Cancer and Metastasis Reviews最新文献

Prostate cancer (PCa) is one of the most commonly diagnosed malignancies and main causes of cancer-related deaths worldwide. It is characterized by high heterogeneity, ranging from slow-growing tumor to metastatic disease. Since both therapy selection and outcome strongly rely on appropriate patient stratification, it is crucial to differentiate benign from more aggressive conditions using new and improved diagnostic and prognostic biomarkers. Extracellular vesicles (EVs) are membrane-coated particles carrying a specific biological cargo composed of nucleic acids, proteins, and metabolites. Here, we provide an overview of the role of EVs in PCa, focusing on both their biological function and clinical value. Specifically, we summarize the oncogenic role of EVs in mediating the interactions with PCa microenvironment as well as the horizontal transfer of metastatic traits and drug resistance between PCa cells. Furthermore, we discuss the potential usage of EVs as innovative tools for PCa diagnosis and prognosis.

Colorectal cancer (CRC) is a common cancer, with a concerning rise in early-onset CRC cases, signalling a shift in disease epidemiology. Whilst our understanding of the molecular underpinnings of CRC has expanded, the complexities underlying its initiation remain elusive, with emerging evidence implicating the microbiome in CRC pathogenesis. This review synthesizes current knowledge on the intricate interplay between the microbiome, tumour microenvironment (TME), and molecular pathways driving CRC carcinogenesis. Recent studies have reported how the microbiome may modulate the TME and tumour immune responses, consequently influencing cancer progression, and whilst specific bacteria have been linked with CRC, the underlying mechanisms remains poorly understood. By elucidating the functional links between microbial landscapes and carcinogenesis pathways, this review offers insights into how bacteria orchestrate diverse pathways of CRC development, shedding light on potential therapeutic targets and personalized intervention strategies.

Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical involvement of specific mitochondrial-associated events, including mitochondrial quality control, intercellular mitochondrial transfer, and mitochondrial genetics, in potentiating the metastatic cascade of neoplastic cells. Furthermore, numerous recent studies have consistently emphasized the highly significant role mitochondria play in coordinating the regulation of tumor-infiltrating immune cells and immunotherapeutic interventions. This review provides a comprehensive and rigorous scholarly investigation of this subject matter, exploring the intricate mechanisms by which mitochondria contribute to tumor metastasis and examining the progress of mitochondria-targeted cancer therapies.

The mitochondrion is an essential cell organelle known as the powerhouse of the cell. Mitochondrial ribosomal proteins (MRPs) are nuclear encoded, synthesised in the cytoplasm but perform their main functions in the mitochondria, which includes translation, transcription, cell death and maintenance. However, MRPs have also been implicated in cancer, particularly advanced disease and metastasis across a broad range of cancer types, where they play a central role in cell survival and progression. For some, their altered expression has been investigated as potential prognostic markers, and/or therapeutic targets, which is the focus of this review. Several therapies targeting MRPs are currently approved by the Food and Drug Administration and the European Medicines Agency for use in other diseases, revealing the opportunity for repurposing their use in advanced and metastatic cancer. Herein, we review the evidence supporting key MRPs as molecular drivers of advanced disease in multiple cancer types. We also highlight promising avenues for future use of MRPs as precision targets in the treatment of late-stage cancers for which there are currently very limited effective treatment options.

The expression "lost at sea" means to be confused or perplexed. By extension, lost at SCLC references the current confusion about how to circumvent the chemoresistance, particularly platinum resistance, which so plagues the treatment of extensive-stage small cell lung cancer (ES-SCLC) that in 2012 the US National Cancer Institute (NCI) designated it a "recalcitrant cancer." Over a decade later, despite the approval of immune checkpoint inhibitors and the conditional approval of lurbinectedin, the prognosis for ES-SCLC, and especially platinum-resistant ES-SCLC, has scarcely improved. The focus of this review, which briefly summarizes current treatment options for ES-SCLC, is on five clinical-stage therapies with the potential to successfully reverse the platinum resistance that is perhaps the biggest obstacle to better clinical outcomes.

Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role of GLP-1R in type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, and facilitating insulin release. GLP-1R agonists have effectively managed obesity by reducing hunger, moderating food intake, and regulating body weight. Beyond diabetes and obesity, GLP-1R agonists exhibit a multifaceted impact on cancer progression across various malignancies. The mechanisms underlying these effects involve the modulation of signaling pathways associated with cell growth, survival, and metabolism. However, the current literature reveals a lack of in vivo studies on specific GLP-1R agonists such as semaglutide, necessitating further research to elucidate its precise mechanisms and effects, particularly in cancer. While other GLP-1R agonists have shown promising outcomes in mitigating cancer progression, the association between some GLP-1R agonists and an increased risk of cancer remains a topic requiring more profound investigation. This calls for more extensive research to unravel the intricate relationships between the GLP-1R agonist and different cancers, providing valuable insights for clinicians and researchers alike.

Membrane-associated RING-CH (MARCH) E3 ubiquitin ligases, a family of RING-type E3 ubiquitin ligases, have garnered increased attention for their indispensable roles in immune regulation, inflammation, mitochondrial dynamics, and lipid metabolism. The MARCH E3 ligase family consists of eleven distinct members, and the dysregulation of many of these members has been documented in several human malignancies. Over the past two decades, extensive research has revealed that MARCH E3 ligases play pivotal roles in cancer progression by ubiquitinating key oncogenes and tumor suppressors and orchestrating various signaling pathways. Some MARCH E3s act as oncogenes, while others act as tumor suppressors, and the majority of MARCH E3s play both oncogenic and tumor suppressive roles in a context-dependent manner. Notably, there is special emphasis on the sole mitochondrial MARCH E3 ligase MARCH5, which regulates mitochondrial homeostasis within cancer cells. In this review, we delve into the diverse functions of MARCH E3 ligases across different cancer types, shedding light on the underlying molecular mechanisms mediating their effects, their regulatory effects on cancer and their potential as therapeutic targets.

Paediatric patients with relapsed B cell acute lymphoblastic leukaemia (B-ALL) have poor prognosis, as relapse-causing clones are often refractory to common chemotherapeutics. While the molecular mechanisms leading to chemoresistance are varied, significant evidence suggests interactions between B-ALL blasts and cells within the bone marrow microenvironment modulate chemotherapy sensitivity. Importantly, bone marrow mesenchymal stem cells (BM-MSCs) and BM adipocytes are known to support B-ALL cells through multiple distinct molecular mechanisms. This review discusses the contribution of integrin-mediated B-ALL/BM-MSC signalling and asparagine supplementation in B-ALL chemoresistance. In addition, the role of adipocytes in sequestering anthracyclines and generating a BM niche favourable for B-ALL survival is explored. Furthermore, this review discusses the role of BM-MSCs and adipocytes in promoting a quiescent and chemoresistant B-ALL phenotype. Novel treatments which target these mechanisms are discussed herein, and are needed to improve dismal outcomes in patients with relapsed/refractory disease.

The coagulation system is known to play an important role in cancer development and metastasis, but the precise mechanisms by which it does so remain incompletely understood. With this in mind, we provide an updated overview of the effects of TFPI-2, a protease inhibitor, on cancer development and metastasis. TFPI-2 interacts with the thrombin cascade and also employs other mechanisms to suppress cancer growth and dissemination, which include extracellular matrix stabilization, promotion of caspase-mediated cell apoptosis, inhibition of angiogenesis and transduction of intracellular signals. Down-regulation of TFPI-2 expression is well documented in numerous types of neoplasms, mainly via promoter methylation. However, the exact role of TFPI-2 in cancer progression and possible approaches to up-regulate TFPI-2 expression warrant further studies. Strategies to reactivate TFPI-2 may represent a promising direction for future anticancer studies and therapy development.

Despite the great success that chimeric antigen receptor (CAR) T-cells have had in patients with B-cell malignancies and multiple myeloma, they continue to have limited efficacy against most solid tumors. Especially in the pediatric population, pre- and post-treatment biopsies are rarely performed due to ethical reasons, and thus, our understanding is still very limited regarding the mechanisms in the tumor microenvironment by which tumor cells exclude effectors and attract immune-suppressive cells. Nevertheless, based on the principles that are known, current T-cell engineering has leveraged some of these processes and created more potent CAR T-cells. The recent discovery of new oncofetal antigens and progress made in CAR design have expanded the potential pool of candidate antigens for therapeutic development. The most promising approaches to enhance CAR T-cells are novel CAR gating strategies, creative ways of cytokine delivery to the TME without enhancing systemic toxicity, and hijacking the chemokine axis of tumors for migratory purposes. With these new modifications, the next step in the era of CAR T-cell development will be the clinical validation of these promising preclinical findings.