Cancer Therapy Research Articles

Metal-organic frameworks as nanoplatforms for combination therapy in cancer treatment.

The integration of nanotechnology into cancer treatment has revolutionized chemotherapy, boosted its effectiveness while reduced side effects. Among the various nanotherapeutic approaches, metal-organic frameworks (MOFs) stand out as promising carriers for targeted chemotherapy, with the added benefit of enabling combination therapies. MOFs, composed of metal ions or clusters linked by coordination bonds, tackle critical issues in traditional cancer treatments, such as poor stability, limited efficacy, and severe side effects. Their key advantages include customizable size and shape, diverse compositions, controlled porosity, large surface areas, ease of modification, and biocompatibility. This review highlights recent advancements in the use of MOFs for cancer therapy, showcasing their role in both monotherapies and combination strategies. Additionally, it explores the future potential and challenges of MOF-based platforms in tumor treatment.

Editorial for Special Issue “Cellular Senescence: Recent Cellular Advances and Discoveries”

Cellular senescence has emerged as a fascinating frontier in biological research and now presents profound implications across diverse fields, from aging research to cancer therapy [...]

Abstract IA017: Transferrin receptor targeting chimeras (TransTACs) for targeted degradation of membrane and extracellular proteins in cancer

Abstract The membrane and extracellular proteome plays central roles in health and disease. Harnessing TfR1, a constitutive, rapidly internalizing receptor overexpressed in a broad spectrum of cancers, we developed Transferrin Receptor Targeting Chimeras (TransTACs) for targeted degradation of membrane and extracellular proteins. In two applications, we show that TransTACs enabled the targeting of drug-resistant epidermal growth factor receptor (EGFR)-driven lung cancer and the reversible control of primary Chimeric Antigen Receptor (CAR)-T cells. TransTACs represent a promising new family of bifunctional antibodies for precise manipulation of membrane proteins and for targeted cancer therapy. Citation Format: Xin Zhou. Transferrin receptor targeting chimeras (TransTACs) for targeted degradation of membrane and extracellular proteins in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA017.

Cellular and molecular aspects of drug resistance in cancers.

Cancer drug resistance is a multifaceted phenomenon. The present review article aims to comprehensively analyze the cellular and molecular aspects of drug resistance in cancer and the strategies employed to overcome it. A systematic search of relevant literature was conducted using electronic databases such as PubMed, Scopus, and Web of Science using appropriate key words. Original research articles and secondary literature were taken into consideration in reviewing the development in the field. Cancer drug resistance is a pervasive challenge that causes many treatments to fail therapeutically. Despite notable advances in cancer treatment, resistance to traditional chemotherapeutic agents and novel targeted medications remains a formidable hurdle in cancer therapy leading to cancer relapse and mortality. Indeed, a majority of patients with metastatic cancer experience are compromised on treatment efficacy because of drug resistance. The multifaceted nature of drug resistance encompasses various factors, such as tumor heterogeneity, growth kinetics, immune system, microenvironment, physical barriers, and the emergence of undruggable cancer drivers. Additionally, alterations in drug influx/efflux transporters, DNA repair mechanisms, and apoptotic pathways further contribute to resistance, which may manifest as either innate or acquired traits, occurring prior to or following therapeutic intervention. Several strategies such as combination therapy, targeted therapy, development of P-gp inhibitors, PROTACs and epigenetic modulators are developed to overcome cancer drug resistance. The management of drug resistance is compounded by the patient and tumor heterogeneity coupled with cancer's ability to evade treatment. Gaining further insight into the mechanisms underlying medication resistance is imperative for the development of effective therapeutic interventions and improved patient outcomes.

Near Infrared Thermoluminescent Liposome Sensor for Real‐Time Monitoring of Photothermal Therapy and Magnetic Hyperthermia

AbstractLiposomes are established in the clinic as drug delivery system, and can be designed for heat‐triggered drug release. Thermal nanotherapies, like magnetic nanoparticle hyperthermia (MNH) and photothermal therapy (PTT), show great promise for cancer therapy and other diseases, but the great challenge of them is temperature detection. In this study, a thermoluminescent vesicle for real‐time monitoring of PTT and MNH is developed. The temperature sensor is a liposome containing IR780 dyes incorporated in the membrane. For PTT, the liposome is the thermal agent and temperature sensor, while for MNH only the sensor, since the nanoheaters are Mn‐based iron oxide nanoparticles. Mn‐ferrite nanoparticles showed a good response at low field MNH conditions. The photothermal conversion efficiency of the liposomes altered from 11% to 22%. Thermal sensitivity varied from 0.3% to 5.0% and change after freeze‐drying, while repeatability ranged from 0.91 to 0.98. Photostability studies of MNH and PTT with five heat‐cooling cycles confirmed the temperature sensor application. In vivo and post‐mortem studies using the B16F10 murine tumor model are reported. After intratumoral injection of the thermoluminescent vesicle a blue‐like fluorescence peak shift of ≈20 nm is observed, which maintains the thermometry capabilities and reveals remotely the intratumoral temperature during PTT. The results demonstrate that the near‐infrared thermoluminescent liposome is able to real‐time monitoring the thermal therapy.

Therapeutic targeting of cGAS-STING pathway in lung cancer.

The presence of DNA in the cytosol triggers a protective response from the innate immune system. Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) is an essential cytosolic DNA sensor that triggers a potent innate immune response. As a result of this signaling cascade reaction, type I interferon and other immune mediators activate an immune response. The cGAS-STING pathway has great anticancer immunity-boosting potential since it produces type I interferons. The detection of double-stranded DNA (dsDNA) in response to various stimuli initiates a protective host's cGAS-STING signals. So, it is clear that a substantial relationship is expected between cancer biotherapy and the functioning of the cGAS-STING pathway. Several STING agonists with promising outcomes have been created for preclinical cancer therapy research. Notably, immunotherapy has dramatically extended patient survival and radically altered the course of lung cancer treatment, particularly in more advanced instances. However, this method is still ineffective for a large number of lung cancer patients. cGAS-STING can overcome resistance and boost anticancer immunity by stimulating the activity of many pro-inflammatory mediators, augmenting dendritic cell cross-presentation, and initiating a tumor-specific CD8+ T cell response. This review aims to present the most recent results on the functionality of the cGAS-STING pathway in cancer progression and its potential as an immunotherapy target, with a focus on lung cancer.

Engineered Nanostructures for Sonothermal Therapy

AbstractSonothermal therapy (STT) has become increasingly attractive recently as a noninvasive, safe, and nonionizing methodology. STT, as a newly emerging heat‐enabled therapeutic approach, can rely on built‐in bubble cavitation and thermal energy‐electron recombination of sonothermal agents (STAs) activated by ultrasound (US) irradiation. In this domain, STT‐enabled nanomedicine is considered a potential treatment for abnormal cell killing and normal cell renewing, which addresses the drawbacks of nonspecific heating in conventional microbubbles, side effects, and poor tissue penetration of available thermal‐based therapies. Herein, a comprehensive review on the efficiency of STT in tumor ablation, infection therapy, and tissue regeneration is presented. Moreover, this review focuses on the benefits of STT as a therapeutic hot topic that can be used for nonantibiotic treatments, noninvasive heat‐activated tissue regeneration, and highly efficient local cancer therapy. In addition, rational design of STAs, mechanistic innovations, and prospects of STT will also be provided.

Differential cytotoxicity of methanol and water extracts from Bacopa monnieri (L.) Wettst and Ceratophyllum demersum L. on HepG2 and THLE2 cells

This study evaluated the cytotoxic effects of methanol and water extracts from Bacopa monnieri (L.) Wettst and Ceratophyllum demersum L. on HepG2 (liver cancer) and THLE2 (normal liver) cell lines using XTT assay. The extracts were tested at concentration range of 12.5-400 µg/mL. In HepG2 cells, the water extract of B. monnieri at 400 µg/mL exhibited the highest cytotoxicity, reducing cell viability to 11.08%, which was statistically significant (p < 0.05) compared to other treatments. The methanol extract of C. demersum at 12.5 µg/mL had the least effect, maintaining 94.84% cell viability. For THLE2 cells, the water extract of B. monnieri (400 µg/mL) also showed the greatest reduction in cell viability (30.85%). The water extract of C. demersum at the same concentration resulted in similar viability (32.01%), with no significant statistical difference (p > 0.05). The lowest concentrations of methanol and water extracts of C. demersum showed minimal effects (97.55% and 97.74% viability, respectively). Median inhibitor concentration (IC50) analysis revealed that B. monnieri’s water extract was most effective, with IC50 values of 68.45 µg/mL for HepG2 and 127.05 µg/mL for THLE2 cells. In contrast, C. demersum’s methanol extract had the highest IC50 values (173.35 µg/mL and 228.46 µg/mL, respectively), indicating lower cytotoxicity. Heatmap and cluster analyses highlighted the selective cytotoxicity of C. demersum on cancer cells with minimal effects on normal cells, showing its potential for targeted cancer therapy.

Quantitative assessment of 167Tm isotope production: experimental data analysis and model validation.

167Tm is an effective radioisotope for use in theragnostic purposes. This study aims to find the best alternative routes for producing 167Tm for appropriate cancer therapy and diagnostics. In this study, we comprehensively analyzed production cross-sections of 167Tm and investigated the behavior of these reactions using six different level density models and refined optical model potential (OMP) parameters with the nuclear reaction code TALYS 1.96. Using this code, we estimated the specific activity and production yield for promising production routes. For characterizing the 167Tm isotopes, the energy distribution of 167Tm was also analyzed for each prominent reaction by particle and heavy ion transport code system (PHITS). The maximum specific activity was estimated as 52.6-75.2GBq/g with a production yield of 20.2-32.7GBq/mAh for the route 169Tm(p,x)167Tm. The experimental value was reproduced with good agreement by TALYS adjusting different OMP parameters. 169Tm(p,x)167Tm is the alternative route for producing 167Tm, for which TALYS can reproduce the result more accurately.

Potential Antimicrobial and Cytotoxic Activity of Caralluma indica Seed Extract

Background: Plant-derived phytochemicals are crucial in fighting bacterial infections and in cancer therapy. Objective: This study investigates the phytochemical composition of the ethanolic extract obtained from Caralluma indica (C. indica) seeds and assesses its antimicrobial, anticancer, and antioxidant activities. Results: GC-MS analysis found 30 phytochemicals in C. indica seeds, including 5 bioactive compounds that have been shown to have antioxidant, antimicrobial, and cytotoxicity properties, through in silico evaluation. Phytochemical screening of C. indica identified and measured the phenolic compounds, providing insight into its bioactive potential and therapeutic properties. C. indica exhibited robust antioxidant capacity (DPPH, ABTS, nitric oxide, and H2O2 radical scavenging) alongside potent antimicrobial activity against oral pathogen and cytotoxicity activity on a human oral squamous carcinoma cell line (OECM-1) (EC50 of 169.35 µg/mL) and yeast cell Saccharomyces cerevisiae (215.82 µg/mL), with a selective index of 1.27. The subminimum % MBC/MFC of C. indica significantly reduced biofilm formation against oral pathogens (p < 0.05). Molecular docking studies showed a strong correlation (r = 0.862) between antifungal and anticancer targets, suggesting that the antimicrobial agents in C. indica contribute to cancer prevention mechanisms. Conclusions: These findings propose C. indica seeds as promising candidates for combating oral pathogens, inhibiting biofilm formation, and reducing the risk of oral cancer progression.

Parenteral Nutrition in the Health-Care Setting: A Comprehensive Review

Parenteral Nutrition (PN) is a critical therapeutic technique that delivers necessary nutrients straight into the circulation, bypassing the gastrointestinal system. This strategy is critical for people who are unable to acquire appropriate nourishment through oral or enteral routes owing to a variety of medical issues. PN first appeared in the mid-twentieth century, primarily to help those who were very malnourished or recuperating from significant surgery. As medical understanding of nutrition grew, so did the complexity and customization of PN formulations, allowing for personalized nutritional support depending on metabolic demands. The indications for PN are diverse, including gastrointestinal diseases, cancer therapies, severe illnesses, neurological issues, and pediatric demands. Patients suffering with Crohn's illness, short gut syndrome, and severe malnutrition caused by cancer therapies frequently rely on PN to maintain their nutritional status. Furthermore, critically sick patients in intensive care settings typically encounter elevated metabolic demands, needing efficient nutritional therapies that oral feeding cannot deliver. While PN has considerable advantages, such as increased recovery, malnutrition prevention, and quality of life, it is not without hazards. Infections, metabolic abnormalities, and liver dysfunction are all possible complications, emphasizing the importance of thorough monitoring and following best practices in PN administration. A multidisciplinary approach including healthcare specialists from several professions is required to achieve the best outcomes for patients seeking PN. Looking ahead, technological developments, personalized dietary techniques, and artificial intelligence integration promise to improve the safety and efficacy of PN. Continuous research and innovation are required to solve current difficulties and enhance the overall quality of care for patients requiring parenteral feeding. As the healthcare environment shifts, PN will remain an important component of nutritional support, requiring continuing attention and development in clinical practice.

The Role of Dopamine in Gastric Cancer—A Systematic Review of the Pathogenesis Phenomena Developments

Background: In the last few decades, it has been emphasized that dopamine, a well-known neurotransmitter with multiple roles in central nervous system, is also implicated in the activity of peripheral tissues and organs, more specifically influencing the gastrointestinal system (GI). Methods: We registered a protocol under the CRD42024547935 identifier in the Prospero register of systematic reviews. Furthermore, using the Population, Intervention, Comparison, Outcome, and Study Design strategy to guide our study rationale, and under the Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations, we conducted a qualitative systematic literature search based on the PubMed, Scopus, and Web of Science databases using the “gastric cancers AND dopamine” search criteria. We obtained 68 articles from PubMed, 142 articles from Scopus, and 99 articles from the Web of Science database. Results: Within gastric cancer biology, dopamine has notable effects on STAT-3 and DARPP-32. STAT-3, a transcription factor involved in cellular proliferation and invasion, plays a significant role in cancer progression. Conclusions: Understanding the roles of dopamine in cancer, beyond aspects such as cancer cell invasion, immune response modulation, or tumor growth, could guide the development of new cancer therapies by modulating its pathways, especially the DARPP-32/CXCR4/CXCL-12 complex axis, in order to improve the morbidity and mortality caused by this type of cancer.

Identification of potential methyltransferase NSD2 enzymatic inhibitors through a multi-step structure-based drug design.

Reversing aberrant protein methylation levels is widely recognized as a key focus in cancer therapy. As an essential lysine methylation regulator, NSD2 (Nuclear receptor-binding SET Domain 2, also known as WHSC1/MMSET) regulates chromatin structural sparsity and DNA repair processes. Abnormal enhancement of NSD2 methylation activity (caused by NSD2 overexpression and point mutations) has been closely related to the initiation and development of various cancers and diseases. However, the lack of selective inhibitors hinders further therapeutic intervention and limits the exploration of its biological mechanism. Therefore, this study developed an integrated approach that includes binding feature pharmacophore modeling, gradient database screening of 120 million compounds, flexible docking, and molecular dynamic simulation. This approach was used to identify hit compounds targeting the substrate/coenzyme binding site of NSD2. Subsequently, 20 lead compounds were retrieved by using molecular docking analysis and ADMET prediction. Finally, MD simulations were performed to validate the binding stability of selected drug candidates. The findings indicated that these newly obtained compounds might be potent NSD2 inhibitors. We hope the integrated virtual screening approach will provide a valuable idea for discovering novel H3K36 methyltransferase inhibitors.

Novel affibody molecules targeting the AXL extracellular structural domain for molecular imaging and targeted therapy of gastric cancer.

Gastric cancer (GC) has a poor prognosis and high mortality because it is often diagnosed at an advanced stage. Targeted therapeutics are considered an important class for advanced GC treatment. However, the fewer effective therapeutic targets and the poor coverage of the GC population limit the use of GC targeted therapies. Recent research suggests that the AXL receptor tyrosine kinase (AXL) plays an vital role in the survival and proliferation of GC cells, and blocking AXL pathway may be an effective strategy for targeted therapies. On the other hand, the affibody molecule, with its small size and faster penetration of tissue, has great potential in tumor imaging and targeted therapy. In this study, we report the novel AXL-binding affibody molecules (ZAXL:239) screened by a phage-displayed peptide library. The ZAXL:239 could specifically bind and interact with AXL proteins in vitro and in vivo, as demonstrated by surface plasmon resonance, co-immunoprecipitation, immuno-fluorescence co-localization, and nearinfrared fluorescent imaging. In addition, ZAXL:239 affibody molecules could significantly inhibit the proliferative activity and induce apoptosis of AXL-positive GC cells by decreasing the phosphorylation levels of the PI3K/AKT1 and MEK/ERK pathway, leading to the suppression of the downstream nuclear protein c-myc. Moreover, ZAXL:239 was found to have significant anti-tumor effects in AXL-positive GC transplantation tumor nude mouse models. In brief, we provide strong evidence that the novel ZAXL:239 affibody molecules have great potential as a potent tumor-specific molecular imaging and targeted therapeutic agents for GC.

Natural killer cells as promising candidates in Cancer therapeutics and related immune resistance in tumor microenvironment

Natural killer (NK) cells, as critical components of the innate immune system, have emerged as promising candidates in cancer therapy due to their ability to recognize and destroy tumor cells without prior sensitization. Their mechanisms of action, including perforin-granzyme release and antibody-dependent cellular cytotoxicity (ADCC), position them as versatile agents in cancer immunotherapy. Recent advancements, such as chimeric antigen receptor (CAR)-NK cells and cytokine-based stimulation, have demonstrated enhanced efficacy and reduced side effects compared to conventional immunotherapies. However, the immunosuppressive tumor microenvironment (TME) remains a significant obstacle, imposing challenges like immune checkpoint activation, cytokine suppression, and metabolic constraints that impair NK cell activity. This paper explores the therapeutic potential of NK cells, the challenges of immune resistance in the TME, and emerging strategies to enhance NK cell efficacy. Addressing these challenges is crucial for optimizing NK cell-based treatments and achieving durable responses in cancer patients.

Upconversion Nanoparticle-Anchored Metal-Organic Framework Nanostructures for Remote-Controlled Cancer Optogenetic Therapy.

Optogenetics, a revolutionary technique utilizing light-sensitive proteins to control cellular functions with high spatiotemporal precision, presents a promising avenue for disease treatment; however, its application in cancer therapy remains constrained by limited research. Herein, we introduce a pioneering strategy for remote-controlled optogenetic cancer therapy, synergistically merging optogenetics with ion therapy, which incorporates ion self-supply, in situ ion channel construction, and near-infrared (NIR) light-activated ion therapy, facilitating remote and noninvasive manipulation of cellular activities in deep tissues and living animals. We report the facile synthesis of water-dispersible upconversion nanoparticle (UCNP)-metal-organic framework (MOF) nanohybrids capable of effectively delivering plasmid DNA to cancer cells, thereby enabling the in situ expression of photoactivatable cation channels. The pH-responsive MOF components serve as a reservoir for metal cations, which are released in the acidic microenvironment of tumors, while the UCNP components function as remote-controlled transducers, converting near-infrared (NIR) light into visible light to activate the cation channels and allowing the cancer influx of released metal cations for ion therapy. The proposed remote-controlled cancer optogenetic therapy demonstrates its effectiveness across multiple tumor models, including subcutaneous colon tumors, subcutaneous breast tumors, and orthotopic breast tumors. This study represents a significant step toward the realization of optogenetics in clinics, with substantial potential for advancing cancer therapy.

Microbiota and Cytokine Modulation: Innovations in Enhancing Anticancer Immunity and Personalized Cancer Therapies

The gut microbiota plays a crucial role in modulating anticancer immunity, significantly impacting the effectiveness of various cancer therapies, including immunotherapy, chemotherapy, and radiotherapy. Its impact on the development of cancer is complex; certain bacteria, like Fusobacterium nucleatum and Bacteroides fragilis, can stimulate the growth of tumors by causing immunological evasion and inflammation, while advantageous strains, like Faecalibaculum rodentium, have the ability to suppress tumors by modifying immune responses. Cytokine activity and immune system regulation are intimately related. Cytokines including TGF-β, IL-6, and IL-10 promote tumor development by inhibiting efficient immune surveillance. The gut microbiome exhibits a delicate balance between pro- and anti-tumorigenic factors, as evidenced by the enhancement of anti-tumor immunity by cytokines such as IL-12 and IFN-γ. Improved immunotherapy responses are linked to a diverse microbiota, which is correlated with higher tumor infiltration and cytotoxic T-cell activation. Because microbial metabolites, especially short-chain fatty acids, affect cytokine expression and immune cell activation inside the tumor microenvironment, this link highlights the need to maintain microbial balance for optimal treatment effects. Additionally, through stimulating T-cell activation, bacteria like Lactobacillus rhamnosus and Bifidobacterium bifidum increase cytokine production and improve the efficacy of immune checkpoint inhibitors (ICIs). An option for overcoming ICI resistance is fecal microbiota transplantation (FMT), since research suggests that it improves melanoma outcomes by increasing CD8+ T-cell activation. This complex interaction provides an opportunity for novel cancer therapies by highlighting the possibility of microbiome modification as a therapeutic approach in personalized oncology approaches.

Photodynamic Therapy in Cancer: Principles, State of the Art, and Future Directions

Since its discovery more than 100 years ago, photodynamic therapy (PDT) has become a potent strategy for the treatment of many types of cancer [...]

Recent Advances in Marine-Derived Bioactives Towards Cancer Therapy

The increase in cancer incidence in recent years necessitates urgent exploration of novel and alternative sources of natural bioactives for targeted cancer therapy. Approximately 75% of the Earth’s surface is covered by oceans, which are thought to harbor untapped physiologically active compounds with potential efficacy against cancer. Recently, a growing focus has been on isolating and investigating novel bioactive compounds derived from marine sources. Bioactive metabolites with diverse chemical structures, isolated from various marine species such as algae, mollusks, and actinomycetes, demonstrate potential efficacy against a wide range of cancers. To our knowledge, this is one of the articles that has reviewed recent papers on the application of marine-derived bioactives in targeted cancer therapy. This study aims to showcase some of the most current developments in targeted cancer therapy with various bioactives that have been identified from marine sources.

Metformin: exploring its potential as an anticancer drug

Metformin is a commonly used hypoglycemic agent that has received much attention in recent years for its potential in cancer therapy. This paper reviews and concludes the anti-cancer mechanisms of metformin and its clinical applications in different cancer types. It was found that metformin indirectly inhibits cancer cell growth by activating AMPK and inhibiting the mTOR pathway and decreasing insulin and IGF-1 levels. In addition, metformin directly inhibits cancer cell proliferation by inducing apoptosis and autophagy. Clinical data suggest that metformin significantly improves survival and reduces cancer recurrence in patients with gastric, renal, endometrial and esophageal cancers. However, despite the preliminary evidence provided by existing studies, discrepancies remain between the results of different studies, and further large-scale randomized controlled trials are needed to validate its anticancer effects and optimize application strategies. Future studies should focus on clarifying the specific mechanism of action of metformin and its potential application prospect in individualized therapy.