MedComm – Oncology最新文献

The tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR), such as osimertinib and gefitinib, aumolertinib have been widely used in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. However, the discrepancy of pharmacokinetic features and distributions in important tissues between these EGFR-TKIs remains obscure. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with specificity and accuracy was established. After a single equivalent dose ratio or equal dose gavage, aumolertinib displayed the shortest elimination half-life time (t_1/2), while it showed the largest area under the concentration–time curve in mouse plasma and bone marrow among these 3 EGFR-TKIs. Furthermore, at the time of reaching maximum concentration (t_max) after single equivalent dose ratio gavage, the concentrations of aumolertinib were significantly higher than that of osimertinib and gefitinib in 9 important tissues of mice. Moreover, after single oral administration, aumolertinib displayed the highest concentration in plasma samples from EGFR mutation-positive NSCLC patients. Collectively, our findings manifest that the bioavailability and tissue distribution features of aumolertinib are superior to those of osimertinib and gefitinib, providing a pharmacokinetic basis for the clinical application of aumolertinib and the development of next-generation EGFR-TKIs.

Tumor metastasis is a multistep, inefficient process orchestrated by diverse signaling pathways. Compared to primary tumor cells, disseminated tumor cells inevitably encounter higher oxidative stress in foreign environments. The levels of reactive oxygen species (ROS) fluctuate dynamically during different metastatic stages, adding complexity to the regulation of metastatic progression. Numerous studies suggest that epigenetic remodeling, a key reversible mechanism of gene regulation, plays a critical role in responding to oxidative stress and controlling gene expression profiles that drive metastasis. Despite extensive research, a comprehensive understanding of how oxidative stress impacts metastasis through epigenetic modifications remains elusive, such as DNA methylation, histone modification, ncRNAs, and m⁶A modification. Epigenetic therapeutic strategies, such as DNMT inhibitors, HDAC inhibitors (HDACis), and miRNA mimics, have shown promise, yet challenges related to immunogenicity, specificity, and delivery also exist. Furthermore, due to limited understanding, some drugs targeting m⁶A modification have yet to be explored. In this review, we provided an overview of how oxidative stress influences tumor metastatic behavior, summarized the epigenetic mechanisms involved in these processes, and reviewed the latest advancements in epigenetic-targeted therapies, which may pave the way to develop novel strategy for preventing or treating tumor metastasis.

Gastric cancer (GC) ranks among the leading causes of cancer-related mortality globally. Often, its initial stages manifest subtly, and the infrequency of routine screenings contributes to late diagnoses in many cases. Systemic treatments for GC include chemotherapy, targeted therapy, and immunotherapy, among which immunotherapy is the first-line standard treatment for advanced GC. In recent years, immunotherapy has seen notable advancements, as evidenced by the Food and Drug Administration's approval of drugs such as nivolumab and pembrolizumab for GC treatment. Additionally, several other drugs are currently under rigorous preclinical and clinical investigation. This review aims to shed light on the recent advancements in immunotherapy for GC, particularly emphasizing the insights gained from phase 2/3 clinical trials that assess the efficacy, safety, and promise of various immunotherapeutic modalities, including immune checkpoint inhibitors, CAR-T-cell therapies, and cancer vaccines, in enhancing patient outcomes. Moreover, this review delves into the intricate immunological framework of GC, focusing on the tumor microenvironment, interactions among immune cells, and the roles of immune checkpoints such as PD-L1. We also address the hurdles and prospective paths forward in the realm of immunotherapy for GC, offering fresh viewpoints on potential therapeutic approaches in this evolving domain.

Despite significant advancements in the treatment of cancer, therapeutic resistance remains a major hurdle for the achievement of full cures. Besides being typically driven by intratumoral heterogeneity, such acquired resistance also relies heavily on cell-cell communication whereby extracellular vesicles (EVs) carrying resistance-related components can be transferred from drug-resistant cells or nontumorigenic members within tumor microenvironment (TME) to their sensitive neighbors. The cargo and membrane surface proteins of EVs derived from drug-resistant cells and TME cells carry abundant biological information, transferring therapy-resistant capacity to sensitive cancer cells. Hence, a deep understanding of the roles of EVs in cancer therapy resistance will facilitate identifying biomarkers and developing new approaches to restore therapy sensitivity. In this review, we summarize our current understanding regarding the causes and effects of EV-mediated cell–cell communication in drug resistance, with a particular notice on how various kinds of cargoes derived from different cells within TME are linked to the resistant phenotype. We also discuss how this knowledge can contribute to improvements in clinical practice, that is, the opportunities and challenges of EVs in functioning as potential biomarkers in predicting therapeutic resistance and, by extension, EV-based therapy in achieving deeper and longer-lasting clinical responses.

MicroRNAs (miRNAs) are key molecules that regulate gene expression. miRNAs regulate protein synthesis by binding to mRNA, influencing processes such as cell proliferation, metastasis, and apoptosis. They play a pivotal role in cancer development. Current research mainly explores miRNA mechanisms and applications, and the techniques underpinning this research are foundational to both basic science and clinical translation. However, no review has comprehensively examined miRNA mechanisms and applications from a technical perspective, creating a need for this work. Advances in RNA sequencing technology, CRISPR/Cas9 technology, and bioinformatics tools have deepened our understanding of miRNA interactions. miRNA can serve as a biomarker for cancer diagnosis and prognosis, with significant clinical potential. The development of miRNA mimics and inhibitors has brought new hope for cancer treatment, especially in reversing cancer drug resistance. This article reviews the vital role of miRNA interactions in cancer occurrence, development, diagnosis, and treatment, providing new perspectives and strategies for personalized medicine and cancer therapy.

Gastrointestinal (GI) tumors have always been a major type of malignant tumor and a leading cause of tumor-related deaths worldwide. The main principles of modern medicine for GI tumors are early prevention, early diagnosis, and early treatment, with early diagnosis being the most effective measure. Endoscopy, due to its ability to visualize lesions, has been one of the primary modalities for screening, diagnosing, and treating GI tumors. However, a qualified endoscopist often requires long training and extensive experience, which to some extent limits the wider use of endoscopy. With advances in data science, artificial intelligence (AI) has brought a new development direction for the endoscopy of GI tumors. AI can quickly process large quantities of data and images and improve diagnostic accuracy with some training, greatly reducing the workload of endoscopists and assisting them in early diagnosis. Therefore, this review focuses on the combined application of endoscopy and AI in GI tumors in recent years, describing the latest research progress on the main types of tumors and their performance in clinical trials, the application of multimodal AI in endoscopy, the development of endoscopy, and the potential applications of AI within it, with the aim of providing a reference for subsequent research.

Not all patients can benefit from chemotherapy due to the various of tumor type, stage, location, and the different distribution of immune cells in tumor immune microenvironment (TIME). Immune cells are widely involved in every step of cancer progression, including immune escape, metastasis, drug response, and prognosis. In this study, we explored the transcriptome data of 10 solid tumors treated with chemotherapy to identify the role of immune cells. We downloaded the transcriptome and mutation data of 10 cancers from TCGA databases, and used ESTIMATE and CIBERSORT algorithms to assess the proportion of immune cells in the TIME. According to the proportion of specific immune cell infiltration (SICI) of CD8⁺ T cells and M1 macrophages to group the patients, we found that compared with the SICI low and medium groups, the SICI high group had a larger tumor mutation burden, more gene mutations with targeted drugs, more activation of immune checkpoints (PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT), and immune molecules (CD8a, CD80, CD86, TLR2, HLA-A, HLA-B, and CD11a) (p < 0.05). Therefore, we can select an appropriate treatment for patients by clarifying the proportion of immune infiltration of CD8⁺ T cells and M1 macrophages in the TIME.