Current Cancer Drug Targets - Online First

With advancements in technology, single-cell RNA sequencing has emerged as a powerful 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 pathways 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 understanding helps in identifying potential drug targets. Additionally, it aids in predicting therapeutic responses. This high-resolution gene expression analysis provides a new perspective and opportunity 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 processes 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 challenges 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 development, and support the translation of clinical research into practice, ultimately enabling physicians to design more precise and personalized treatment strategies.

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 multi-step 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.

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.

Glioblastoma multiforme (GBM) is a complex and aggressive brain tumor that presents significant diagnostic and therapeutic challenges in both adults and children. Understanding the pathogenesis, molecular biology, symptom presentation, and imaging features of GBM is vital for effective therapy. This review summarizes current knowledge on pediatric GBM, specifically Pediatric Diffuse High-Grade Gliomas (pHGG), focusing on diagnosis and treatment. GBM typically arises from the cerebral hemispheres, with gross features marked by heterogeneous morphology and aggressive cell populations. Recent advances in genomic research have shed light on distinct molecular pathways associated with primary and secondary GBMs. Clinical symptoms vary widely but commonly include neurological deficits and increased intracranial pressure. Magnetic resonance imaging (MRI), with its excellent soft tissue contrast, is crucial for diagnosing and monitoring GBM. Emerging techniques, such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI), provide insights into the tumor's microstructure and vascularity, assisting in the development of therapeutic strategies and response assessment. Despite advances in imaging, challenges remain in accurately diagnosing and managing pediatric GBM due to its molecular heterogeneity and unique biological behavior. New therapeutic approaches, including targeted therapies and immunotherapy, offer hope for improving outcomes in children with GBM. Clinical trials are ongoing to evaluate these treatments alongside standard options, such as surgery, radiotherapy, and chemotherapy, to meet the unmet needs of pediatric oncology. A multidisciplinary approach, tailored to the individual characteristics of both the patient and the tumor, is essential to optimize treatment and outcomes for pediatric GBM patients. This review highlights the role of advanced MRI techniques in diagnosis, treatment, and monitoring while emphasizing the need for further research and clinical trials to develop more effective therapies for this devastating disease. Recent studies indicate a median survival rate of 12-18 months for pediatric GBM, with treatment response varying based on molecular subtypes. Clinical trials show that IDH-wild-type tumors exhibit poorer prognosis, whereas targeted therapies are improving outcomes in select patient groups.

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 regulatory 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 expression 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 personalized treatment strategies in breast cancer.

Breast cancer (BC) remains a leading cause of cancer-related mortality among women worldwide, underscoring the urgent need for sensitive, non-invasive biomarkers to improve diagnosis, prognosis, and treatment monitoring. Traditional biomarkers like ER, PR, and HER2 offer limited efficacy, particularly for heterogeneous subtypes such as triple-negative breast cancer (TNBC). Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as promising biomarker carriers due to their stability and ability to encapsulate diverse bioactive molecules reflective of the parental cell’s state. Among EV cargoes, tRNA-derived fragments (tRFs), which are small non-coding RNAs produced by precise cleavage of tRNAs, have gained increasing attention. Once considered mere degradation products, tRFs are now recognized for their roles in gene regulation, translation control, apoptosis modulation, and immune response. Recent studies have revealed the selective enrichment of tRFs within EVs, highlighting their role in intercellular communication in breast cancer. Differential expression of EV-associated tRFs correlates with BC subtype, stage, and patient prognosis, highlighting their potential as minimally invasive biomarkers. Specifically, altered levels of certain 5′- and 3′-tRFs in patient sera and tumor tissues have been associated with poor survival, metastasis, and therapeutic resistance. Despite these promising findings, gaps remain regarding the mechanisms of tRF sorting into EVs and their functional impact on the tumor microenvironment. This review systematically examines the current understanding of EV-associated tRFs in breast cancer, emphasizing their clinical relevance, detection strategies, and translational potential. By addressing existing challenges, we aim to provide insights into the utility of EV-tRFs as novel biomarkers and therapeutic targets in BC.