Strategy For Cancer Treatment Research Articles

Molecular Genetic Factors of Risk Stratification of Lymph Node Metastasis in Endometrial Carcinoma.

According to epidemiological studies, endometrial carcinoma is one of the most frequently diagnosed malignancies of the female reproductive system, with an increasing incidence. Currently, the risk stratification of this neoplasm takes into account the stage, degree of tumor differentiation, histological type and depth of myometrial invasion. Since the publication of the last International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer in 2009, numerous reports have appeared on the molecular characteristics of different types of endometrial carcinoma. Taking this into account, the FIGO Committee determined in 2023 that changes and updates to the staging system are justified to reflect new information about this tumor. Due to the high prevalence of the disease and mortality from endometrial cancer, an in-depth study of the molecular genetic characteristics of tumor cells is relevant; the results of such studies can be used to improve the efficiency of diagnosis, assess the risk of metastasis and prognosis of the disease. Lymph node assessment is crucial for the choice of treatment strategy for endometrial cancer, since metastatic lymph node involvement is one of the main factors affecting prognosis. At the same time, the criteria for the appropriateness of lymphadenectomy in low-differentiated malignant tumors are not clearly defined. Various molecular methods have been proposed to assess the status of lymph nodes; candidate genes are being studied as potential diagnostic biomarkers, as well as microRNA. The aim of the study was to analyze the literature data on numerous studies of molecular risk factors for progression in endometrioid carcinoma, as well as to preserve the most important marker changes in relation to the prognostic development of this disease. A literature review was conducted using data from the electronic databases PubMed, Google Scholar, and Wiley Cochrane Library for the period from 2018 to 2023 using the specific keywords. The current scientific genetic studies on metastasis and prognostic factors in uterine cancer were analyzed, and a systematization of the reviewed data from the modern literature was done. To select the most effective treatment - intraoperative, adjuvant or combination therapy, minimize postoperative risks of lymphadenectomy and clearly predict the results - further study of the molecular genetic features of endometrial cancer is necessary.

Advancing Frontiers in Colorectal Cancer: Exploring Novel Insights and Emerging Trends in Research and Therapy

Colorectal cancer, a known form of cancer poses a global health threat. Ongoing studies are actively investigating perspectives and evolving treatments. This review explores the developments in cancer research covering topics such as profiling, microbiome interactions, immunotherapy, precision medicine, tumor environment analysis, liquid biopsies, metabolic changes, artificial intelligence applications and patient centric care. Molecular subtyping advancements have greatly improved our understanding of the nature of cancer and how different individuals respond to therapies. The significant link between gut microbiome composition, inflammation levels and immune responses underscores the importance of interventions targeting the microbiome and innovative immunotherapy strategies. Precision medicine initiatives are leveraging biomarkers and molecular signals to inform treatment decisions and optimize outcomes. This thorough examination highlights the impact of evolving trends in cancer research and treatment strategies while offering insights into directions for improving patient care and results.Keywords: Cancer research; Microbiome interaction; Immunotherapy; Liquid biopsy; Biomarkers

PACAP38 synergizes with irradiation to suppress the proliferation of multiple cancer cells via regulating SOX6/Wnt/β-catenin signaling.

Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 is an endogenous neuropeptide with diverse functions, notably its critical role in inhibiting tumor proliferation. Radiotherapy is an important step in the standard treatment modality of many tumors. Combining radiotherapy with therapeutic agents represents a new and promising trend aimed at enhancing radiation sensitivity and improving tumor treatment efficacy. However, the efficacy of PACAP38 combined with radiotherapy on tumors has not yet been studied. This study aimed to investigate the impact of PACAP38, both independently and in combination with irradiation, on glioma and breast cancer cells, while elucidating the underlying mechanisms involved. We investigated the impact of PACAP38 independently and combined it with irradiation on glioma and breast cancer cells in vitro through cell counting kit-8, clonogenic formation, Edu assays, and in vivo through a xenograft tumor model. We further explored the molecular mechanisms underlying the inhibitory effects of PACAP38 on tumors using RNA sequencing, western blotting assay, immunohistochemistry, and immunofluorescence analysis. Further investigation of gene function and the downstream mechanism was carried out through small interfering RNA and overexpression lentivirus targeting the SRY-related high-mobility group box 6 (SOX6) gene and western blotting assay. Our findings revealed that PACAP38 could effectively synergize with radiation to suppress the proliferation of glioma and breast cancer cells in vivo and in vitro. Molecular studies revealed that the inhibitory effect of PACAP38 on tumor cell proliferation was mediated by upregulating SOX6 protein expression through histone acetylation, thereby inhibiting the Wnt-β-catenin signaling pathway. PACAP38 synergizes with irradiation to suppress the proliferation of multiple cancer cells via regulating SOX6/Wnt/β-catenin signaling. This combination may represent a promising therapeutic strategy for cancer treatment, potentially improving outcomes for patients undergoing radiotherapy.

Advancements of anticancer agents by targeting the Hippo signalling pathway: biological activity, selectivity, docking analysis, and structure-activity relationship.

The Hippo signalling pathway is prominent andgoverns cell proliferation and stem cell activity, acting as a growth regulator and tumour suppressor. Defects in Hippo signalling and hyperactivation of its downstream effector's Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) play roles in cancer development, implying that pharmacological inhibition of YAP and TAZ activity could be an effective cancer treatment strategy. Conversely, YAP and TAZ can also have beneficial effects in promoting tissue repair and regeneration following damage, therefore their activation may be therapeutically effective in certain instances. Recently, a complex network of intracellular and extracellular signalling mechanisms that affect YAP and TAZ activity has been uncovered. The YAP/TAZ-TEAD interaction leads to tumour development and the protein structure of YAP/TAZ-TEAD includes three interfaces and one hydrophobic pocket. There are clinical and preclinical trial drugs available to inhibit the hippo signalling pathway, but these drugs have moderate to severe side effects, so researchers are in search of novel, potent, and selective hippo signalling pathway inhibitors. In this review, we have discussed the hippo pathway in detail, including its structure, activation, and role in cancer. We have also provided the various inhibitors under clinical and preclinical trials, and advancement of small molecules their detailed docking analysis, structure-activity relationship, and biological activity. We anticipate that the current study will be a helpful resource for researchers.

Exploring the Structure-Activity Relationship of COX Inhibitors with Anticancer Effects: A Comprehensive Review.

Cancer is a multifaceted disease with high mortality rates, and current treatments face challenges such as chemoresistance and tumor adaptation. Since Virchow reported the first case of cancer-related chronic inflammation, numerous clinical and epidemiological studies have indicated that around 15-20% of malignant tumors are caused by inflammation. Cyclooxygenase-2 (COX-2), which is the key enzyme in inflammation, has been implicated in tumorigenesis through various mechanisms, including promoting angiogenesis, inhibiting apoptosis, and enhancing the invasiveness of cancer cells. Moreover, COX inhibitors have demonstrated a substantial reduction in death rates associated with esophageal and colon cancer. In this context, targeting COX-2 is an effective strategy for cancer prevention and treatment. This review focuses on the analysis of studies conducted between 2014 and 2024, which evaluate the structure-activity relationship of molecules intended to exhibit cytotoxic activity through COX inhibition. The studies followed both classical and non-classical COX-2 selective drug design strategies. While some focused on the classical approach, utilizing diaryl heterocyclic structures, others explored non-classical designs with a cyclic central scaffold and a linear core. Additionally, several manuscripts employed well-known COX inhibitors, including licofelone, indomethacin, naproxen, tolfenamate, celecoxib, flumizole, and ketoprofen, as starting points for further derivatization and optimization. Cytotoxic activity was evaluated using various cell lines, including MCF- 7, HCT-116, and A549, through assays such as MTT, CellTiter, and MTS. Additionally, studies examined the relationship between COX-2 inhibition and key cancer pathways, including apoptosis and the involvement of enzymes like HDAC, EGFR, and topoisomerase. The majority of studies reported promising cytotoxic activity in COX-2 selective inhibitors. Compounds synthesized with diphenyl heterocyclic scaffolds exhibited enhanced COX-2 selectivity and anticancer efficacy. In particular, derivatives in studies 9, 16, and 24 demonstrated significant activity comparable to standard drugs like celecoxib and doxorubicin. However, only a few studies indicated a weak correlation between COX-2 inhibition and cytotoxicity, suggesting the need for further investigation into other cancer-related mechanisms. This review highlights the potential of COX-2 selective inhibitors in anticancer drug development. The findings support the development of selective COX-2 inhibitors with diverse chemical structures as a promising strategy for cancer therapy.

Atezolizumab plus bevacizumab and chemotherapy versus bevacizumab plus chemotherapy for metastatic cervical cancer: a cost-effectiveness analysis.

The objective of this study is to conduct a cost-effectiveness analysis in order to evaluate the economic advantages of incorporating atezolizumab into a standard bevacizumab plus platinum regimen for the treatment of metastatic cervical cancer from the Chinese medical system perspective. We developed a partitioned survival model based on data obtained from the recently published BEATcc clinical trial and economic cost data. Our model utilized a tree-based decision analysis approach to simulate two different treatment strategies for metastatic cervical cancer: the standard bevacizumab plus platinum regimen, and the addition of atezolizumab to the standard treatment regimen. The economic assessment data included the costs of the drugs, costs related to treatment-induced adverse events. The cost-effectiveness metrics used in the analysis were quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER). The robustness of our model was assessed through sensitivity analysis. The total costs of the atezolizumab group were $128179.56, while the costs of chemotherapy group were $42065.89. The atezolizumab group gained 3.52 QALYs, whereas the chemotherapy group gained 2.35 QALY. The atezolizumab regimen resulted in an increase of 1.17 QALYs at an incremental cost of $86113.67. This led to an ICER of $73601.43, which exceeds the willingness-to-pay (WTP) threshold of $39855.79 in China. Sensitivity analysis demonstrated none of the parameters within a margin of ±25% result in significant alterations to the analysis findings. Atezolizumab plus bevacizumab and chemotherapy was not to be a cost-effective option for the treatment of metastatic cervical cancer compared to bevacizumab plus chemotherapy.

Colorectal Cancer and Its Microenvironment: A Brief Review.

The narrative review aims to explore CRC pathogenesis by deciphering genetic-environmental interactions, analyzing the tumor microenvironment's role, and assessing treatment responses. These objectives seek to enhance clinical decision-making and improve CRC patient care through a comprehensive understanding of the disease. A narrative review from 2019 to 2024 on colorectal cancer (CRC) pathogenesis and treatment strategies was conducted. Systematic literature searches were performed on PubMed, using CRC-related keywords ("Colorectal Neoplasms"[Mesh]) AND "Tumor Microenvironment"[Mesh]. Screening yielded 233 eligible studies, with 14 highly relevant ones included. PRISMA guidelines were followed for transparency and reproducibility. This narrative review spanning 2019-2024 shows diverse study designs (5 clinical studies, 4 randomized controlled trials, 2 cohort studies, and 3 systematic literature reviews) with varied sample sizes (from 14 to 4000 participants). Genetic mutations like KRAS and BRAF are significant in colorectal cancer pathogenesis, with 8% exhibiting MMR proficiency. Immune cells and paracrine signaling are influential, and therapeutic responses vary, with limited efficacy reported in certain combinations. This narrative review highlights CRC's multifactorial nature and complex tumor dynamics. Integrating genetic, environmental, and immune factors, personalized therapies are pivotal for efficacy. Continued research is crucial for optimizing treatments and improving patient outcomes, emphasizing the need for multifaceted, patient-tailored approaches in CRC management.

Research and Progress on the Association of Porphyromonas gingivalis with Lung Cancer

Porphyromonas gingivalis is a key pathogenic microorganism that triggers periodontitis. It is closely associated with oral diseases such as chronic periodontitis and recently found to have a significant correlation with the occurrence, progression, and prognosis of cancer. As the leading malignant tumor in terms of both incidence and mortality worldwide, lung cancer has always been a focus and hotspot of research. The causes of lung cancer are complex and involve multiple factors, including smoking, occupational factors, air pollution, ionizing radiation, diet and nutrition, genetic factors, etc. Researchers have also begun to pay attention to the relationship between oral microbiota and overall health, especially the link with lung cancer. The article summarizes the latest advancements in research on Porphyromonas gingivalis in lung cancer, primarily encompassing etiology and pathogenic mechanisms, and explores its potential as a therapeutic target for lung cancer, aiming to provide new insights and directions for lung cancer prevention and treatment strategies. .

Exploring Neighborhood-Level Environmental Justice to Tackle County-Level Disparities in Breast Cancer Outcomes

Breast cancer is a disease in which cells, originating from the breast epithelium, grow out of control and form tumors. The progression of breast cancer can vary, and its severity is often categorized by stages ranging from early, localized forms to more advanced stages involving widespread dissemination. Breast cancer cases can be hereditary or non-hereditary; Hereditary cases are caused by a penetrant gene mutation: one that is pathogenic and has the potential to promote the development of cancer whereas non-hereditary cases can be caused by a variety of day-to-day exposures affected by socioeconomic disparities and health literacy rates. Despite scientific and technological advancements, researchers and health officials still do not know enough about the disease and breast cancer incidence rates in the United States have steadily increased. This literature review aims to synthesize the relationship between breast cancer health outcomes and environmental justice, health literacy, and socioeconomic disparities. This relationship was first examined from a county-level in the state of Florida. We first examined three Florida counties with varying socioeconomic profiles (Broward, Miami-Dade, and Palm Beach) and then examined neighborhoods within the county of Miami-Dade (selected because it has the highest breast cancer rates out of all Florida counties). This examination revealed higher incidences of breast cancer in Latinx and African American communities with high environmental exposures and lower socioeconomic statuses. The identification of specific neighborhoods primarily affected by environmental exposures and low socioeconomic statuses emphasizes the need for neighborhood level modeling to inform future breast cancer research and intervention strategies.

Interferon gamma-gaillardin nanocomplex formation with improved anti-melanoma effects

This study presents a comprehensive analysis of IFN-γ-Gaillardin nanoparticles (NPs) using a combination of computational, biophysical and cell-based approaches. The molecular docking analysis revealed that both hydrogen and hydrophobic forces are involved in the formation of IFN-γ-Gaillardin complex The interaction between IFN-γ and Gaillardin was further characterized by a pronounced ANS fluorescence spectrum peak and a higher intensity for IFN-γ. The Langmuir, Scatchard, and Hill analyses revealed a higher affinity and lower dissociation constant for IFN-γ NPs compared to IFN-γ alone, suggesting enhanced complex stability. Thermal gravimetric analysis confirmed that the Gaillardin interaction might improve the thermal stability of the NPs. The NPs demonstrated robust stability in various media, highlighting their potential as a delivery system. However, size increase in deionized water suggests the need for formulation optimization. Cell-based assays revealed selective cytotoxicity towards A-375 melanoma cancer cells with minimal impact on non-cancerous HaCaT cells, indicating targeted antitumor effects. Real-time PCR showed gene expression changes consistent with antitumor activity and immune response modulation. The findings suggest that IFN-γ-Gaillardin NPs have potent antitumor properties and the ability to modulate the immune system, warranting further investigation into their therapeutic applications. The development of an IFN-γ-based nanocarrier system for Gaillardin delivery offers a promising approach to melanoma therapy, setting a new direction for NP-based cancer treatment strategies.

Nanomedicine for cancer patient-centered care.

Cancer is a leading cause of morbidity and mortality worldwide, and an increase in incidence is estimated in the next future, due to population aging, which requires the development of highly tolerable and low-toxicity cancer treatment strategies. The use of nanotechnology to tailor treatments according to the genetic and immunophenotypic characteristics of a patient's tumor, and to allow its targeted release, can meet this need, improving the efficacy of treatment and minimizing side effects. Nanomedicine-based approach for the diagnosis and treatment of cancer is a rapidly evolving field. Several nanoformulations are currently in clinical trials, and some have been approved and marketed. However, their large-scale production and use are still hindered by an in-depth debate involving ethics, intellectual property, safety and health concerns, technical issues, and costs. Here, we survey the key approaches, with specific reference to organ-on chip technology, and cutting-edge tools, such as CRISPR/Cas9 genome editing, through which nanosystems can meet the needs for personalized diagnostics and therapy in cancer patients. An update is provided on the nanopharmaceuticals approved and marketed for cancer therapy and those currently undergoing clinical trials. Finally, we discuss the emerging avenues in the field and the challenges to be overcome for the transfer of nano-based precision oncology into clinical daily life.

Stem cell research and improving cancer treatments

Stem cell research has emerged as a pivotal area in oncology, offering innovative approaches to cancer treatment. This research explores the potential of stem cells to enhance therapeutic outcomes in various cancer types. To evaluate the role of stem cells in cancer treatment, focusing on their ability to differentiate into specialized cell types, promote tissue regeneration, and deliver targeted therapies. A comprehensive review of current literature was conducted, analyzing studies that investigate the application of stem cells in hematological malignancies and solid tumors. Key methodologies included in vitro experiments, animal models, and clinical trials assessing stem cell therapies, including hematopoietic stem cell transplantation and mesenchymal stem cell-based therapies. Findings indicate that stem cells can improve treatment efficacy by facilitating tumor regression, enhancing immune responses, and reducing treatment-related toxicity. Notably, mesenchymal stem cells have shown promise in delivering therapeutic agents directly to tumors and modulating the tumor microenvironment. Stem cell research holds significant potential to revolutionize cancer treatment strategies. Continued exploration of stem cell applications may lead to more effective, personalized therapies, ultimately improving patient outcomes in various cancer types. Further clinical trials are necessary to establish standardized protocols and assess long term effects.

Progressive cancer targeting by programmable aptamer-tethered nanostructures.

Scientific research in recent decades has affirmed an increase in cancer incidence as a cause of death globally. Cancer can be considered a plurality of various diseases rather than a single disease, which can be a multifaceted problem. Hence, cancer therapy techniques acquired more accelerated and urgent approvals compared to other therapeutic approaches. Radiotherapy, chemotherapy, immunotherapy, and surgery have been widely adopted as routine cancer treatment strategies to suppress disease progression and metastasis. These therapeutic approaches have lengthened the longevity of countless cancer patients. Nonetheless, some inherent limitations have restricted their application, including insignificant therapeutic efficacy, toxicity, negligible targeting, non-specific distribution, and multidrug resistance. The development of therapeutic oligomer nanoconstructs with the advantages of chemical solid-phase synthesis, programmable design, and precise adjustment is crucial for advancing smart targeted drug nanocarriers. This review focuses on the significance of the different aptamer-assembled nanoconstructs as multifunctional nucleic acid oligomeric nanoskeletons in efficient drug delivery. We discuss recent advancements in the design and utilization of aptamer-tethered nanostructures to enhance the efficacy of cancer treatment. Valuably, this comprehensive review highlights self-assembled aptamers as the exceptionally intelligent nano-biomaterials for targeted drug delivery based on their superior stability, high specificity, excellent recoverability, inherent biocompatibility, and versatile functions.

EGCG targeting STAT3 transcriptionally represses PLXNC1 to inhibit M2 polarization mediated by gastric cancer cell-derived exosomal miR-92b-5p

M2-polarized tumor-associated macrophages (TAMs) predominate in tumor microenvironment (TME) and serve primary functions in tumor progression, including growth, angiogenesis, metastasis, immunosuppression, chemoresistance, and poor prognosis. The reversal of M2 polarization provides a new treatment strategy for cancer. Presently, the molecular mechanisms of M2 polarization have yet to be fully characterized, and there is a lack of effective therapeutic targets and drugs. Cancer cells initiate an immunosuppressive TME by recruiting macrophages and promoting M2 polarization through the secretion of inflammatory factors. Accordingly, blocking cancer cell-induced TAM M2 polarization may present a more effective strategy from the perspective of cancer cells. Hedyotis diffusa Willd (HDW) possesses immunomodulatory and antitumor properties, and is a precious and direct source of small molecule natural products with a dual function of inhibition of tumor growth and tumor cell-mediated M2 polarization. To identify a new target promoting gastric cancer (GC) cell growth and GC cell-mediated M2 polarization from mRNA profiles of GC cells treated with HDW injection (HDI) and to excavate a natural product from HDI that can regulate related mRNA and inhibit the aforementioned effects. RNA sequencing (RNA-seq) was used to analyze HDI-regulated differentially expressed mRNAs (HRmRNAs) in MKN45 cells. Weighted gene co-expression network analysis (WGCNA), univariate and multivariate Cox regression analysis, KM survival curves, and association analysis between HRmRNA and clinical characteristics/tumor infiltrating immune cells (TIICs) individually were utilized to screen out the target HRmRNA associated with prognosis and M2 macrophage infiltration in GC. shRNA lentiviral vectors were used for stably silencing, and transient overexpressing plasmids were constructed for overexpression. CCK8, EdU, colony formation, migration and invasion assays were used to validate the function of drugs and molecules in GC. HDI constituent analysis was performed using UHPLC-QE-MS. A network of HDI constituent-hub transcription factor (TF)-HRmRNA was constructed based on RNA-Seq, network pharmacology and TFs prediction. Exosome isolation and identification were performed using ultracentrifugation, NTA, TEM and western blot. Apoptosis and macrophage phenotypes were determined by flow cytometric analysis. Small RNA-Seq made exosomal miRNA identification. Small molecule interaction with targets were analyzed using molecular docking, SPR and CETSA. The direct relationship between transcription factors and promoters was verified using ChIP-QPCR and dual-luciferase reporter gene assay. A nude mice xenograft tumor model was established for vivo validation. HDI inhibited MKN45 cell proliferation, migration, invasion and promoted apoptosis. RNA-Seq identified 2583 HRmRNAs. PLXNC1 was screened out as the target HRmRNA associated with prognosis and M2 macrophage infiltration in GC. PLXNC1 promoted GC cell proliferation and facilitated TAMs M2 polarization by transferring GC cell-derived exosomal miR-92b-5p, inhibiting SOCS7-STAT3 interactions and subsequently activating STAT3 in macrophages. M2 TAMs induced by PLXNC1-mediated GC cell-derived exosomes promoted GC cell migration and invasion. PLXNC1 regulated exosomal miR-92b-5p through the MEK1/MSK1/CREB1 pathway. STAT3 could transcriptionally regulate PLXNC1 expression in GC cells. The network of HDI constituent-hub TF-HRmRNA showed epigallocatechin gallate (EGCG) from HDI targeted STAT3 to transcriptionally regulate PLXNC1 expression. EGCG as a natural product directly bound to STAT3 to diminish its nuclear localization, resulting in the transcriptional repression of PLXNC1 and the reversal of M2 polarization induced by PLXNC1-mediated GC cell-derived exosomes. PLXNC1 is a novel target exerting dual effects on GC cell proliferation and GC cell-mediated M2 polarization. EGCG derived from HDI inhibits GC cell proliferation and targets STAT3 to inhibit M2 polarization induced by PLXNC1-mediated exosomes derived from GC cells, which may be a multi-target therapeutic agent for GC cell proliferation and immune microenvironment.

Feasibility of neoadjuvant chemotherapy for bulky early stage to stage IIIB cervical cancer in Uganda

IntroductionExternal beam radiotherapy (EBRT) became unavailable in Uganda from February 2016 to November 2017. Following resource stratification guidelines, an alternative treatment strategy was developed. MethodsBulky early stage to Stage IIIB patients received at least 3 cycles of neoadjuvant chemotherapy (NAC). Surgery was performed if adequate response was achieved and adjuvant therapy given for high risk factors. Chemotherapy versus supportive care was advised in unresectable disease. NAC protocol completion was defined as receiving at least 3 cycles of NAC followed by either surgery, chemotherapy and/or radiation, or best supportive care. The purpose of this study was to determine the completion rate of NAC and assess the adverse events associated with treatment. Data were collected through retrospective chart review. ResultsFrom February 2016 to November 2018, 53 evaluable patients were identified. 86.8% (46/53) of patients presented in Stage IIB or higher. The completion rate of the NAC protocol was 75.5% (40/53). 94.3% (50/53) received platinum-taxane combination. 7.6% (4/52) grade 3 adverse events occurred related to chemotherapy, all hematologic. 18.8% (10/53) patients underwent surgery with 2 aborted cases due to metastatic or inoperable disease. No adverse events related to surgery were reported. 5 patients underwent adjuvant therapy after surgery due to high risk factors or incomplete pathology findings. 26 patients received adjuvant radiation (3 brachytherapy, 23 EBRT after it became available). Reported side effects related to radiation included vaginal fibrosis and skin reactions. ConclusionIn this limited-resource setting, majority of patients completed a NAC treatment strategy for cervical cancer with acceptable toxicities.

Metal‐organic frameworks‐based nanomedicines to promote cancer immunotherapy: Recent advances and future directions

AbstractCancer immunotherapy uses the body's immune system to fight tumors by restoring natural antitumor responses. Metal‐organic frameworks (MOFs), characterized by their unique crystalline porous structures formed from metal ions linked by organic ligands, offer a promising solution. Recent studies have unveiled the potential of MOFs in cancer immunotherapy. The exceptional porosity and surface area, coupled with their extraordinary thermal and chemical stability, bring significant advantages for efficient drug loading and delivery of immunotherapeutic agents. The adaptability of MOFs further enhances the controlled release of immunotherapeutic drugs within target cells and increases tumor sensitivity to other therapies such as photodynamic, photothermal, and radiotherapy. This multifunctional carrier contributes to modulating the tumor microenvironment and reactivating antitumor immunity, providing a comprehensive strategy for cancer treatment. In this review, we summarize the applications of MOFs in immune checkpoint blockade, immunomodulator delivery, and cancer vaccine delivery, and discuss existing challenges in their use for immunotherapy. This discussion aims to offer insights for developing better treatments and enhancing the efficacy of immunotherapy.

Machine learning-assisted identification of potential cancer inhibitors: Multifunctional biomineralized CaCO3-polyethyleneimine nanoparticle carriers and their application in lung cancer therapy

Cancer, as a prevalent phenomenon among malignant tumors, has a late-stage diagnosis rate approaching half, significantly limiting treatment efficacy and imposing substantial physiological and psychological burdens on patients. Therefore, developing innovative therapeutic platforms that simultaneously optimize diagnostic accuracy, enhance therapeutic efficacy, and minimize side effects is a critical scientific challenge in the field of precision cancer medicine. In this study, we employed a simple and efficient one-pot synthesis method combined with polyethyleneimine (PEI)-mediated biomineralization technology to successfully prepare calcium carbonate-polyethyleneimine (CaCO3-PEI) composite nanoparticles. These nanoparticles exhibit high pH sensitivity and can rapidly degrade under the mildly acidic conditions that mimic the tumor microenvironment, providing potential for targeted tumor therapy. Subsequently, we encapsulated compound 1, which has potential for lung cancer treatment, within the CaCO3-PEI nanoparticles, successfully constructing the CaCO3-PEI@1 composite system. Structural analysis of this composite system was conducted through characterization techniques. In vitro cell experiments demonstrated that the CaCO3-PEI@1 composite system exhibited significant anticancer effects by effectively inhibiting cancer cell proliferation through the regulation of apoptosis-related protein Bax expression. This provides new insights and experimental evidence for the development of cancer treatment strategies. Based on the experiment and molecular docking identified activity against lung cancer, the compound 1 was used as the initiator for the machine learning model, and up to 10,000 episodes were generated, after thorough examination, it was found about two-thirds of the generated episodes were entirely different from each other, which demonstrated that the machine learning model was a powerful tool for designing of potential inhibitors against lung cancer.

A multifunctional nanosystem catalyzed by cascading natural glucose oxidase and Fe3O4 nanozymes for synergistic chemodynamic and photodynamic cancer therapy

The significance of the tumor microenvironment (TME) in tumor initiation and progression is increasingly acknowledged. Conventional therapeutic approaches face limitations within the complex TME, including the restrictions imposed by hypoxia on photodynamic therapy (PDT) and the deficiency of endogenous H₂O₂ affecting chemodynamic therapy (CDT). In response to the TME's characteristics of high metabolism, hypoxia, and weak acidity, a multifunctional nanosystem MNPs/GOD@CS/IR820, which synergistically integrates CDT and PDT, has been developed. This system can actively accumulate at tumor sites under an external magnetic field and release active components in response to the weakly acidic TME. It mitigates the limitations imposed by hypoxia and endogenous H₂O₂ deficiency on PDT and CDT, respectively, thereby enabling synergistic treatment. Additionally, the system's multimodal imaging capabilities facilitate precise tumor localization and real-time, non-invasive in vivo assessment via fluorescence imaging and MRI. In vitro and in vivo evaluations demonstrate significant antitumor efficacy, effectively inhibiting tumor growth and improving survival rates. By comprehensively addressing the challenges posed by the complex TME and enhancing real-time monitoring capabilities, our nanosystem paves the way for personalized and precise cancer treatment. Statement of significanceThis study introduces an innovative MNPs/GOD@CS/IR820 nanosystem that represents a significant advancement in cancer nanomedicine by addressing critical limitations of conventional photodynamic therapy (PDT), particularly in hypoxic tumor microenvironments. By synergistically integrating chemodynamic therapy (CDT) with PDT and incorporating MRI and fluorescence dual-modal imaging capabilities, this multifunctional platform offers enhanced therapeutic efficacy and real-time monitoring. The system's ability to generate oxygen in situ overcomes hypoxia-induced limitations, while its multimodal mechanism of action induces tumor cell apoptosis through multiple pathways. In vitro and in vivo studies demonstrate remarkable antitumor efficacy across diverse cancer types, significantly inhibiting tumor growth and improving survival rates. This comprehensive approach to cancer diagnosis and treatment not only advances precision medicine for targeted, multimodal cancer management but also provides a promising foundation for future clinical applications, potentially transforming cancer treatment strategies and improving patient outcomes.

Harnessing Gene Editing Technology for Tumor Microenvironment Modulation: An Emerging Anticancer Strategy.

Cancer is a multifaceted disease influenced by both intrinsic cellular traits and extrinsic factors, with the tumor microenvironment (TME) being crucial for cancer progression. To satisfy their high proliferation and aggressiveness, cancer cells always plunder large amounts of nutrients and release various signals to their surroundings, forming a dynamic TME with special metabolic, immune, microbial and physical characteristics. Due to the neglect of interactions between tumor cells and the TME, traditional cancer therapies often struggle with challenges such as drug resistance, low efficacy, and recurrence. Importantly, the development of gene editing technologies, particularly the CRISPR-Cas system, offers promising new strategies for cancer treatment. Combined with nanomaterial strategies, CRISPR-Cas technology exhibits precision, affordability, and user-friendliness with reduced side effects, which holds great promise for profoundly altering the TME at the genetic level, potentially leading to lasting anticancer outcomes. This review will delve into how CRISPR-Cas can be leveraged to manipulate the TME, examining its potential as a transformative anticancer therapy.

The Microbial Sources of Bioactive Compounds: Potential Anticancer Therapeutic Options

Chemotherapy and other traditional anticancer treatments are losing their efficacy in the battle against cancer. As a result, cancer treatment strategies must be continually adjusted to meet the rising demand for alternative medicines. Several viral and non-viral vectors have been used previously. However, it has been shown that microorganisms are a strong contender for successfully combating cancer. They are a remarkable source of toxins, polysaccharides, tumor-specific anticancer genes, nanodrugs and gene-delivery vectors. One of the emerging key players in cancer therapy is bacteria. It has been demonstrated that traditional methods of altering the microbiome, such as antibiotics, probiotics and microbiota transplants, can sometimes increase the effectiveness of cancer therapies. However, problems with these methods, such as consistency and collateral damage to the commensal microbiota, spur the development of new technologies specifically aimed at the microbiome-cancer interface. In light of nanotechnology’s success in transforming cancer diagnostics and treatment, nanotechnologies with the capacity to control interactions that occur across microscopic and molecular length scales in the microbiome and the tumor microenvironment have the potential to provide innovative methods for cancer treatment. The relationship between nanotechnology, the microbiome and cancer offers tremendous potential. This paper highlights the contributions of significant bacterial groups to several anticancer research fields.