Medical Oncology最新文献

Pancreatic ductal adenocarcinoma (PDAC) has proven to be a formidable cancer primarily due to its tumor microenvironment (TME). This highly desmoplastic, hypoxic, and pro-inflammatory environment has not only been shown to facilitate the growth and metastasis of PDAC but has also displayed powerful immunosuppressive capabilities. A critical cell involved in the development of the PDAC TME is the fibroblast, specifically the antigen-presenting cancer-associated fibroblast (apCAF). The pro-inflammatory environment of PDAC induces the proliferation of apCAFs, promoting immunosuppression through immune cell inactivation, immune response regulation, and expression of CD74. In conjunction with apCAFs and tumor cells, CD74 serves as a versatile promoter of PDAC by preventing tumor antigen-expression on tumor cells, upregulating the expression of immunosuppressive chemical mediators, and activating proliferative pathways to induce PDAC malignancy. This review will highlight critical mediators and pathways that promote the PDAC stroma and TME with its hypoxic and immunosuppressive properties. Further, we will highlight the nature of apCAFs and CD74, their specific roles in the PDAC TME, and their potential as targets for immunotherapy.

N6-methyladenosine (m6A) plays a pivotal role in regulating epitranscriptomic mechanisms and is closely linked to the normal functioning of diverse classes of RNAs, both coding as well as noncoding. Recent research highlights the role of m6A RNA methylation in the onset and progression of several cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCC ranks as the seventh most common cancer globally, with a five-year patient survival rate of just 50%. Elevated m6A RNA methylation levels and deregulated expression of various m6A modifiers, i.e. writers, readers, and erasers, have been reported across nearly all HNSCC subtypes. Numerous studies have demonstrated that m6A modifications significantly impact key hallmarks of HNSCC, such as proliferation, apoptosis, migration, and invasion. Furthermore, m6A impacts epithelial-mesenchymal transition (EMT), drug resistance, and aerobic glycolysis, and disrupts the tumor microenvironment. Additionally, transcripts regulated by m6A in HNSCC present themselves as potential diagnostic and prognostic biomarkers. This review attempts to comprehensively summarize the role of m6A RNA methylation and its modifiers in regulating various facets of HNSCC pathogenesis.

Acute Lymphoblastic Leukemia (ALL) is a heterogeneous blood cancer characterized by the uncontrolled growth of immature lymphoid cells due to dysregulated signaling pathways. It is the most common pediatric cancer, with high cure rates in children, but significantly lower survival rates in adults. Current theranostic strategies, including chemotherapy, immunotherapy, and nanomedicine, aim to improve detection and treatment precision but are limited by side effects, drug resistance, high costs, and stability issues. Notably, extracellular vesicles (EVs) offer a promising alternative, addressing these limitations through their natural biocompatibility and targeted delivery capabilities. EVs play a dual role in ALL: they contribute to leukemia progression by promoting tumor growth, immune suppression, and drug resistance via the transfer of oncogenic molecules, while also serving as valuable non-invasive biomarkers due to their specific miRNA and protein content. Their ability to deliver therapeutic agents directly to leukemic cells, combined with their stability and low immunogenicity, makes EVs a compelling tool for improving ALL treatments. Indeed, by targeting the molecular pathways influenced by EVs or leveraging them for drug delivery, innovative therapeutic strategies can be developed to enhance treatment outcomes and reduce side effects. Thus, EVs represent a promising frontier for advancing theranostic strategies in ALL, offering new opportunities to improve diagnosis and treatment while overcoming the limitations of traditional therapies. This review will explore the dual roles of EVs in ALL, addressing their contributions to disease progression and their potential as therapeutic agents and biomarkers for early diagnosis and targeted therapies.

This letter addresses the recent study by Zhou et al. on NDUFA4L2's role in colon adenocarcinoma (COAD), highlighting its potential as a therapeutic target. While the research is laudable, we identify areas for further refinement. Firstly, we suggest employing Weighted Gene Co-expression Network Analysis (WGCNA) to better understand NDUFA4L2's functional role in COAD by examining gene modules that co-vary with its expression. Secondly, we recommend expanding the analysis to include potential drugs targeting NDUFA4L2 using the Comparative Toxicogenomics Database (CTD) and molecular simulations to validate these interactions. Lastly, we propose Mendelian randomization analysis to establish a causal link between NDUFA4L2 expression and COAD risk. By implementing these suggestions, the study could be significantly enhanced, offering deeper insights into COAD's molecular mechanisms and more precise therapeutic strategies. Our commentary aims to enrich the genomic findings and contribute to the advancement of COAD research.

The 5-fluorouracil (5-FU)-based chemotherapy regimen is a primary strategy for treating pancreatic cancer (PC). However, challenges related to 5-FU resistance persist. Investigating the mechanisms of 5-FU resistance and identifying a clinically viable therapeutic strategy are crucial for improving the prognosis of PC. Here, through clinical samples analysis, we found that the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in mevalonate metabolism, is negatively correlated with the efficacy of 5-FU treatment. There is a significant correlation between HMGCR and the pyroptosis marker gasdermin D (GSDMD), and the HMGCR inhibitor simvastatin can significantly inhibit the activation of pyroptosis signaling. The exogenous addition of geranylgeranyl pyrophosphate (GGPP), a key metabolite of the mevalonate pathway, can significantly reduce sensitivity to 5-FU, and simvastatin combined with 5-FU demonstrates a strong synergistic effect. Furthermore, in organoid models and genetically engineered mice with spontaneous PC, the combination of simvastatin and 5-FU significantly inhibits tumor growth. In conclusion, our study reveals the critical role of the mevalonate pathway in 5-FU resistance and proposes a clinically feasible combination therapy strategy.

Thapsigargin, a sesquiterpene lactone derived from Thapsia garganica L., has demonstrated mixed potential as an anticancer agent due to its potent ability to disrupt calcium signaling and induce apoptosis. This review evaluates the chemopreventive and chemotherapeutic potential of thapsigargin, focusing on its molecular mechanisms and toxicity. An extensive literature review of studies published since 2015 was conducted using databases such as PubMed/MedLine and Science Direct. Findings indicate that thapsigargin's primary mechanism is the inhibition of sarco/endoplasmic reticulum calcium ATPase, leading to endoplasmic reticulum stress and cell death in various cancer types. Despite these effects, thapsigargin's non-specific cytotoxicity results in significant side effects, including organ damage and histamine-related reactions. Recent advances in targeted delivery, especially with the prodrug mipsagargin, initially suggested promise in minimizing these toxicities by selectively activating in cancer cells expressing prostate-specific membrane antigen (PSMA). However, the completion of clinical trials with no ongoing studies suggests that the viability of mipsagargin and other prodrugs remains uncertain, especially in light of the toxicities observed. While thapsigargin and its derivatives present a potential pathway in cancer treatment, their future role in oncology requires careful re-evaluation.

Cancer is a global concern worldwide. Prostate cancer has high prevalence and mortality rates among men. Photodynamic therapy (PDT) is an alternative treatment that is promising and effective with fewer side-effects than conventional therapies. However, some factors may limit its efficacy. For this, PDT can be combined with other modalities such as photobiomodulation (PBM) which is commonly used for increased cell proliferation/differentiation and wound healing. In this study, PBM pre-treatment at 655 nm of wavelength with 1, 3, and 5 J/cm² energy densities was applied to prostate cancer cells to investigate its role in indocyanine green (ICG)-mediated PDT applications. Following PBM treatment, various analyses were assessed including cell viability, cellular uptake of ICG, ATP production, nitric oxide release, reactive oxygen species generation, and the changes in mitochondrial membrane potential. Increased cell death was observed with the PBM pre-treatment at 1 and 3 J/cm² energy densities depending on ICG incubation time. Intracellular ROS generation and nitric oxide release by PBM had a significant impact on anticancer PDT action. An enhanced anticancer PDT effect was obtained with the PBM pre-treatment which may become a valuable modality to increase the sensitivity of the cancerous cells to PDT applications.

Background: Pancreatic ductal adenocarcinomas (PDAC) are huge threat to human for the extreme malignancy. PRIM2 was reported as tumor marker, while the functions and regulatory mechanisms in PDAC are still unclear. The study aimed to investigate the function of PRIM2 in PDAC.

Methods: Expression was detected using immunohistochemistry (IHC), Western blot, and real-time quantitative PCR (RT-qPCR) methods. Cell assays and xenograft model confirmed the phenotypes. Co-Immunoprecipitation (Co-IP) and protein stability assays were used for protein interactions.

Results: Inhibiting PRIM2 resulted in decreased proliferation and migration both in vitro and in vivo. PRIM2 upregulated FAM111B at increased RNA levels and protein stability.

Conclusion: PRIM2/FAM111B axis promoted proliferation and migration by modulating the PI3K/AKT and epithelial-mesenchymal transition (EMT) markers. The axis has the potential to be targeted for PDAC treatment.

Recent advancements in cancer immunotherapy have spotlighted the PD-1/PD-L1 pathway, crucial for its role in immune checkpoint regulation. Traditional inhibitors, though successful, face challenges like resistance and adverse effects. Bispecific antibodies targeting PD-1 and PD-L1 present a ground-breaking solution by simultaneously engaging multiple immune regulatory molecules. Developments in PD-1/PD-L1 bispecific antibodies up to now have been summarized, and the latest findings from the 2024 ASCO conference are presented, revealing that bispecific antibodies exhibit robust efficacy in treating various types of cancers, marking a significant step forward in cancer treatment.

Cancer progression is primarily driven by the uncontrolled activation of cellular signaling pathways, with the PI3K/Akt/mTOR (PAMT) pathway playing a central role. This pathway significantly contributes to the proliferation and survival of cancer cells, and its hyperactivity is a major challenge in managing several types of malignancies. This article delves into the promising potential of carotenoids, natural pigments found in abundance in fruits and vegetables, as a novel therapeutic strategy for cancer treatment. By specifically targeting and inhibiting the PAMT pathway, carotenoids may effectively disrupt the growth and survival of cancer cells. The article examines the complex mechanisms underlying these interactions and highlights the obstacles faced in cancer treatment. It proposes a compelling approach to developing therapies that leverage natural products to target this critical pathway, offering a fresh perspective on cancer treatment. Further research is essential to enhance the therapeutic efficacy of these compounds.