Current cancer drug targets最新文献

Head and Neck Cancer (HNC) encompasses a diverse group of malignancies arising in the oral cavity, pharynx, larynx, and related structures. It represents a significant global health bur- den due to its high incidence, aggressive progression, and strong associations with environmental and viral risk factors like tobacco use and HPV infection. HNC, particularly squamous cell carcinoma, ranks as the seventh most common cancer worldwide. Despite the established role of these risk factors, the molecular mechanisms driving disease progression remain underexplored, especially in the context of specific biomarkers like Nucleolin (NCL). Nucleolin, a multifunctional protein, is pivotal in cancer progression, regulating cell proliferation, angiogenesis, and apoptosis. Data from The Cancer Genome Atlas (TCGA) reveal significant overexpression of NCL in HNC, particularly in advanced stages, correlating with poor prognosis and reduced patient survival. These findings highlight its potential as a diagnostic and therapeutic target. This review provides a fresh perspective on the underexplored potential of NCL as a therapeutic target in HPV-induced HNC and oral cancer. Emerging approaches, such as the AS1411 aptamer and F3 peptide, offer promising avenues for targeting NCL, paving the way for more effective, personalized cancer therapies.

Gastric cancer is closely associated with the aging process, with its incidence and mortality rates significantly increasing with age, peaking around 85 years. Despite advance-ments in treatment modalities, current diagnostic and therapeutic approaches remain insuffi-cient, resulting in persistently low five-year survival rates among patients. The expanding global population and the intensifying aging process are anticipated to exacerbate the global burden of gastric cancer further, underscoring the urgency of exploring novel therapeutic strat-egies. A complex relationship exists between gastric cancer and cellular senescence, although the precise mechanisms remain incompletely understood. Cellular senescence is prevalent in gastric cancer treatment, typically serving as a natural anti-tumor barrier by inhibiting the un-controlled proliferation and malignant transformation of cancer cells. However, prolonged cel-lular senescence may trigger the secretion of pro-inflammatory factors, thereby promoting tu-morigenesis and progression. A systematic analysis of existing research data has revealed sig-nificant intersections between therapeutic targets for gastric cancer and senescence-associated signaling pathways, suggesting that modulating these critical nodes may constitute a pivotal mechanism for exploring novel therapeutic strategies bridging gastric cancer treatment and se-nescence. Circular RNAs (circRNAs) have garnered considerable attention with the advance-ment of bioinformatics and high-throughput sequencing technologies. As key regulatory fac-tors, circRNAs can modulate microRNAs (miRNAs) through a "sponge adsorption" mecha-nism, thereby influencing the post-transcriptional modification of critical genes. Given their high structural stability and widespread distribution in vivo, circRNAs have emerged as ideal candidate molecules for biomarkers and therapeutic targets in gastric cancer. This review fo-cuses on the mechanisms by which circRNAs, through sponging miRNAs, regulate key nodes in therapeutic targets and senescence signaling pathways in gastric cancer.

Cancer is a major health problem and the second leading cause of death worldwide. Chemotherapy remains the mainstay therapeutic option to treat cancer patients, which consists of conventional, hormonal, and/or targeted therapies. However, the significant adverse effects, negative impact on patients' quality of life, and high costs of some medications, as well as the challenges associated with developing new drugs, are prompting the scientific community to seek innovative and alternative treatment strategies. One such strategy is drug repurposing, the use of existing drugs, already approved for other medical conditions for cancer treatment, lev-eraging their known safety and toxicity profiles. Among these groups are the selective seroto-nin reuptake inhibitors (SSRIs) that target serotonin transporter (SERT). In this review, we presented the mechanism of action of SSRIs on the systems biology level, along with their network pharmacology related to protein-protein interactions. We also showed the association of SSRIs and SERT with various diseases, including several types of cancer. Knowing the expression of SERT in cancer and being a target for SSRIs, studies have been investigating the repurposing of SSRIs for cancer treatment. This review also presents a summary of several clinical and preclinical studies that have investigated the use of SSRIs either as single agents or in combination with conventional chemotherapy for cancer treatment, showing promising results. Collectively, they have shown the antiproliferative and growth inhibition effects on cancer cells and/or tumors. We also presented the mechanism(s) of action and pathways these drugs are acting in cancer, along with molecular changes in cellular proteins and enzymes.

Background: The thiazole nucleus serves as a bioactive synthetic scaffold in drug design and discovery due to its diverse pharmacological activities. It was discovered that many types of thiazole derivatives, including those with one, two, or three substitutions, five- or six-membered heterocycles, fused rings, and thiazole-derived Schiff bases, hydrazinyl derivatives, amides, chalcones, and bis-thiazoles, can fight cancer. Thus, the structural diversity of thiazole nuclei makes it one of the significant areas of research in the pharmaceutical field.

Objective: We would like to elaborate on the recent literature available on the antiproliferative property of molecules bearing 1,3-thiazole nuclei.

Methods: This review summarises the anticancer potency of thiazole derivatives collected from recently available scientific literature. We extracted the information from online databases like PubMed, Scopus, and Web of Science using relevant keywords from 2016 to the present. We discuss the current state of thiazole derivatives and highlight the most promising compounds. We also describe how they work and what their half-maximum inhibitory concentration (IC50) is.

Results: Based on our extensive literature review, we found that thiazole derivatives exhibit anticancer activity through their ability to induce apoptosis in cancer cells, mitochondrial membrane disruption by blocking signalling pathways such as Akt, NFkB, PI3K, and Src/Abl, and inhibition of proteins responsible for cell growth. Moreover, thiazole-protein interactions essential for cancer inhibition are predominantly regulated by hydrogen bonding, supported by the sulphur and nitrogen atoms in the thiazole molecule, which effectively interacts with the amino acids serine, tyrosine, and glutamine. π-π stacking and π-cation interactions involving aromatic amino acids such as tryptophan, tyrosine, and phenylalanine, along with hydrophobic effects and van der Waals forces, play a crucial role in thiazole-protein interactions. These interactions dictate binding affinity and efficacy, measured through thermodynamic characteristics such as Binding Constant (Kb), Dissociation Constant (Kd), and Gibbs free energy (ΔG). Comprehending these features is essential for the development of effective thiazole-based anticancer pharmaceuticals.

Conclusion: This cumulative information is enough to give new ideas for the rational drug design of thiazole-based derivatives and could be pursued as a promising lead in the future for the management of cancer threats.

The initiation and progression of breast cancer generally involve complex immune regulatory mechanisms, with increased expression of programmed cell death ligand 1 (PD-L1) as an essential factor for immune evasion and the formation of a tumor-promoting immune microenvironment. Emerging evidence underscores the regulatory role of non-coding RNAs (ncRNAs) in modulating PD-L1 expression, influencing immune evasion, tumorigenesis, and therapy resistance in breast cancer. Therefore, it is crucial further to clarify alternative regula-tory mechanisms that control PD-L1 expression. The variations in PD-L1 expression among different breast cancer subtypes and the mechanisms by which ncRNAs regulate the expres-sion of PD-L1 are delineated. This study explores the potential and challenges of combining ncRNA-based therapy with PD-L1 inhibitors, offering insights into PD-L1 regulation and per-sonalized treatment strategies in breast cancer.

Introduction: Lung adenocarcinoma (LUAD) remains a lethal disease worldwidewith a poor prognosis. The ecotropic viral integration site 5 (EVI5) is a crucial oncogene andmediator of cell division processes, and it extensively participates in tumorigenesis and progression. However, the role of EVI5 in LUAD progression remains elusive. This study aimedto further explore the underlying mechanisms of EVI5's involvement in LUAD development.

Methods: The GEO database was employed to investigate the expression of EVI5 in LUAD and normal tissues, while the Kaplan-Meier Plotter database was utilized to assess its correlation with patient prognosis. Stable cell lines with EVI5 knockout and overexpression were constructed, and Western blotting was performed to detect EVI5 protein expression levels to validate the successful establishment of the stable cell lines. The abilities of proliferation, invasion, and migration of LUAD cells after transfection were analyzed using CCK-8, colony formation, transwell, and wound healing assays. Western blotting, immunofluorescence, and qRT-PCR were further carried out to measure the protein and mRNA expression levels associated with the ERK1/2-c-Myc signaling pathway. Finally, functional rescue experiments were performed on LUAD cells to further explore and verify the signaling pathway.

Results: EVI5 was found to be highly expressed in lung adenocarcinoma tissues and correlated with poor prognosis. EVI5 overexpression promoted the malignant behavior of lung adenocarcinoma, whereas its knockout produced the opposite effect. Mechanistically, ERK1/2-cMyc, the key signaling pathway in the malignant progression of LUAD, was further validated by an ERK1/2 pathway inhibitor.

Conclusion: Our study demonstrated for the first time that EVI5 promotes malignant progression through the activation of the ERK1/2-c-Myc signaling axis, providing new insights into the pathogenesis of LUAD.

Lung cancer is an aggressive malignancy and one of the leading causes of cancer-related mortality worldwide. Compared with traditional treatments, the development of pre-cision treatment programs, such as targeted therapy and immunotherapy, has progressively transformed non-small cell lung cancer (NSCLC) with driver mutations, becoming a clini-cally controllable chronic disease. Among the treatments for lung cancer, monospecific anti-bodies gradually show effectiveness but also expose their susceptibility to drug resistance, off-target effects, and other limitations. Therefore, bispecific antibodies have been developed, which have two different antigen-binding sites so that they can bind two distinct antigens or two distinct epitopes of the same antigen with adjustable specificity and do not easily produce drug resistance. This article reviews the design strategies and mechanism of bispecific anti-bodies, summarizes the latest progress in clinical trials involving bispecific antibodies for lung cancer, and analyzes the current challenges and future directions in this area of research.

Background: Hypoxia plays a crucial role in malignant tumor formation, primarily mediated by hypoxia-inducible factors (HIFs). Despite extensive research, the complexities and prognostic implications of the EGLN gene family (EGLN1, EGLN2, EGLN3) in cancers remain unclear.

Methods: Utilizing public databases (TCGA, GTEx, TARGET, GEO) and bioinformatics tools, a comprehensive analysis of EGLN genes across various cancer types was conducted. Gene ex-pression, mutation data, stemness scores, and clinical information were integrated to evaluate the mutation landscape, expression levels, and prognostic values of EGLNs. Enrichment and pathway analyses explored EGLN-associated biological processes and functional networks. ssGSEA con-structed EGLN scores for prognostic evaluation. Colocalization analysis combined eQTL and GWAS data to investigate genetic variations in cervical cancer. Immunohistochemistry validated EGLN expression in cervical cancer tissues.

Results: EGLN genes showed differential expression across cancer types. EGLN1 overexpres-sion was associated with worse survival in cervical squamous cell carcinoma (CESC), pancreatic adenocarcinoma (PAAD), and neuroblastoma (NB), while EGLN3 was linked to poor survival in CESC, lung adenocarcinoma (LUAD), and kidney cancers. EGLNs also demonstrated varied roles in modulating tumor immune activity and heterogeneity.

Conclusion: This study provides new insights into EGLN biology and identifies EGLN1 as a potential biomarker for cervical cancer.