Spread Of Cancer Research Articles

E2F1 activates breast stromal fibroblasts and promotes their paracrine pro-carcinogenic effects

Breast cancers (BC) are complex neo-organs composed of neoplastic as well as non-carcinogenic cells, in addition to a dynamic extracellular matrix. Active cancer-associated fibroblasts (CAFs) play major roles in the development and spread of breast cancers, through paracrine signaling, which are under the control of several transcription regulators. In the present study, we investigated the role of the transcription factor E2F1 in the active status of CAFs. We have shown that CAFs express higher levels of E2F1 compared to their adjacent tumor counterpart fibroblasts (TCFs). Importantly, E2F1 upregulation by ectopic expression transactivated quiescent breast stromal fibroblasts and promoted their paracrine pro-carcinogenic effects. Indeed, E2F1-expressing fibroblasts were more efficient than their corresponding controls in enhancing the epithelial-to-mesenchymal transition and stemness processes in breast cancer cells both in vitro and in vivo. However, E2F1 knock-down normalized breast CAFs and suppressed their paracrine pro-carcinogenic effects. Interestingly, while fibroblasts expressing high level of E2F1 enhanced the resistance of BC cells to chemotherapeutic drugs, E2F1-deficient fibroblasts enhanced their sensitivity to cisplatin. Together, these findings indicate that the transciption factor E2F1 plays a critical role in the transactivation of breast stromal fibroblasts, and therefore could be a great therapeutic target for precision therapeutics of BC patients.

Breaking up clusters of circulating tumour cells to halt cancer spread

Breaking up clusters of circulating tumour cells to halt cancer spread

Identifying Primary Sites of Spinal Metastases: Expert-Derived Features vs. ResNet50 Model Using Nonenhanced MRI.

The spinal column is a frequent site for metastases, affecting over 30% of solid tumor patients. Identifying the primary tumor is essential for guiding clinical decisions but often requires resource-intensive diagnostics. To develop and validate artificial intelligence (AI) models using noncontrast MRI to identify primary sites of spinal metastases, aiming to enhance diagnostic efficiency. Retrospective. A total of 514 patients with pathologically confirmed spinal metastases (mean age, 59.3 ± 11.2 years; 294 males) were included, split into a development set (360) and a test set (154). Noncontrast sagittal MRI sequences (T1-weighted, T2-weighted, and fat-suppressed T2) were acquired using 1.5 T and 3 T scanners. Two models were evaluated for identifying primary sites of spinal metastases: the expert-derived features (EDF) model using radiologist-identified imaging features and a ResNet50-based deep learning (DL) model trained on noncontrast MRI. Performance was assessed using accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve (ROC-AUC) for top-1, top-2, and top-3 indicators. Statistical analyses included Shapiro-Wilk, t tests, Mann-Whitney U test, and chi-squared tests. ROC-AUCs were compared via DeLong tests, with 95% confidence intervals from 1000 bootstrap replications and significance at P < 0.05. The EDF model outperformed the DL model in top-3 accuracy (0.88 vs. 0.69) and AUC (0.80 vs. 0.71). Subgroup analysis showed superior EDF performance for common sites like lung and kidney (e.g., kidney F1: 0.94 vs. 0.76), while the DL model had higher recall for rare sites like thyroid (0.80 vs. 0.20). SHapley Additive exPlanations (SHAP) analysis identified sex (SHAP: -0.57 to 0.68), age (-0.48 to 0.98), T1WI signal intensity (-0.29 to 0.72), and pathological fractures (-0.76 to 0.25) as key features. AI techniques using noncontrast MRI improve diagnostic efficiency for spinal metastases. The EDF model outperformed the DL model, showing greater clinical potential. Spinal metastases, or cancer spreading to the spine, are common in patients with advanced cancer, often requiring extensive tests to determine the original tumor site. Our study explored whether artificial intelligence could make this process faster and more accurate using noncontrast MRI scans. We tested two methods: one based on radiologists' expertise in identifying imaging features and another using a deep learning model trained to analyze MRI images. The expert-based method was more reliable, correctly identifying the tumor site in 88% of cases when considering the top three likely diagnoses. This approach may help doctors reduce diagnostic time and improve patient care. 3 TECHNICAL EFFICACY: Stage 2.

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer

BackgroundThe best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.MethodsIn this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.4 Gy and carboplatin and paclitaxel) plus surgery. Eligibility criteria included a primary tumor with a clinical stage of cT1 cN+, cT2–4a cN+, or cT2–4a cN0 disease, in which T indicates the size and extent of the tumor (higher numbers indicate a more advanced tumor), and N indicates the presence (N+) or absence (N0) of cancer spread to the lymph nodes, without evidence of metastatic spread. The primary end point was overall survival.ResultsFrom February 2016 through April 2020, we assigned 221 patients to the FLOT group and 217 patients to the preoperative-chemoradiotherapy group. With a median follow-up of 55 months, overall survival at 3 years was 57.4% (95% confidence interval [CI], 50.1 to 64.0) in the FLOT group and 50.7% (95% CI, 43.5 to 57.5) in the preoperative-chemoradiotherapy group (hazard ratio for death, 0.70; 95% CI, 0.53 to 0.92; P=0.01). Progression-free survival at 3 years was 51.6% (95% CI, 44.3 to 58.4) in the FLOT group and 35.0% (95% CI, 28.4 to 41.7) in the preoperative-chemoradiotherapy group (hazard ratio for disease progression or death, 0.66; 95% CI, 0.51 to 0.85). Among the patients who started the assigned treatment, grade 3 or higher adverse events were observed in 120 of 207 patients (58.0%) in the FLOT group and in 98 of 196 patients (50.0%) in the preoperative-chemoradiotherapy group. Serious adverse events were observed in 98 of 207 patients (47.3%) in the FLOT group and in 82 of 196 patients (41.8%) in the preoperative-chemoradiotherapy group. Mortality at 90 days after surgery was 3.1% in the FLOT group and 5.6% in the preoperative-chemoradiotherapy group.ConclusionsPerioperative chemotherapy with FLOT led to improved survival among patients with resectable esophageal adenocarcinoma as compared with preoperative chemoradiotherapy. (Funded by the German Research Foundation; ESOPEC ClinicalTrials.gov number, NCT02509286.)

TNF-α polymorphism in oral cancer and oral potentially malignant disorders: meta-analysis and investigation as a potential tool to determine individual susceptibility and the prognosis.

There is increasing evidence that tumour necrosis factor alpha (TNF-α) gene polymorphisms may promote development and spread of cancer through transitions at different loci that lead to its altered expression. However, data on TNF-α gene polymorphisms in oral cancer remain highly controversial. This meta-analysis was performed to determine the impact of TNF-α gene polymorphisms on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). An electronic search was conducted in the PubMed, Cochrane Library, Google Scholar, and Web of Science databasesto identify original articles reporting TNF-α polymorphism in OSCC and OPMD. The articles were examined by two independent authors. Data from the included articles were compiled and tabulated. Risk of bias was analysed. Overall, 11 eligible articles that included 1070 cases of OSCC and 641 cases of OPMD in which TNF-α polymorphism was studied, were included for quantitative analysis. It was found that both TNF-α -308 and -238 polymorphisms were significantly associated with the development of oral cancer. TNF-α polymorphism was significantly associated with OSCC and OPMD. Moreover, in polymorphisms of TNF-α at both -308 and -238, the G allele, especially the homozygous form (GG), was found to be associated with oral cancer.

Ketogenic diet and cancer: multidimensional exploration and research.

The ketogenic diet (KD) has attracted attention in recent years for its potential anticancer effects. KD is a dietary structure of high fat, moderate protein, and extremely low carbohydrate content. Originally introduced as a treatment for epilepsy, KD has been widely applied in weight loss programs and the management of metabolic diseases. Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells, thereby inhibiting tumor angiogenesis, reducing oxidative stress in normal cells, and affecting cancer cell signaling and other processes. Moreover, KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota, enhance the efficacy of standard cancer treatments, and mitigate the complications of chemotherapy. However, controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer. Therefore, this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.

MircoRNAs predict and modulate responses to chemotherapy in leukemic patients.

Leukemia covers a broad category of cancer malignancies that specifically affect bone marrow and blood cells. While different kinds of leukemia have been identified, effective treatments are still lacking for most forms, and even those treatments considered effective can lead to relapses. MicroRNAs, or miRNAs, are short endogenous non-coding single-stranded RNAs that help control the epigenetics of gene expression. Recently, a literature review proposed that miRNAs provided promising therapeutic targets for patients diagnosed with leukemia. Due to genetic abnormalities occurring during the maturation of white blood cells, studies commonly observed uncontrolled replication and decreased cell death, compared to healthy cells. This results in the activation of oncogenes, deactivation of tumor suppressor genes, and disruption of normal cellular functions. Although conventional cancer treatments significantly contribute to patient recovery, they can also impose many side effects. MiRNAs all significantly regulate angiogenesis, migration, apoptosis, carcinogenesis, and gene expression. Regarding chemotherapy, mounting research indicates that microRNAs may directly influence how responsive leukemia is to chemical treatments. This article reviews current studies on microRNAs, examining their influence on cancer advancement and spread, as well as their possible applications as diagnostic indicators and treatment targets in leukemia. Furthermore, we integrated the functions of microRNAs in cancer formation and progression with leukemia patient care, offering fresh insights into leukemia detection and management strategies.

Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.

Ubiquitination is cells' second most abundant posttranslational protein modification after phosphorylation. The ubiquitin-proteasome system (UPS) is critical in maintaining essential life processes such as cell cycle control, DNA damage repair, and apoptosis. Mutations in ubiquitination pathway genes are strongly linked to the development and spread of multiple cancers since several of the UPS family members possess oncogenic or tumor suppressor activities. This comprehensive review delves into understanding the ubiquitin code, shedding light on its role in cancer cell biology and immune evasion. Furthermore, we highlighted recent advances in the field for targeting the UPS pathway members for effective therapeutic intervention against human cancers. We also discussed the recent update on small-molecule inhibitors and PROTACs and their progress in preclinical and clinical trials.

Research hotspots and trends in lung cancer STAS: a bibliometric and visualization analysis.

This study employed the R software bibliometrix and the visualization tools CiteSpace and VOSviewer to conduct a bibliometric analysis of literature on lung cancer spread through air spaces (STAS) published since 2015. On September 1, 2024, a computer-based search was performed in the Web of Science (WOS) Core Collection dataset for literature on lung cancer STAS published between January 1, 2015, and August 31, 2024. VOSviewer was used to visually analyze countries, institutions, authors, co-cited authors, and keywords, while CiteSpace was utilized to analyze institutional centrality, references, keyword bursts, and co-citation literature. Descriptive analysis tables were created using Excel 2021. A total of 243 articles were included from the WOS, with a significant increase in annual publications observed since 2018. China, Kadota K, and Fudan University were leading countries, authors, and institutions by publication volume. The top three authors by co-citation count were Kadota K, Chen C, and Adusumilli PS. The journal with the highest publication volume was Lung Cancer, with the most influential journal among the top 10 being the Journal of Thoracic Oncology. The most frequently cited reference was "Lobectomy Is Associated with Better Outcomes than Sublobar Resection in Spread through Air Spaces (STAS)-Positive T1 Lung Adenocarcinoma: A Propensity Score-Matched Analysis." Keyword clustering categorized the research into four main areas: pathological studies of lung cancer STAS, biological mechanisms, prognostic assessment, and imaging analysis. Current research hotspots include deep learning, lung squamous cell carcinoma, and air spaces STAS. The current research on lung cancer STAS primarily focuses on pathological studies, biological mechanisms, prognostic assessments, and preoperative imaging model predictions. This study's findings provide new insights and directions for future research in this area. https://www.crd.york.ac.uk/prospero/#myprospero, identifier 589442.

Protein molecular structures of USP53, NPY2R, and DCTN1-AS1 and impact on tumors: Analysis of prognostic biomarkers for diffuse large B-cell lymphoma.

In the past few years, three protein molecules-USP53, NPY2R, and DCTN1-AS1-have garnered significant attention in scientific research due to their potential implications in tumor development. Mass spectrometry and proteomics techniques were used to analyze the three-dimensional structure of these protein molecules and predict their active sites and functional domains. The effects of USP53, NPY2R and DCTN1-AS1 on biological behavior of tumor cells were studied by constructing gene knockout and overexpression cell models. The data showed that when USP53 was overexpressed, there was a notable enhancement in both the proliferation and invasion capabilities of tumor cells, indicating its potential role in promoting cancer aggressiveness. Conversely, the knockout of USP53 resulted in a significant reduction of these capabilities, highlighting its importance in tumor cell behavior. Similarly, the overexpression of NPY2R correlated with an increased apoptosis rate among tumor cells, suggesting that this protein may play a role in regulating cell survival. On the other hand, the knockout of DCTN1-AS1 markedly diminished the metastatic ability of the tumor cells, emphasizing its potential involvement in cancer spread. Furthermore, the analysis of clinical data provided compelling evidence that high levels of USP53 and NPY2R expression are closely linked to a poor prognosis for patients, suggesting that these proteins could serve as negative prognostic indicators. In contrast, low levels of DCTN1-AS1 expression were found to predict a poor response to treatment, further underscoring its importance in the context of therapy outcomes.

Studying the role of thrombomodulin-plasminogen interaction in spatial and interfacial invasion of melanoma metastatic progression

Thrombomodulin (TM), a transmembrane glycoprotein, has emerged as a key factor in the metastatic spread of various cancers, including malignant melanoma. Despite its recognized significance, the underlying mechanisms of TM's involvement in enhancing metastasis remain incompletely understood. This study addresses this knowledge gap by utilizing spatial and interfacial invasion models in vitro to investigate the effect of the interaction between TM and plasminogen (Plg) on melanoma invasion. While it is well established that Plg induces a chain reaction in the plasmin system, leading to the activation of metalloproteases that promote tumor cell invasion and metastasis, this study is the first to demonstrate that TM binding to Plg can enhance these activations in spatial and interfacial invasion models in vitro. These results highlight the potential of TM as a crucial target for the development of drugs aimed at significantly inhibiting melanoma metastasis and improving patient survival.

Cell specific mitochondria targeted metabolic alteration for precision medicine.

Mitochondria play important roles in the maintenance of cellular health. In cancer, these dynamic organelles undergo significant changes in terms of membrane hyperpolarization, altered metabolic functions, fusion-fission balance, and several other parameters. These alterations promote cancer growth, proliferation and spread, and the eventual development of metastatic disease and therapeutic resistance. Thus, routing therapeutics to the mitochondrial compartments can be one of the most promising methodologies for tackling such changes to achieve cancer control. Over the last decade, targeted cancer medicine has experienced tremendous growth, enabling the targeting of mitochondria for greater therapeutic specificity. Here, we demonstrate a feasibility method to specifically target the mitochondria of prostate cancer cells. We achieve such dual targeting by utilizing two functionalized polymers and constructing a single blended nanoparticle (NP). Such a targeting strategy was developed utilizing a polymeric platform that differed in terms of the length of the amphiphilic portions, the linker between the hydrophobic portions, and the attached targeting moieties. In doing this, we demonstrate prostate cancer specific mitochondrial delivery of a chemotherapeutic prodrug to create repair-resistant adducts within mitochondrial DNA promoting cellular death. This article documents the synthetic strategy, optimization of blended NPs for cell specific mitochondria targeting, and the utility of the proof-of-concept design was demonstrated using a combination of analytical and in vitro studies.

Punctuational evolution is pervasive in distal site metastatic colonization.

The evolution of metastasis, the spread of cancer to distal sites within the body, represents a lethal stage of cancer progression. Yet, the evolutionary dynamics that shape the emergence of metastatic disease remain unresolved. Here, using single-cell lineage tracing data in combination with phylogenetic statistical methods, we show that the evolutionary trajectory of metastatic disease is littered with bursts of rapid molecular change as new cellular subpopulations appear, a pattern known as punctuational evolution. Next, by measuring punctuational evolution across the metastatic cascade, we show that punctuational effects are concentrated within the formation of secondary tumours at distal metastatic sites, suggesting that qualitatively different modes of evolution may drive primary and metastatic tumour progression. Taken as a whole, our findings provide empirical evidence for distinct patterns of molecular evolution at early and late stages of metastatic disease and our approach provides a framework to study the evolution of metastasis at a more nuanced level than has been previously possible.

Therapeutic Potential of Bioactive Compounds from Millettia pinnata: Computational and In Vitro Approaches

Osteosarcoma is a very aggressive malignancy mostly of the long bones, including the arms and legs, and is most common in children and young adults. Defined by the uncontrolled proliferation of immature bone cells, this malignancy can lead to discomfort, edema, and the spread of cancer to distant sites. The objective of this work is to analyze the bioactive constituents of Millettia pinnata by computational and in vitro methods in order to uncover possible treatments for osteosarcoma. Molecular docking was used to identify bioactive compounds from M. pinnata leaf extract. These compounds were then subjected to in vitro investigations, which included testing for DPPH antioxidant activity, screening for phytochemicals, FTIR analysis, and GCMS analysis for chemical characterisation. Analysis of chemical interactions with osteosarcoma-associated proteins was conducted using Autodock, while the pharmacokinetics of the drugs were assessed using ADMET profiles. The computational analysis identified two bioactive compounds that have a strong propensity for binding to proteins associated with osteosarcoma, indicating their potential as therapeutic agents. In vitro assays confirmed antioxidant activity, while FTIR and GCMS analyses highlighted the extract’s diverse phytochemical composition. The findings underscore the promising potential of M. pinnata leaf extract in combating osteosarcoma, supported by molecular docking predictions. This study highlights the importance of integrating computational and biological techniques in drug discovery, demonstrating M. pinnata as a valuable source of novel therapeutic agents.

Metabolic Reprogramming and Adaption in Breast Cancer Progression and Metastasis.

Recent evidence has revealed that cancer is not solely driven by genetic abnormalities but also by significant metabolic dysregulation. Cancer cells exhibit altered metabolic demands and rewiring of cellular metabolism to sustain their malignant characteristics. Metabolic reprogramming has emerged as a hallmark of cancer, playing a complex role in breast cancer initiation, progression, and metastasis. The different molecular subtypes of breast cancer exhibit distinct metabolic genotypes and phenotypes, offering opportunities for subtype-specific therapeutic approaches. Cancer-associated metabolic phenotypes encompass dysregulated nutrient uptake, opportunistic nutrient acquisition strategies, altered utilization of glycolysis and TCA cycle intermediates, increased nitrogen demand, metabolite-driven gene regulation, and metabolic interactions with the microenvironment. The tumor microenvironment, consisting of stromal cells, immune cells, blood vessels, and extracellular matrix components, influences metabolic adaptations through modulating nutrient availability, oxygen levels, and signaling pathways. Metastasis, the process of cancer spread, involves intricate steps that present unique metabolic challenges at each stage. Successful metastasis requires cancer cells to navigate varying nutrient and oxygen availability, endure oxidative stress, and adapt their metabolic processes accordingly. The metabolic reprogramming observed in breast cancer is regulated by oncogenes, tumor suppressor genes, and signaling pathways that integrate cellular signaling with metabolic processes. Understanding the metabolic adaptations associated with metastasis holds promise for identifying therapeutic targets to disrupt the metastatic process and improve patient outcomes. This chapter explores the metabolic alterations linked to breast cancer metastasis and highlights the potential for targeted interventions in this context.

Numerical Bifurcations and Sensitivity Analysis of an SIVPC Cervical Cancer Model

We consider a mathematical model of cervical cancer based on the Natural History of Cervical Cancer. The model is a five dimensional system of the first order of ordinary differential equations that represents the interaction between the free Human Papilloma Virus (HPV) population and four cells sub-populations, i.e., the normal cells, infected cells by HPV, precancerous cells, and cancer cells. We focus our analysis to determine the existence conditions of the nontrivial equilibrium point, the bifurcations, and the sensitivity of the parameters that play important roles in metastasis. Based on the basic reproduction ratio of the system, we found that the infection rate, the new viruses production rate, the free viruses death rate, the infected cells growth rate, and the precancerous cells progression rate play important roles for the cancer spreads in the cellular level. By applying sensitivity and numerical bifurcation analysis, we found that there are some important bifurcations that trigger some irregular behaviours of the system, i.e., fold, Hopf, cusp and Bogdanov-Takens.

Next frontier in cancer treatment: an iPSC supported CAR-T cell therapies

The spread of cancer and huge number of cancer related deaths has made it imperative for scientist to search new diagnostic, prognostic and treatment tools for its effective management. Chimeric Antigen Receptor (CAR) T-cell (CAR-T) therapy has been brought into limelight as novel treatment strategy for cancer. In this review we briefly introduced the CAR-T therapy highlighting its successful application for various cancers along with the possibility of integrating the induced pluripotent stem cell (iPSC) technology with CAR-T technology to overcome its intrinsic limitation. The mechanism of CAR-T technology is based on the isolation of white blood cells through leukapheresis from patients’ blood or healthy donors followed by the isolation of T-cells (a type of immune cells). The isolated T-cells are engineered through using a viral vector or other methods to incorporate the CAR gene and expanded in the lab. This modification enables T cells to distinguish and attack antigens on the surfaces of cancer cells. However, this approach is not without its inherent limitations. CAR-T cell therapy notable limitation is the exhaustible availability of T cells within the donor or patient system, which can restrict the feasibility and effectiveness of therapeutic intervention. A potential solution to this limitation may lie in synergizing CAR-T technology with the induced pluripotent stem cell (iPSC) technology. The inherent potential of iPSC technology lies in its ability to provide an endless supply of T-cell resources. A substantial amount of research revealed the production of various human CAR-T cells using iPSC technology. Therefore, such combinatorial approach utilizing CAR-T technology for mounting an immunological attack against cancer with continues supply of T-cells through iPSCs technology can prove revolutionary in designing novel and pragmatic methods for cancer treatment.

A prospective observational study on iv compatibility, dose adjustment and ADR of chemotherapy drugs in oncology department at tertiary care hospital

Background: Cancer is the second leading cause of death worldwide. Chemotherapy is a standard modality of cancer treatment that uses chemical agents or drugs to destroy cancer cells in the cell cycles or use chemicals or drugs to inhibit cancerous cells growth and spread. The objective of this study was to assess the IV compatibility of chemotherapy drug in different solution, assess the frequency of ADR, classify ADR according to the class of drug and dose adjustment. Methods: In this study, cancer patients of either gender (aged 21-90) admitted on the oncology department of Bangalore Baptist Hospital were included in the study. Assessment of IV compatibility was done based on the prescription pattern, dose adjustment was done on the basis of body weight, BSA and hepatic and renal parameters. Adverse reactions reported by the patients, assessed by the doctors and nurses and changes in the laboratory parameters were analysed for the assessment of ADR. Results: A total of 43 patients met the inclusion criteria; among which 44% were male and 56% were female. The mean age of the study was 57.49. Breast cancer, stomach cancer and lung cancer were more prevalent. In the study 24 chemotherapy drugs were used among them 20 drugs were compatible in 0.9% normal saline and 4 drugs were compatible in 5% dextrose. Dose adjustment were done for 4 drugs which were Carboplatin, Paclitaxel, Trastuzumab and Ifosfamide. The average dose adjusted for Carboplatin, Paclitaxel, Trastuzumab and Ifosfamide were -0.46±3.3, 0.5±10.6, -10±0 and -50±0 respectively. Total of 25 adverse drug reaction were seen where vomiting, gastritis and anemia were more frequently seen. Alkylating agents showed more number of ADRs. Conclusions: From the study, it can be concluded that most of the chemotherapy drugs were compatible either in 5% dextrose or 0.9% normal saline. Dose adjustments were done on the basis of body weight and BSA. Alkylating agents showed ADR most frequently and least frequent was topoisomerase inhibitor. Vomiting was the most reported ADR.

Therapeutic Significance of NLRP3 Inflammasome in Cancer: Friend or Foe?

Besides various infectious and inflammatory complications, recent studies also indicated the significance of NLRP3 inflammasome in cancer progression and therapy. NLRP3-mediated immune response and pyroptosis could be helpful or harmful in the progression of cancer, and also depend on the nature of the tumor microenvironment. The activation of NLRP3 inflammasome could increase immune surveillance and the efficacy of immunotherapy. It can also lead to the removal of tumor cells by the recruitment of phagocytic macrophages, T-lymphocytes, and other immune cells to the tumor site. On the other hand, NLRP3 activation can also be harmful, as chronic inflammation driven by NLRP3 supports tumor progression by creating an environment that facilitates cancer cell proliferation, migration, invasion, and metastasis. The release of pro-inflammatory cytokines such as IL-1β and IL-18 can promote tumor growth and angiogenesis, while sustained inflammation may lead to immune suppression, hindering effective anti-tumor responses. In this review article, we discuss the role of NLRP3 inflammasome-mediated inflammatory response in the pathophysiology of various cancer types; understanding this role is essential for the development of innovative therapeutic strategies for cancer growth and spread.

Biogenesis and functional implications of extracellular vesicles in cancer metastasis.

Extracellular vesicles (EVs) play a crucial role in the complex process of cancer metastasis by facilitating cellular communication and influencing the microenvironment to promote the spread and establishment of cancer cells in distant locations. This paper explores the process of EV biogenesis, explaining their various sources that range from endosomal compartments to plasma membrane shedding. It also discusses the complex mechanisms that control the sorting of cargo within EVs, determining their chemical makeup. We investigate the several functions of EVs in promoting the spread of cancer to other parts of the body. These functions include influencing the immune system, creating environments that support the formation of metastases before they occur, and aiding in the transformation of cells from an epithelial to a mesenchymal state. Moreover, we explore the practical consequences of EV cargo, such as nucleic acids, proteins, and lipids, in influencing the spread of cancer cells, from the beginning of invasion to the creation of secondary tumor sites. Examining recent progress in the field of EV-based diagnostics and treatments, we explore the potential of EVs as highly promising biomarkers for predicting the course of cancer and as targets for therapeutic intervention. This review aims to provide a complete understanding of the biology of EVs in the context of cancer metastasis. By unravelling the nuances of EV biology, it seeks to pave the way for new tactics in cancer detection, treatment, and management.