Current cancer drug targets最新文献

With advancements in technology, single-cell RNA sequencing has emerged as a power-ful tool in cancer drug discovery. This technique enables the construction of gene expression profiles at the individual cell level, offering detailed insights into cellular heterogeneity and molecular path-ways involved in tumor development. It enables researchers to gain a deeper understanding of tumor heterogeneity. Researchers can study cell subpopulations and gene expression patterns. This under-standing helps in identifying potential drug targets. Additionally, it aids in predicting therapeutic responses. This high-resolution gene expression analysis provides a new perspective and oppor-tunity for cancer drug development, which is expected to accelerate the discovery and development process of new anti-cancer drugs. This article provides a comprehensive overview of the basic pro-cesses and developmental trajectory of single-cell RNA sequencing technology, with a particular emphasis on its applications in various aspects of cancer drug discovery. It also addresses the chal-lenges faced by single-cell RNA sequencing and potential future directions. This review aims to enhance readers' understanding of single-cell sequencing, inspire new ideas for oncology drug de-velopment, and support the translation of clinical research into practice, ultimately enabling physi-cians to design more precise and personalized treatment strategies.

Background: Gastrointestinal (GI) cancer, a multifactorial disease, encompasses a group of malignancies that affect the gastrointestinal system. Being the second leading con-tributor to cancer-related deaths, GI cancer has become the burning issue of human health. Despite advances in treatment, the diverse nature of GI cancer indicates that a one-size-fits-all solution is not applicable.

Introduction: The gut microbiome can be therapeutically modulated by utilizing prebiotics, postbiotics, and synbiotics. Fermentation of prebiotics produces postbiotic compounds. To-gether the prebiotics and probiotics combination can be used as synbiotics which will be more beneficial.

Methods: PubMed and Google scholar search engine tools have been utilized to access ref-erences about the idea of this review to demonstrate the therapeutic modulation of microbiota, residing in the gut, which utilizes postbiotics, prebiotics and synbiotics for combating GI cancer.

Results: Exploration of prebiotics, postbiotics, and synbiotic compounds has given us de-tailed information about their contribution to combating GI cancer.

Conclusion: Intake of a combination of prebiotic, postbiotics and synbiotics can inhibit the growth of cancer cells, and activate protective and stress-resistant mechanisms in healthy cellswhich couldbe more beneficial than the administration of prebiotics or postbiotics or synbiotics alone in diminishing the risk of GI cancer.

Objective: SPON2 is an extracellular matrix constituent belonging to the Mindin-F-spondin protein family. Our previous study proved that SPON2 emerges as a novel biomarker in renal fibrogenesis. However, the role of SPON2 in regulation and its impact on RCC progression remains uncertain.

Methods: The TCGA and GEO databases were used to explore the expression of SPON2 in RCC. Western blot was used to detect the expression of SPON2 between RCC and normal samples. Survival analysis and gene set variation analysis were performed to discover the prognostic significance and underlying mechanism of SPON2 in RCC. The role of SPON2 was detected by CCK8, wound healing, invasion, and xenograft model assays. Autophagy-related experiments verified the bioinformatic findings.

Results: Bioinformatic analysis revealed significantly higher SPON2 expression in RCC, which was found to be associated with improved overall survival in patients with high SPON2 levels. Detection of clinical samples revealed an increase in SPON2 expression within the context of ccRCC tissues. In addition, data from in vitro assays revealed that SPON2 overexpression significantly enhanced the proliferative and migratory capacity of cell lines. Xeno-graft experiments demonstrated the accelerated tumor growth effect of SPON2. Mechanistic investigation showed that the PI3K/AKT/mTOR pathway was inhibited by SPON2.

Conclusion: Our data illustrated that SPON2 functions as an oncogene in the tumorigenesis of RCC tumorigenesis, which is accompanied by an inverse relationship between SPON2 expression levels and patient prognosis. The underlying mechanism likely involves the promotion of autophagy by modulating the PI3K/AKT/mTOR pathway.

Protrusion and adhesion occur at the foremost point of cells during cell migration, while contraction and detachment occur at the rear of the cells. The combined action of cytoskeletal dynamics, vesicular trafficking, and signaling networks initiates this multistep process. The development of a novel exosome-like organelle called migrasomes, which may play roles in intercellular signaling, and which originate from retraction fibers at the back of migrating cells. Migrasomes are a particular kind of extracellular vesicle that is placed by a special mechanism and left behind by migrating cells. The proteins called integrins, which connect cells to the extracellular matrix (ECM), regulate the mobilization of migrasome. The function of migrasomes is to preserve cellular homeostasis and communication between cells. By observing this literature, we attempted to ascertain the potential role that migrasomes will play in the future in illnesses involving migrating cells, like immune system problems, tumor metastasis, and other disorders.

In recent years, immunotherapy has demonstrated significant clinical effectiveness. However, challenges such as low response rates, severe treatment-related side effects, and acquired immune tolerance persist in tumor immunotherapy. Metabolic dysregulation is acknowledged as a principal factor in tumor growth, with aerobic glycolysis, or the Warburg effect, being a defining characteristic of numerous cancers. The enhanced uptake of glucose and glycolysis provides the necessary intermediates for anabolic reactions, which are essential for the proliferation of cancer cells, while simultaneously supplying sufficient energy. How-ever, the concomitant increase in lactate production contributes to immunosuppression within the tumor microenvironment. Tumor cells exploit lactate anabolism, lactate shuttling, and ly-sine lactylation modifications, which significantly diminish the efficacy of immunotherapy. The treatment targeting lactate anabolism or lactate transport proteins may prove an effective strategy for enhancing the effectiveness of cancer immunotherapy. This review provides a comprehensive overview of the role of lactate in anti-tumor immunotherapy, with the objective of deepening the understanding of the importance of lactate monitoring in cancer treatment. By elucidating these mechanisms, we aim to suggest innovative avenues for clinical cancer management, potentially improving therapeutic outcomes and overcoming the existing limita-tions of immunotherapy.

Introduction: RC48 is an anti-HER2 antibody‒drug conjugate that demonstrates antitumor activity in colon cancer with both high and low HER2 expression. Our study aimed to investigate the underlying mechanisms of RC48 on colon cancer cells with varying levels of HER2 expression.

Methods: The effects of RC48 on HER2 high-expressing HT29 colon cancer cells and low-expressing SW480 cells were assessed using transwell assays and flow cytometry. Proteomic analysis was carried out to explore the mechanisms by which RC48 inhibits the growth of HT29 and SW480 cells. β-Galactosidase staining and ELISAs were performed to validate the promotion of senescence in colon cancer cells by RC48. Bioinformatics analysis revealed the correlation between differentially expressed proteins and HER2 expression.

Results: RC48 inhibited the growth of HT29 and SW480 cells. Proteomic analysis revealed that RC48 enhanced CDKN1A expression in HT29 and SW480 cells. KEGG analysis indicated that CDKN1A expression was associated with the cellular senescence signaling pathway. RC48 upregulated CDKN1A expression in HT29 and SW480 cells, whereas the expression of other proteins related to the cellular senescence pathway was reduced. CDKN1A gene overexpression suppressed HT29 and SW480 cells. β-Gal staining demonstrated that RC48 promoted senescence in colon cancer cells, and RC48 enhanced senescence-associated secretory phenotype factor secretion in ELISAs. The close correlation between CDKN1A and HER2 expression was derived from the database.

Discussion: This study provides important insights into the antitumor mechanism of RC48, suggesting for the first time that CDKN1A-mediated cellular senescence may be a key mechanism underlying its therapeutic effect in HER2-high and low-expressing colon cancer, thereby offering a new theoretical basis for optimizing its clinical application. However, in vivo and clinical validation are lacking, and the functional role of CDKN1A, as well as its regulatory relationship with HER2, requires further investigation.

Conclusion: RC48 exerts antitumor effects on both HER2-high- and HER2-low-expressing colon cancer cells. RC48 may induce senescence in both high- and low-HER2 expressing co-lon cancer cells by increasing CDKN1A protein expression. Moreover, there is a close correlation between CDKN1A and HER2 expression.

Background: Colorectal cancer (CRC) is among the most widespread malignancies worldwide and is a leading cause for cancer mortality. The interstitial interaction between cancer and stem cells is important during cancer cell metastasis.

Objective: In this study, we aimed to elucidate the regulatory role and the underlying mechanisms controlling the activity of exosomes derived from cancer stem cells (CSCs).

Methods: Our group isolated exosomes from CSCs and non-CSCs to examine their regulatory mechanisms using Transwell migration, Cell Counting Kit-8 (CCK-8), and 5-ethynyl-2'-deoxyuridine (EdU) assays.

Results: The role of Eukaryotic Translation Initiation Factor 3 Subunit B (EIF3B) in CRC was examined using an in vivo tumorigenesis mouse model. It was found that treatment with exosomes isolated from CD133⁺ cells (CD133+Exos) promoted the proliferation and migration of SW480 cells. The downregulation of EIF3B reduced the proliferation and migration-promoting effects of CD133⁺ Exos on SW480 cells. Furthermore, CD133⁺ Exos treatment promoted the tumorigenesis of SW480 cells.

Conclusion: Our findings demonstrate that CSC-derived exosomes transport EIF3B into CRC cells to initiate epithelial-to-mesenchymal transition (EMT) and promote metastasis.

Cancer poses a major health burden worldwide, necessitating the development of novel therapeutic approaches. Personalized cancer vaccines represent a promising form of immunotherapy that enhances the ability of the immune system to recognize and destroy tumor cells through tumor-associated and cancer-specific antigens. This review categorizes cancer vaccines into preventive, therapeutic, and personalized vaccines, discussing their mechanisms, clinical applications, and current FDA-approved examples, such as Sip-uleucel-T and HPV vaccines. We highlight the recent advances in RNA-based vaccines, viral vectors, and nanotechnology, along with the synergistic role of cancer vaccines and immune checkpoint inhibitors in improving therapeutic efficacy. Overcoming ethical, regulatory, and technological barriers through global collaboration is essential for maximizing vaccine efficacy and enhancing patient outcomes. This review highlights the pivotal role of personalized vaccines in advancing precision medicine and reshaping cancer treatment paradigms.

Introduction: Euphorbia humifusa Willd (EH) is a traditional medicinal herb in China. However, the anti-prostate cancer active compounds of EH and their molecular mechanisms have yet to be elucidated.

Methods: The peaks of EH water extract in the fingerprinting were analysed using liquid chromatography coupled to quadrupole time of flight mass spectrometry. The cell viability of 22RV1 cells was determined via MTT. The active compounds and potential targets were screened in silico. The prostate cancer-associated targets were collected from the GeneCards database. The herb-compound-target-disease (H-C-T-D) and PPI networks were constructed to predict key targets. The molecular docking analysis of the active compounds with key targets was conducted using Autodock Vina 1.1.2. Western blot analysis was performed to evaluate the protein expression.

Results: LC-MS results demonstrated that EH water extract is a rich source of phenolics and flavonoids. EH water extract inhibited the viability of 22RV1 cells in a time-and dosedependent manner. Moreover, the in silico screening results identified 17 active compounds from EH with 518 prostate cancer-related key genes. Moreover, an H-C-T-D network analysis combined with the PPI network results effectively identified seven chemical compounds, oestrogen receptor 1, and androgen receptor (AR) to be highly related to prostate cancer. Furthermore, molecular docking results showed that 4',5-dihydroxyflavone, ensaculin, luteolin, hypolaetin, quercetin, and kaempferol had a strong binding affinity with AR. Finally, Western blot results demonstrated that EH water extract, quercetin, kaempferol, and luteolin significantly down-regulated the AR protein expression in 22RV1 cells.

Conclusion: These results suggest that EH may provide a new promising therapeutic for prostate cancer treatment.

Background: Numerous studies have suggested a close association between cancer stem cells (CSCs) and the tumor microenvironment (TME), suggesting that cancer stem-ness might also contribute to ICI resistance. However, the interplay between these physio-logical processes in urothelial bladder cancer (UBC) remains unclear.

Method: A meta-analysis was performed using the UBC Single-cell RNA sequencing (scRNA-seq) dataset, and tumor stemness gene sets (Ste.genes) were obtained. The relationship between Ste.genes and ICI response, as well as response to drug therapy, was investigated using Tumour Immune Dysfunction and Exclusion (TIDE) and drug sensitivity analyses. Machine learning based on Ste.genes was also used to predict ICI response.

Results: A hypoxia-related tumor subgroup associated with angiogenesis and tumor metastasis was identified, and prognostic models were constructed based on hypoxic tumor subgroups. It was also found that the Ste.genes score was associated with cellular immunity, tumor immunotherapy response, and drug sensitivity. Multiple machine learning models were used to predict ICI response based on Ste.genes, and the AUC was greater than 0.7, indicating that Ste.genes can predict ICI response effectively.

Conclusions: In this study, the analysis of UBC scRNA-seq data provided further insight into the role of hypoxic tumor subpopulations in tumor development in UBC, and a prognostic model was constructed. Additionally, an association was found between cell stemness and resistance to immunotherapy as well as drug sensitivity in UBC. Ste.genes were extracted and utilized to predict the ICI response.