanoparticle synthesis, including reaction conditions, precursor types, and plant phytochemicals, are explored alongside advanced characterization techniques essential for evaluating nanoparticle properties. Special focus is given to the phytofabrication of silver nanoparticles and their multifaceted roles in breast cancer treatment, with detailed insights into their mechanisms, such as inducing apoptosis, generating reactive oxygen species (ROS), and disrupting mitochondrial function, particularly in TNBC cells. The review further highlights the advantages of plant-derived AgNPs, such as biocompatibility and reduced toxicity, while addressing challenges like scalability, reproducibility, and regulatory hurdles. Concluding with future prospects, this paper reflects the potential of green-synthesized AgNPs as a keystone in next-generation cancer therapeutics, paving the way for innovative and eco-friendly approaches in oncology.

The current study used an experimental model of mammary gland carcinoma to assess the chemo-sensitizing effectiveness of the combined administration of diacerein and 5-Fluorouracil (5-FU). With docking scores of -8.1, -7.6, and -9.2 kcal/mol, respectively, the molecular docking experiments showed that diacerein exhibits significant binding affinities to Caspase-3, NF-κB, and AKT1. Molecular dynamics Simulations revealed that diacerein has favourable binding free energy (ΔGbind) of -26.7 kcal/mol for Caspase-3, -24.2 kcal/mol for NF-κB, and -39.9 kcal/mol for AKT1, combined with low root mean square deviation (RMSD) values of 3.1 Å, 1.6 Å, and 2.1 Å for the three targets respectively. To validate these findings in vivo, Ehrlich solid tumor (EST) was induced in female Swiss mice. Four groups of animals were randomly assigned: EST + vehicle, EST + 5-FU, EST + diacerein, and EST + combination. Diacerein and 5-FU combination treatment increased EST mice's life span and reduced the solid tumor's weight and volume. Furthermore, diacerein and 5-FU combination significantly suppressed oxidative stress, inhibited AKT phosphorylation, decreased downstream inflammation (NF-κB, TNF-α, IL-1β), and increased apoptosis by modulating Bax, Bcl2, P53, and caspase-3 levels in tumor tissues. In conclusion, by inhibiting the AKT/NF-κB axis, diacerein and 5-FU combination showed possible antiproliferative effectiveness in the EST model.

Capsaicin (CAPS), a bioactive alkaloid derived from chili peppers, has garnered significant interest for its potential role as a combinatorial and chemosensitizing agent in cancer therapy. Numerous preclinical studies have demonstrated that CAPS enhanced the efficacy of various anticancer agents by promoting apoptosis, modulating autophagy and inhibiting angiogenesis, tumor growth, and metastasis. Additionally, CAPS modulated critical regulators of chemoresistance, such as P-glycoprotein (P-gp), extracellular signal-regulated kinase (ERK), nuclear factor-kappa B (NF-κB) pathway, and signal transducer and activator of transcription 3 (STAT3) pathway, thereby contributing to the reversal of multidrug resistance (MDR). Moreover, when administered in combination with chemotherapeutic agents, CAPS has been shown to improve treatment efficacy at lower drug concentrations. Given its multitargeted mechanism of action, CAPS represents a promising adjunct to conventional cancer therapies. However, due to its lipophilic nature, the development of optimized formulation strategies is essential to enhance its bioavailability and ensure consistent therapeutic outcomes. In conclusion, CAPS holds significant potential as a combinatorial and chemosensitizing agent, helping to overcome chemoresistance and enhance treatment outcomes across various malignancies. These promising findings warrant further preclinical and clinical investigations.

As part of efforts to identify natural modulators of multi-drug-resistant breast cancer, Euphorbia mauritanica L. chloroform extract yielded four undescribed oxygenated diterpenes, including three nor-ent-abietanes, euphomauritanol C-E (1-3), and one polyacylated jatrophane, euphomauritanolide A (4), along with two knowns, helioscopinolide A (5) and enukokurin (6). The chemical structures and configurations of compounds were established by combination of HRMS, FTIR, and NMR spectroscopic tools along with experimental and calculated TDDFT-ECD. The cytotoxicity evaluation of isolated compounds against the MCF-7ADR revealed 4 and 2 are the most potent with IC50 values of 3.2 ± 0.58 and 4.67 ± 0.29 μM, respectively. Co-administration of compounds 4 and 2 with DOX improved its cytotoxic effect, with a combination index value of 0.41 for 4, indicating a synergistic effect. Mechanistically, 4 modulated DOX anticancer properties via potentiating DOX-induced Go/G1 cell cycle arrest rather than G2M arrest of DOX alone and shifting the cell death of DOX to be mainly apoptotic cell death. Furthermore, 4 alone and combined with DOX showed promising anti-migratory effects against MCF-7ADR. In conclusion, 4 showed promising co-chemotherapeutic effects to the DOX against MCF-7ADR, indicating that this compound possesses potential as an auspicious lead chemical to target breast cancer cells resistant to doxorubicin.

Lung cancer remains a leading cause of mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for ~85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) exon 20 insertion mutant NSCLC is rare and associated with poor outcomes. Several novel generations (third-generation) of EGFR-tyrosine kinase inhibitors (TKIs) have been developed for the treatment of NSCLC and have shown antitumour potential. Therefore, the present study reviewed their efficacy and safety outcomes for this condition. A thorough literature searching was performed using the Cochrane Library, Web of Science, PubMed and Embase databases. Clinical trials published in English and reporting overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment relevant adverse events (TRAEs) of grade ≥3 were included for further analysis. A total of 13 studies were included. All included studies reported ORRs with a pooled ORR of 0.486 [95% confidence interval (CI), 0.369-0.602]. Subgroup analysis revealed the following ORRs: 0.731 (95% CI, 0.560-0.901; I2=0%) for YK-029A; 0.608 (95% CI, 0.511-0.705; I2=0%) for sunvozertinib; 0.602 (95% CI, 0.440-0.764; I2=80.2%) for furmonertinib; 0.602 (95% CI, 0.486-0.718; I2=84.5%) for befotertinib; 0.566 (95% CI, 0.236-0.896; I2=96.3%) for amivantamab; 0.444 (95% CI, 0.215-0.674; I2=0%) for BEBT-109; and 0.256 (95% CI, 0.178-0.334; I2=75.0%) for poziotinib. The pooled DCR, median PFS and median OS were 0.843 (95% CI, 0.740-0.946), 10.11 months (95% CI, 9.58-10.64 months; I2=78.8%; P<0.001) and 23.00 months (95% CI, 20.30-25.69 months; I2=44.8; P=0.178), respectively. The pooled incidence of TRAEs of grade ≥3 was 0.458 (95% CI, 0.336-0.580; I2=96.9%; P<0.001), with the incidence of the three most reported TRAEs (diarrhoea, thrombocytopenia and anaemia) demonstrated to be 0.112 (95% CI, 0.060-0.164), 0.065 (95% CI, -0.012-0.141) and 0.040 (95% CI, 0.005-0.076), respectively. In conclusion, the emerging EGFR-TKIs for NSCLC with EGFR exon 20 insertion have a promising treatment outcome with a manageable safety profile. However, further analysis is needed when more clinical data are released.

Treating hypoxic tumors is challenging due to their aggressive nature, resistance to standard treatments, often leading to poor outcomes. Hypoxic tumors create a unique environment that reduces the effectiveness of traditional treatments such as chemotherapy and radiotherapy. Human carbonic anhydrases (hCA IX and hCA XII) are involved in tumors survival and metabolism by regulating pH homeostasis, ferroptosis, metastatization, and other processes. Developing drugs that specifically target these enzymes has been demonstrated to disrupt the tumor survival mechanisms, leading to significant antitumor effects. This review discusses recent developments on antibody-drug conjugates (ADCs) and radioconjugates targeting hCA IX and hCA XII in hypoxic tumors. New approaches based on small molecule inhibitors and monoclonal antibodies such as girentuximab provided encouraging results in preclinical research and clinical trials. These advances highlight the potential of hCA-targeted therapies to improve cancer treatment for hypoxic tumors.

In situ activation of prodrugs or photosensitizers is a promising strategy for specifically killing tumor cells while avoiding toxic side effects. Herein, we originally develop a bioorthogonally activatable prodrug and pro-photosensitizer system to synchronously yield an aggregation-induced emission (AIE) photosensitizer and a chemotherapeutic drug for synergistic chemo-photodynamic-immunotherapy of tumors. By employing molecular engineering strategy, we rationally design a family of tetrazine-functionalized tetraphenylene-based photosensitizers, one of which (named TzPS5) exhibits a high turn-on ratio, a NIR emission, a typical AIE character, and an excellent ROS generation efficiency upon bioorthogonal-activation. With the aid of integrin- or mitochondria-pretargeting, TzPS5 is successfully applied for highly effective PDT ablation of cancer cells both in vitro and in vivo. On this basis, tumor-targeting TzPS5 (TzPS5-cRGD) is constructed and used jointly with a bioorthogonal prodrug, DOX-TCO, and the two are mutually activated to induce cooperative and tumor-specific PDT and chemotherapy, resulting in amplified therapeutic outcomes and improved biosafeties. Moreover, this combination modality elicits robust immunogenic cell death, stimulates systemic antitumor immunity, thereby suppressing both primary and distant tumors, and blocking the pulmonary tumor metastasis. This work is expected to provide a useful guidance for the rational design of activatable phototheranostic agents, and offer a new strategy for co-activation of prodrugs/pro-photosensitizers to boost synergistic antitumor chemo-photodynamic-immunotherapy.

A novel β-cyclodextrin-aza[5]helicene conjugate as theranostic platform for anticancer agents delivery in cancer cells is here reported. The carrier was synthesized via monotosylation of hydroxyethyl-β-cyclodextrin (HE-β-CD), followed by reaction with the synthesized aza[5]helicene, yielding the corresponding ammonium tosylate salt. The system was characterized by NMR, FTIR, UV-vis, and PL measurements, demonstrating favorable optical properties. The suitability of the fluorescent system to act as smart drug delivery system for cancer therapy was investigated by choosing gemcitabine (GMC) as a model drug. The GMC inclusion inside the system was evaluated by experimental and computational studies which confirmed the formation of a 1:1 complex between β-CD and GMC. The inclusion of GMC within the β-CD cavity led to a marked enhancement in its water solubility. Biological tests conducted on A549 cells revealed high cell internalization (∼80 %) and low cytotoxicity (IC50 = 262.7 µg mL-1) of the β-CD-aza[5]helicene conjugate. The results obtained by exploiting the host-guest chemistry of β-cyclodextrin combined with the unique photophysical properties of aza[5]helicene could pave the way for new anticancer therapies, by increasing the therapeutic index of anticancer agents endowed with poor solubility in water and characterized by systemic toxicity and, thanks to the fluorescent properties of the inserted probe, following their release into biological pathways.

Cancer is the second leading cause of death and chemotherapy is widely used and well-known for treating cancer, yet it has lots of adverse side effects, making the search for novel compounds imperative. We reported here design, synthesis, DFT analysis, anticancer evaluation and in-silico studies of new 1,3,4-oxadiazoles (4a-e).

IMC-038525 and IMC-094332 tubulin inhibitors' oxadiazole-linked aryl cores inspired the innovative compounds, and synthesis was accomplished in two steps followed by their characterization by spectral data. The HOMO and LUMO energy gap (ΔE) was determined to investigate compounds' (4a-e) stability followed by their anticancer activity at 10 μM and in-silico studies.

5-(4-Nitrophenyl)-N-(naphthalene-2-yl)-1,3,4-oxadiazol-2-amine (4b) demonstrated substantial anticancer activity against a few cell lines like SR, MDA-MB-435, MOLT-4, K-562, and HL-60(TB). 5-(3,4,5-Trimethoxyphenyl)-N-(naphthalene-2-yl)-1,3,4-oxadiazol-2-amine (4e) demonstrated promising anticancer activity against cell lines, UO-31, NCI-H226, CAKI-1, PC-3, and MCF7. The molecular docking against tubulin's colchicine binding site (PDB ID: 1AS0), displayed a docking score of -7.295 Kcal/mol and a H-bond interaction with Ala317 residue for the ligand 4e. The ligand 4e was found to interacted 24 amino acids of the tubulin protein in MD simulation investigation with moderate local conformational changes with ligand 4e (< 1 Å).

Drug resistance often involves preventing drug entry or expelling drugs from cells, severely affecting the therapeutic effect. We propose nanofunnel-shaped devices by pairing truncated graphene/boron nitride nanocones and nanotubes using curvature gradients and material properties to modulate energy barriers for unidirectional drug delivery. Molecular dynamics simulations demonstrate spontaneous delivery across models (ΔG = -14.14 to -27.87 kcal·mol-1 for C∨-C||, BN∨-BN||, C∨-BN||). The potential of mean force calculations reveal energy barriers scale as ΔG ∝ 1/R2, with BN nanotubes showing 20-30% higher barriers (e.g., -19.63 vs -14.14 kcal·mol-1 for graphene) due to stronger van der Waals interactions. In the BN∨-C|| model, increasing the tube radius (9.59 to 20.34 Å) or decreasing the cone angle (180-60°) can flip ΔG, enabling bidirectional control. This curvature-material synergy bypasses efflux mechanisms, offering a tunable platform to combat drug resistance and enhance therapeutic precision.

Inflammatory breast cancer (IBC) presents a formidable challenge due to its rapid progression and unique clinical characteristics within the various manifestations of breast cancer. Despite being rare, its aggressive nature demands innovative approaches beyond conventional treatments. Nanomedicine offers exciting possibilities for improving all types of breast cancer therapeutics including IBC. In this review, we critically assess the current treatment landscape for IBC, highlighting the limitations of traditional methods and addressing the pressing need for new therapeutic strategies. Although many nanomaterials have been explored for breast cancer therapeutics, either alone or in combination with other therapies, only a limited number of nanotherapeutics have been extensively studied for IBC treatment. This review further explores how advancements in nanotechnology, such as nanoparticle- mediated photothermal therapy, Photodynamic therapy, and nanomedicinal targeted therapies can offer novel avenues for addressing the unique biological, technological, and regulatory challenges posed by IBC. IBC-related various nanomedicines based combinatorial therapies are highlighted in this review. It also provides a forward-looking perspective on key research directions and clinical applications.

Magnetic mesoporous silica nanoparticles (MMS NPs) stand out as excellent options for targeted chemotherapy owing to their remarkable features, such as extensive surface area, substantial pore volume, adjustable and uniform pore size, facile scalability, and versatile surface chemistry. This review comprehensively explores the latest developments in MMS NPs, emphasizing their design, functionalization, and application in cancer therapy. Initially, we discuss the critical need for targeted and controlled drug delivery (DD) in oncology, highlighting the role of magnetic and MMs in addressing some challenges. Subsequently, the key features of MMS NPs, such as their high surface area, pore structure, and functionalization strategies, are examined for their impact on their DD performance for efficient cancer chemotherapy. The integration of chemotherapy methods such as photothermal therapy and photodynamic therapy with MMS NPs is also explored, showcasing multifunctional platforms that combine imaging and therapeutic capabilities. Finally, we identify the current challenges and provide future perspectives for the development and clinical translation of MMS NPs, underscoring their potential to reshape CT paradigms.

This study explores the synergistic therapeutic potential of Prussian Blue Erbium-Doped Hydroxyapatite (PB-Er-HAp) bioceramics in the context of photothermal therapy (PTT) and photodynamic therapy (PDT) for cancer treatment, highlighting their role in multimodal therapeutic approaches and imaging. PB-Er-HAp nanoparticles (NPs) were synthesized using a facile coprecipitation method to incorporate erbium (Er) into nanostructured hydroxyapatite (HAp) at various concentrations. Prussian Blue (PB) was functionalized onto the surfaces of these NPs, resulting in a final particle size of less than 50 nm. The therapeutic efficacy of the synthesized 1.0 mol % PB-Er-HAp NPs was evaluated in vitro, using MDA-MB-231 breast cancer cells. In vitro studies demonstrated that the PB-Er-HAp NPs exhibited significant PTT and PDT effects under 808 nm laser irradiation, effectively inducing cancer cell death through heat generation and reactive oxygen species production, respectively. In vitro experiments validated the ability of NPs to inhibit tumor growth in the MDA-MB-231 breast cancer cell line. This study emphasizes the potential of PB-Er-HAp NPs as a versatile platform for synergistic cancer therapy, combining PTT and PDT effects, while offering capabilities for biomedical imaging. Future research aims to further optimize these NPs and explore their clinical application, aiming toward enhanced therapeutic outcomes in cancer treatment.

Gaining significant attention in recent years, starvation therapy based on the blocking nutrients supply to cancer cells via blood occlusion and metabolic interventions is a promisingly novel approach in cancer treatment. However, there are many crucial obstacles to overcome to achieve effective treatment, for example, poor-targeting delivery, cellular hypoxia, adverse effects, and ineffective monotherapy. The starvation-based multitherapy based on multifunctional nanomaterials can narrow these gaps and pave a promising way for future clinical translation. This review focuses on the progression in nanomaterials-mediated muti-therapeutic modalities based on starvation therapy in recent years and therapeutic limitations that prevent their clinical applications. Moreover, unlike previous reviews that focused on a single aspect of the field, this comprehensive review presents a broader perspective on starvation therapy by summarising advancements across its various therapeutic strategies.

Targeted delivery can elevate the local drug concentration within tumor tissues, while minimizing drug distribution to normal tissues, thus enhancing the effectiveness of anti-tumor medications and reducing adverse effects and systemic toxicities. Nanobodies, the novel molecular pattern of antibodies characterized by their small size, high stability, strong specificity, and low immunogenicity, have been extensively applied in targeted drug delivery for tumor therapy. This review discusses structural disparities and functional advantages of nanobodies compared to other antibody fragments and full-length antibody. It also highlights nanobody applications in targeted tumor therapy, focusing on their use in modifying delivery systems, e.g., liposomes, EVs, micelles, albumin nanoparticles, gold nanoparticles, polymeric nanoparticles, and as nanobody-drug conjugates. This review delves into the methods applied for integrating nanobodies into different drug delivery carriers, in order to provide useful information for researchers developing nanobody-based targeted drug delivery systems.

The emerging clinical implications of medical foods and dietary supplements in cancer patients have been recognized. This study aimed to evaluate the perception and usage of these products in cancer patients undergoing chemotherapy.

Cross-sectional descriptive research was conducted by face-to-face interviews between October 2017 and February 2018. The participants provided written informed consent before data collection.

This study included 201 patients (mean age 55.9 years) with gastrointestinal, breast, gynecological, and respiratory tract cancers, primarily receiving antimetabolite or platinum-based regimens. Awareness of medical foods and dietary supplements was high, at 97% and 98%, respectively. Most patients (91.5% for medical foods, 80.1% for dietary supplements) believed these products could be used safely without side effects, and over 70% thought they could be used concurrently with chemotherapy. More than half of the patients reported receiving supplement information from friends or relatives, while 65.2% stated that healthcare providers did not ask about their uses. Notably, 69.7% and 51.2% of patients reported current use of medical foods and dietary supplements, respectively, but 61.7% did not disclose this to their healthcare providers primarily since they were not asked.

These findings highlight the need for healthcare professionals to actively address the use of medical foods and dietary supplements with cancer patients. Enhanced communication and guidance could ensure safe and effective integration of these products into supportive cancer care.

Solid tumors present significant therapeutic challenges due to their complex pathophysiology, including poor vascularization, dense extracellular matrix, multidrug resistance, and immune evasion. Conventional treatment strategies, such as chemotherapy, radiotherapy, and surgical interventions, are often associated with systemic toxicity, suboptimal drug accumulation at the tumor site, and chemoresistance. Nanostructured lipid carriers (NLCs) have emerged as a promising approach to enhance anticancer therapy. NLCs offer several advantages, including high drug loading capacity, improved bioavailability, controlled release, and enhanced stability. Recent advancements in active targeting strategies have led to the development of ligand-decorated NLCs, which exhibit selective tumor targeting, improved cellular uptake, and reduced systemic toxicity. By functionalizing NLCs with different targeting ligands, site-specific drug delivery can be achieved for better therapeutic efficacy. This review comprehensively explores the potential of ligand-decorated NLCs in solid tumor therapy, highlights their design principles, and mechanisms of tumor targeting. Furthermore, it discusses various receptor-targeted NLCs for the effective treatment of solid tumors. The potential of ligand-decorated NLCs in combination therapy, gene therapy, photothermal therapy, and photodynamic therapy is also explored. Overall, ligand-decorated NLCs represent a versatile and effective strategy to achieve better therapeutic outcomes in solid tumor therapy.

Recent cancer treatment development has focused on smart drugs, primarily using nanomaterials as carriers. However, concerns about nanomaterial fate and body clearance have led to exploring alternative approaches. This study presents a novel targeted smart drug that uses normal lymphocytic cells as carriers and exploits cancer microenvironment characteristics for drug release, avoiding systemic damage. The research investigated a complex combining gracillin (natural carrier) and the chemotherapeutic agent 5-bromouracil (5-BrU). Molecular docking showed the 5BrU-G complex had superior binding affinity (- 7.96 kcal mol-1) to glycosylated adhesion domain of human T lymphocyte glycoprotein CD2 (1CDB) cell surface receptors in silico. The complex was successfully synthesized through double replacement, precipitation, and neutralization reactions, confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cytotoxic and genotoxic studies revealed the selectivity of 5BrU-G against cancer cells (MDA-MB-231 and Caco-2) while saving normal cells (MCF-10A and CCD 841 CoN). Unlike 5-BrU alone, which showed significant genotoxicity in normal cells, the 5BrU-G complex demonstrated minimal toxic effects. The selective targeting mechanism of 5BrU-G relies on APOBEC3 enzyme activity, which is elevated in cancer cells but is absent in normal cells. This was confirmed when APOBEC3 inhibition prevented the complex's cancer-killing activity. This novel approach offers promising alternatives for improving cancer therapy efficacy while reducing side effects.

A salient challenge in cancer chemotherapy is the successful delivery of drugs to cancer cells. Therapeutic agents can be delivered to cancer cells in a targeted and efficient manner using nanoparticles (NPs). Herein, we present the molecular characterization of a novel binuclear Co(II) complex with octahedral geometry based on Schiff base from dehydroacetic acid and piperazine derivatives. DNA and BSA binding interactions were investigated using UV-Vis spectroscopy and gel electrophoresis. In vitro cytotoxicity of Co(II) complex was assessed against microbes and human cells (Cancer: MDA-MB-231, MCF7, A375, HepG2; Non-cancerous: HSF, WI-38) using well diffusion and MTT assays. Chitosan decorated with folic acid (CS-FA) was fabricated to encapsulate Co(II) complex, which may serve as a nano-targeted drug delivery system, to dampen its adverse effects on non-cancerous cells. TEM and DLS analysis confirmed nano-sized and stable monodisperse nanosuspension of both (CS-FA) and (CS-FA-Co(II) complex) systems. CS-FA-Co(II) complex NPs exhibited an 8.3-fold increase in cytotoxicity against folate-receptor-positive MDA-MB-231 cells, while remaining safe for folate-receptor-negative HSF cells. They also induced cell cycle arrest, inhibited migration, and triggered apoptosis by modulating Bax, Bcl-2, caspase-3, and CDH1. These findings highlight CS-FA NPs as a promising targeted delivery system for Co(II) complex-based cancer therapeutic agents, offering improved efficacy.

Nanoparticle albumin-bound (NAB) formulations are emerging as a viable strategy for the intravenous delivery of poorly water-soluble drugs. This study aims to improve the therapeutic profile of Bortezomib (BTZ), addressing its low solubility and significant systemic toxicity through the development of NAB-BTZ nanoparticles. The synthesized nanoparticles exhibited an average size of 296.47 ± 10 nm and a high drug encapsulation efficiency of 75%, and a drug loading of 10%. NAB-BTZ displayed a controlled, pH-sensitive release profile, with 59% release at pH 5.4 (mimicking tumor environments) and 46% at pH 7.4 after 12 h. In vitro assays demonstrated that NAB-BTZ significantly reduced the viability of 4T1 mammary carcinoma cells in a dose- and time-dependent manner, increasing late apoptosis from 6% to 54% after 48 h, compared to 24% for free BTZ. At molecular level, NAB-BTZ induced apoptosis by upregulating p53 and Bax, downregulating Bcl-2, and activating caspases 3 and 7. In vivo tests in a murine 4T1 breast cancer model showed that NAB-BTZ substantially inhibited tumor growth, achieving an average tumor volume of 916 mm3 by day 31 versus 1400 mm3 for free BTZ, leading to an improved survival rate of 100% compared to 83% in the BTZ group. Technetium-99m (99mTc) labeling and SPECT imaging confirmed enhanced targeting capability, showing preferential accumulation of NAB-BTZ in tumor sites compared to free BTZ. These findings suggest that NAB-BTZ not only improves antitumor efficacy but also enhances its safety profile, underscoring its clinical potential in breast cancer therapy.

Recent advances have revealed the overexpression of Neuropeptide Y (NPY) receptors in multiple cancers, positioning them as attractive molecular targets for cancer diagnostics and therapeutics. Despite this, a comprehensive roadmap for the rational development of anticancer agents targeting NPY receptors remains lacking. Therefore, we present the characteristics of NPY receptor subtypes, their abundance, and the correlation of their expression in different cancer types. It was found that NPY receptor subtypes 1 and 2 were extensively studied, especially in connection with breast and prostate cancer. Many tumors express NPYR, but only breast cancer tissue shows a significant difference in NPYR subtype expression levels between tumor and normal tissues, and, therefore, can represent a promising target. In the context of anticancer therapy, this review provides key findings from the use of wild-type and synthetic NPY analogs. We highlight the critical residues in the NPY sequence that play a critical role in interactions with receptors and provide the recent literature findings on NPY analogues as efficient and specific cancer-targeting agents. Potential solutions to improve NPY analogs' stability are provided, such as sequence modifications of linear peptides, peptide stapling, and conjugation for drug delivery systems. In general, NPY treatment can not be used efficiently as a single therapy but as a combinatorial therapy with anticancer drugs to improve the specificity of the treatment via high-affinity binding to the cancer cells and sensitizing them to chemotherapy.

DNA methylation is mediated by DNA methyltransferases (DNMTs), and the stability of their activity is essential for cellular fate. DNMT1 is considered one of the most promising targets for research. However, current detection techniques are limited in accurately quantifying its activity in peripheral blood. Here, a reaction system is developed known as DNMT1 Identification by Variable Activity (DIVA) for the highly sensitive detection of DNMT1 activity in the peripheral blood of breast cancer patients. DIVA can detect DNMT1 at levels as low as 10-7 U mL-1, with minimal time and cost. This method is applied to analyze 271 clinical samples, successfully evaluating tumor burden in patients staged I-IV. Finally, this method is utilized to assess the prognosis of 22 patients undergoing neoadjuvant therapy, demonstrating good consistency with ultrasound imaging results. It is believed that DIVA could serve as an effective auxiliary technique for both the early detection of breast cancer and evaluation of neoadjuvant therapy.

Two novel targeted drug delivery systems (DDSs) were designed: folate (FOL) conjugated (9, 9) carbon nanotube (CNT) loaded with 20 doxorubicin (DOX) molecules (FOL-CNT/20DOX) and folate (FOL) conjugated carboxylated (9, 9) CNT (COOH-CNT) loaded with 24 doxorubicin (DOX) molecules (FOL-COOH-CNT/24DOX). The targeted property to folate receptor α (FRα) was calculated using molecular dynamics (MD) calculations. The structures of the FRα/FOL-CNT/20DOX and FRα/FOL-COOH-CNT/24DOX complexes were analyzed in detail. Radial distribution functions were calculated to analyze the distribution of DOX molecules around the CNTs in the complexes. The variation of representative distances and angles between novel DDSs and FRα, number of hydrogen bonds, and secondary structures of FRα during the MD simulations were studied to analyze the dynamic properties of the novel DDSs targeted to FRα. We further analyzed the root mean square displacement and root mean square fluctuation in detail. The results indicate that the two novel DDSs were very stable and well targeted with FRα, and FOL-COOH-CNT/24DOX had better targeting and stability than FOL-CNT/20DOX. This study is expected to provide insights for the design of efficient nano drug delivery systems with good FRα targeting and controllable drug loading dosage.

Antrodia camphorata is a valued and scarce parasitic mushroom that exclusively proliferates on the inner cavity wall of the endangered tree Cinnamomum kanehirai Hay (Lauraceae), endemic to Taiwan. Historically, this fungus has been utilized in traditional medicine to treat liver cancer, diarrhea, abdominal pain, hypertension, and food and drug intoxication, among other ailments. Literature searches were performed in scientific databases. The results were compiled from peer-reviewed studies; the search was refreshed through January 2024 to incorporate the most recent research. In vitro studies have revealed that Antrodia camphorata possesses various pharmacological properties that prevent cancer, reduce inflammation, and improve liver function. This medicinal mushroom contains unique ergostane-type triterpenoids known as antcins, which exhibit numerous pharmacological properties. Seven naturally occurring methyl analogs of antcins have been identified so far. In this article, we reviewed and analyzed the properties of methyl antcinate A (MAA), a constituent of Antrodia camphorata and methyl derivative of antcin A. MAA has demonstrated important anti-apoptotic, anti-inflammatory, and gastro-protective properties, as well as significant anti-tumor, anti-cancer, and cytotoxic activities. The anti-cancer effect of MAA in various cancers is attributed to its ability to modulate signaling cascades in apoptotic pathways. A significant challenge is to initiate preclinical and clinical trials to assess its anti-tumor action in vivo, as this data is currently missing. Additionally, future research on the structure-activity relationship of antcins and their derivatives is expected to support their development as therapeutic agents for clinical use.

Chemotherapeutic treatments for breast cancer are often associated with severe toxicity due to the requirement of high concentrations of the drugs for efficacy. The combination of chemotherapy drugs along with repurposed drugs offers a promising strategy to enhance efficacy while reducing toxicity. However, the effectiveness of such combinations is likely to be hindered by improper metabolism of the drugs due to the sharing of the same metabolizing enzymes. In this study, we explored a novel approach to enhance the efficacy of Pimozide (repurposed drug) by combining it with chemotherapeutic drugs that utilize different metabolizing enzymes than Pimozide, thereby reducing metabolic load and toxicity. The Epirubicin-SAHA(Vorinostat)-Pimozide (ESP) combination emerged as highly synergistic, reducing the IC50 of Pimozide from 16.54 to 0.57 μM in MCF-7 cells and from 17.5 to 3.35 μM in MDA-MB-231 cells, representing a significant enhancement in efficacy. Mechanistic studies revealed increased intracellular reactive oxygen species (ROS) generation and activation of the intrinsic apoptosis pathway, as indicated by a 10-fold increase in the cleaved PARP levels. In MDA-MB-231 cells, there was also a 2-fold increase in p53 and a 10-fold increase in p21 expression, with a concomitant reduction in AKT signaling. Furthermore, the ESP combination reduced cancer stemness, invasiveness, fatty acid uptake, and lipid droplet accumulation, pointing to its broad impact on cancer cell survival and metabolism. These findings suggest that the ESP combination holds promise as an effective therapeutic strategy for breast cancer, with reduced toxicity and enhanced efficacy.

Methane (CH4) is identified to be an emerging anti-inflammation and anti-cancer molecule with high bio-safety, but the targeted delivery of CH4 is a thorny challenge. Herein, we propose a CH4 delivery strategy based on an intratumoral H2O2-triggered cascade reaction of ascorbic acid (AA)/methionine (Met), and have constructed a new nanomedicine (AMN) for tumor-targeted CH4 therapy. Encouragingly, AMN realizes the effective tumor-targeted delivery and intratumoral H2O2-responsive release of CH4, and exhibits significant anti-cancer effects and high bio-safety. Mechanistically, we have discovered that intratumoral released CH4 can not only induce the apoptosis of 4T1 tumor cells by inhibiting their mitochondrial metabolism, but also activate tumor immunotherapy by reprogramming tumor-associated macrophages (TAMs) phenotype (M2 to M1). The combination of the above anti-cancer pathways by virtue of tumor-targeted CH4 delivery makes contribution to outstanding anti-cancer efficacy of AMN. The proposed CH4 delivery strategy opens a new window for safe and effective tumor therapy.

Deoxyribonucleic acid (DNA) nanotechnology has rapidly emerged as a transformative field in biomedical research, offering innovative solutions for the detection and treatment of cancer. This review provides a comprehensive analysis of the role of DNA-based nanosystems in oncology, emphasizing their potential to address the limitations of conventional diagnostic and therapeutic approaches. Key advancements in DNA nanotechnology include the development of highly specific and sensitive nanostructures for early cancer detection, as well as precision-targeted delivery systems that enhance the efficacy of cancer therapies while minimizing side effects. The objectives of this review are threefold: first, to summarize the latest advancements in DNA nanotechnology, highlighting innovations in cancer biomarker detection and therapeutic applications; second, to explore the molecular mechanisms that enable these DNA-based nanosystems to interact with cancer cells with remarkable precision, including their design principles, self-assembly processes, and biological interactions; and third, to discuss the future implications of these technologies, considering the challenges, potential breakthroughs, and the steps needed to integrate DNA nanotechnology into clinical practice. By achieving these objectives, the review aims to offer insights into how DNA nanotechnology could revolutionize cancer care, providing new strategies for more personalized and effective treatments, and ultimately improving patient outcomes in the battle against cancer.

Lung cancer remains the leading cause of cancer-related deaths, and there is an urgent need for innovative therapies. MicroRNA (miRNA)-based gene therapy has shown promise, but efficient delivery systems are required for its success. This study investigates the use of extracellular vehicles (EVs) secreted by natural killer (NK) cells as delivery systems for miRNAs targeting PD-L1/PD-1 immune checkpoint and FOXM1, in combination with Carboplatin, to enhance anticancer efficacy in lung cancer models. NK-EVs were isolated from NK92-MI cells and characterized using nanoparticle tracking analysis (NTA), proteomics and Western blotting, confirming their exosomal characteristics. Gene ontology profiling and RNA-seq identified highly expressed miRNAs such as miR-5193 and miR-149-5p, which were loaded into NK-EVs via electroporation. Agarose gel electrophoresis confirmed their entrapment and Quickdrop spectrophotometer was used to estimate the quantity. In vitro, miRNA-loaded NK-EVs demonstrated significant cytotoxicity against Osimertinib-resistant PDX (TM0019, Jackson Labs) and H1975R (with L858R mutations) lung cancer cells, with approximately 1.2 to 1.6-fold (p < 0.01) decrease in cell viability compared to NK-EVs alone. In vivo, the combination of miRNA-loaded NK-EVs and Carboplatin significantly reduced tumor volumes (3.5 to 4-fold, p < 0.001) in PDX and H1975R xenograft models, with the most pronounced effect observed in combination therapies. Western blot analysis showed downregulation of tumor-associated markers: PD-1/PD-L1, FOXM1, Survivin, NF-κB and others vs untreated group, p < 0.001) suggesting immune checkpoint inhibition, apoptosis and anti-inflammatory activity. These findings highlight the potential of NK-EVs as effective carriers for miRNAs in combination with chemotherapy, offering a promising therapeutic strategy for NSCLC with EGFR mutations.

Glioma, particularly glioblastoma (GBM), remains a highly aggressive and challenging tumour, characterised by poor prognosis and limited therapeutic options. LSM2, an RNA-binding protein, has been implicated in tumour progression, yet its role in glioma remains underexplored. This study aims to investigate the expression, prognostic significance, and molecular mechanisms of LSM2 in glioma, focusing on its impact on RNA splicing regulation.

Clinical and transcriptomic data from 163 GBM and 518 lower-grade glioma (LGG) cases from The Cancer Genome Atlas (TCGA) were analysed to assess LSM2 expression and its prognostic value. RNA sequencing was performed on LSM2 knockdown in T98G glioblastoma cells to identify differentially expressed genes (DEGs) and alternative splicing events (ASEs). Bioinformatics tools were employed to perform functional enrichment analyses and construct protein-protein interaction (PPI) networks.

LSM2 expression was significantly elevated in gliomas, particularly in GBM and in tumours with 1p/19q non-deletion or IDH1 mutation (p < 0.001). High LSM2 expression was correlated with shorter overall survival (HR = 1.7, p = 0.01). Knockdown of LSM2 in T98G cells identified 728 upregulated and 1,720 downregulated genes, alongside 1,949 splicing alterations, which primarily affected pathways related to RNA metabolism, DNA damage response, and cell cycle regulation. Key hub genes such as TLN1, FN1, and IRF7 were associated with glioma progression and poor prognosis.

Our findings demonstrate that LSM2 plays a critical role in glioma progression through the regulation of RNA splicing dynamics. Elevated LSM2 expression serves as a prognostic biomarker and offers promising potential as a therapeutic target in glioma.

Cancer remains a significant global health challenge, necessitating the development of more effective therapeutic strategies. This work presents a novel glutathione (GSH)-responsive platform designed to enhance the delivery and efficacy of the anticancer drug mertansine (DM1) through the modulation of pendant groups in polycarbonate-drug conjugates. By systematically varying the hydrophobicity of the pendant groups, we investigated their effects on nanostructures, GSH sensitivity, colloidal stability, drug release profiles, and the in vitro anticancer efficacy of these polymeric nanoparticles, revealing that more hydrophobic pendant groups effectively reduce GSH accessibility for the nanoparticle cores, improve colloidal stability, and slow drug release rates. The results underscore the critical importance of polymer structures in optimizing drug delivery systems and offer valuable insights for future research on advanced nanomaterials with enhanced drug delivery for cancer therapies.

This study aims to assess the potential anticancer activity of lemongrass essential oil (LEO) using in vitro and in silico methods. The steam hydrodistillation of the aerial parts yielded 3.2% (wt) LEO. The GC-MS analysis of the LEO revealed the presence of α-citral (37.44%), β-citral (36.06%), linalool acetate (9.82%), and d-limonene (7.05%) as major components, accompanied by several other minor compounds. The antioxidant activity, assessed using the DPPH assay, revealed that LEO exhibits an IC50 value of 92.30 μg/mL. The cytotoxic effect of LEO, as well as LEO solubilized with Tween-20 (LEO-Tw) and PEG-400 (LEO-PEG), against a series of cancer cell lines (A375, RPMI-7951, MCF-7, and HT-29) was assessed using the Alamar Blue assay; the results revealed a high cytotoxic effect against all cell lines used in this study. Moreover, neither one of the tested concentrations of LEO, LEO-PG, or LEO-TW significantly affected the viability of healthy HaCaT cells, thus showing promising selectivity characteristics. Furthermore, LEO, LEO-PG, and LEO-TW increased ROS production and decreased the mitochondrial membrane potential (MMP) in all cancer cell lines. Moreover, LEO treatment decreased all mitochondrial respiratory rates, thus suggesting its ability to induce impairment of mitochondrial function. Molecular docking studies revealed that LEO anticancer activity, among other mechanisms, could be attributed to PDK1 and PI3Kα, where the major contributors are among the minor components of the essential oil. The highest active theoretical inhibitor against both proteins was β-caryophyllene oxide.

Acute lymphoblastic leukemia (ALL) is a significant concern in both pediatric and adult demographics. Despite 156 approved cancer therapies based on small molecules, a mere five apply to all types of leukemia. Unfortunately, adherence to these treatments is low due to adverse side effects. Consequently, there is an urgent need to identify more effective treatment options for ALL. This study presents a potential solution. We have designed over fifty analogs of carbamazepine, utilizing a combination of ligand-based and structure-based drug design methodologies. Among these analogs, we identified the CR80 analog, which demonstrated predicted binding values of -8.66 kcal/mol against beta-tubulin, a favorable LogP, and IC50 values suitable for in vitro evaluation. The CR80 compound was synthesized with a yield of 50% and subsequently assessed in vitro against the U-937 cell line. It obtained an IC50 value of 0.8 micromolar to 1 micromolar and a selectivity index of two, thus marking it as a promising candidate for in vivo studies.

The multicenter, prospective MiroCIP observational study investigated the incidence, risk factors, and outcomes of chemotherapy-induced peripheral neuropathy (CIPN) by oxaliplatin- and taxane-based chemotherapies but did not examine their differences in detail. This post hoc subanalysis explored the differences between oxaliplatin- and taxane-based chemotherapy, in terms of CIPN symptom profile, severity, and response to analgesics.

Patients with colorectal, gastric, non-small cell lung, or breast cancer, scheduled to receive oxaliplatin- or taxane-based chemotherapy, were followed for 12 months to assess the severity of sensory CIPN, by the Common Terminology Criteria for Adverse Events, and associated subjective and objective symptoms.

Overall, 91 patients received oxaliplatin and 131 received a taxane. At 12 months, CIPN prevalence was 74.6% with oxaliplatin and 55.2% with a taxane. Grade ≥ 2 CIPN peaked at 9 months with oxaliplatin and at 3 months with a taxane, with most symptom scores following a similar trajectory. Analgesic efficacy differed between subgroups, providing marked reductions in pain/tingling scores in the taxane group but minimal effect in the oxaliplatin group.

CIPN course and symptoms vary with oxaliplatin- or taxane-based chemotherapy. Effective management should be tailored to the type of chemotherapy: oxaliplatin-treated patients may benefit from continuous monitoring of CIPN symptoms, whereas it may be beneficial for taxane-treated patients to receive appropriate analgesics at CIPN onset.

Japan Registry of Clinical Trials jRCTs031210101.

Solid cancer contains a complicated communication network between cancer cells and components in the tumor microenvironment (TME), significantly influencing the progression of cancer. Exosomes function as key carriers of signaling molecules in these communications, including the intricate signalings of tumor-associated macrophages (TAMs) on cancer cells and the TME. With their natural lipid bilayer structures and biological activity that relates to their original cell, exosomes have emerged as efficient carriers in studies on cancer therapy. Intrigued by the heterogeneity and plasticity of both macrophages and exosomes, we regard macrophage-derived exosomes in cancer as a double-edged sword. For instance, TAM-derived exosomes, educated by the TME, can promote resistance to cancer therapies, while macrophage-derived exosomes generated in vitro have shown favorable potential in cancer therapy. Here, we depict the reasons for the heterogeneity of TAM-derived exosomes, as well as the manifold roles of TAM-derived exosomes in cancer progression, metastasis, and resistance to cancer therapy. In particular, we emphasize the recent advancements of modified macrophage-derived exosomes in diverse cancer therapies, arguing that these modified exosomes are endowed with unique advantages by their macrophage origin. We outline the challenges in translating these scientific discoveries into clinical cancer therapy, aiming to provide patients with safe and effective treatments.