Jacob J Adashek, Jillian A Moran, Dung T Le, Razelle Kurzrock
{"title":"Lessons learned from a decade of immune checkpoint inhibition: The good, the bad, and the ugly.","authors":"Jacob J Adashek, Jillian A Moran, Dung T Le, Razelle Kurzrock","doi":"10.1007/s10555-025-10260-8","DOIUrl":"10.1007/s10555-025-10260-8","url":null,"abstract":"<p><p>Discovering the brakes/checkpoints that cancer places on the immune system to prevent being eradicated led to the 2018 Nobel Prize and the development of multiple Food and Drug Administration-approved immune checkpoint inhibitors (ICIs). ICIs have transformed the treatment of numerous cancer types and, remarkably, some patients with end-stage metastatic disease can achieve durable, complete remissions - cures. Still, ICIs cause significant immune-related toxicities, and most tumors are resistant. Unusual progression patterns such as pseudo-progression and hyper-progression (accelerated progression) can occur. Biomarkers for ICI response/resistance include microsatellite instability, high tumor mutational burden, and PD-L1 immunohistochemistry positivity; but they are imperfect, perhaps because of immune system complexity. Herein, we explore the good, the bad, and the ugly of ICIs in cancer treatment.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 2","pages":"43"},"PeriodicalIF":7.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microbiota and cancer: unraveling the significant influence of microbial communities on cancer treatment.","authors":"R Paul Wilson, Lori Rink, Çagla Tükel","doi":"10.1007/s10555-025-10256-4","DOIUrl":"https://doi.org/10.1007/s10555-025-10256-4","url":null,"abstract":"","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 2","pages":"42"},"PeriodicalIF":7.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prostate cancer-specific proinflammatory cytokines and chemokines impact on cancer stem cell development, lineage plasticity and heterogeneity in an Ancestral/racially diverse population: review.","authors":"Powell Isaac, Hudson Cullen, Teslow Emily, Heath Elisabeth, Raz Avraham, Bollig-Fischer Aliccia","doi":"10.1007/s10555-025-10259-1","DOIUrl":"https://doi.org/10.1007/s10555-025-10259-1","url":null,"abstract":"<p><p>Since 1976, Surveillance Epidemiology End Results (SEER) began collecting ethnicity data for the National Cancer Institute. The incidence of prostate cancer (PCa) among African American men (AAM) has been 60-70% higher than any other ethnicity and mortality rate 2 to 3 times greater than European American men (EAM), and those data have not changed. We reported in 2010 that PCa grows faster among AAM compared to EAM. In 2013, we utilized bioinformatics and ingenuity gene network analysis and in silico analysis to identify driver genes responsible for \"racial\" disparity. Genes associated with lipid metabolism were more expressed among EAM and genes associated with inflammation were more expressed among AAM. In 2021, we unraveled the network of the Ingenuity gene analysis and reported that the inflammatory genes, specifically proinflammatory cytokines and chemokines initiated multiple pathways. A literature review of these pathways showed that they induce castrate-resistant PCa (CRPC), metastasis, oxidative stress, DNA damage, cancer stem cells, lineage plasticity, and tumor heterogeneity. These genes and processes will be discussed in detail as to how they are initiated by proinflammatory cytokines and chemokines and how they act in a domino effect. Most importantly, how lineage plasticity changes the chemistry of the cancer stem cells of the original PCa so that it is no longer recognized by current therapy, chemotherapy, and immunotherapy. This suggests a paradigm change of current therapy is necessary to significantly reduce mortality of advanced PCa.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 2","pages":"41"},"PeriodicalIF":7.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"VCAM-1 as a common biomarker in inflammatory bowel disease and colorectal cancer: unveiling the dual anti-inflammatory and anti-cancer capacities of anti-VCAM-1 therapies.","authors":"Jessica R Pickett, Yuao Wu, Hang Thu Ta","doi":"10.1007/s10555-025-10258-2","DOIUrl":"10.1007/s10555-025-10258-2","url":null,"abstract":"<p><p>Vascular cell adhesion molecule (VCAM)-1 has garnered significant research attention due to its potential as a disease biomarker and drug target across several inflammatory pathologies-including atherosclerosis, asthma, rheumatoid arthritis, and inflammatory bowel disease (IBD). The VCAM-1 protein has also been noted for its functional involvement in cancer metastasis and drug resistance to conventional chemotherapeutics. Although the anti-inflammatory and anti-cancer facets of VCAM-1 antagonisation have been examined separately, there is yet to be a review that explicitly addresses the functional interrelationship between these mechanisms. Furthermore, the pleiotropic mechanisms of anti-VCAM-1 therapies may present a useful paradigm for designing drug candidates with synergistic anti-inflammatory and anti-tumorigenic effects. The pathological overlap between inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CRC) serves as the quintessential disease model to observe this therapeutic duality. This review thereby details the adhesive mechanisms of VCAM-1 in colorectal disease-specifically, driving immune cell infiltration during IBD and tumour cell metastasis in CRC-and posits the potential of this receptor as a common drug target for both diseases. To explore this hypothesis, the current progress of novel VCAM-1-directed drug candidates in experimental models of IBD and CRC is also discussed.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 2","pages":"40"},"PeriodicalIF":7.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Using ultrasound and microbubble to enhance the effects of conventional cancer therapies in clinical settings.","authors":"Deepa Sharma, Gregory J Czarnota","doi":"10.1007/s10555-025-10255-5","DOIUrl":"10.1007/s10555-025-10255-5","url":null,"abstract":"<p><p>It has been demonstrated in preclinical research that the administration of microbubbles with ultrasound can augment the proapoptotic sphingolipid pathway and enhance chemotherapy or radiation therapy-induced vascular endothelial disruption resulting in enhanced tumor cell death. Specifically, ultrasound-stimulated microbubbles (USMB) can increase blood vessel permeability facilitating the release of therapeutic substances in the target area. USMB can also serve as a potential radiation enhancing therapy as USMB exposure increases tumor cell death significantly as observed in preclinical models. Clinical studies have found the combination of USMB and these existing cancer therapies to be safe and also to be associated with greater tumor responses. USMB-based treatment can be applicable in a clinical setting using either ultrasound imaging or magnetic resonance imaging (MRI) guidance for precise treatment. In the latter, the ultrasound device is integrated into the MRI system platform for sonication to facilitate microbubble stimulation. In this review, we concisely present findings related to USMB and existing cancer therapies (chemotherapy and radiation therapy) in clinical trial settings. The possible underlying mechanism involved in USMB-enhanced chemotherapy or radiotherapy enhancement is also discussed. Lastly, the study concludes with some limitations and an examination of the future direction of these combined therapies.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"39"},"PeriodicalIF":7.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdulaziz Ahmed A Saad, Kun Zhang, Qianqian Deng, Jiawang Zhou, Lichen Ge, Hongsheng Wang
{"title":"The functions and modifications of tRNA-derived small RNAs in cancer biology.","authors":"Abdulaziz Ahmed A Saad, Kun Zhang, Qianqian Deng, Jiawang Zhou, Lichen Ge, Hongsheng Wang","doi":"10.1007/s10555-025-10254-6","DOIUrl":"10.1007/s10555-025-10254-6","url":null,"abstract":"<p><p>Recent progress in noncoding RNA research has highlighted transfer RNA-derived small RNAs (tsRNAs) as key regulators of gene expression, linking them to numerous cellular functions. tsRNAs, which are produced by ribonucleases such as angiogenin and Dicer, are classified based on their size and cleavage positions. They play diverse regulatory roles at the transcriptional, post-transcriptional, and translational levels. Furthermore, tRNAs undergo various modifications that influence their biogenesis, stability, functionality, biochemical characteristics, and protein-binding affinity. tsRNAs, with their aberrant expression patterns and modifications, act as both oncogenes and tumor suppressors. This review explores the biogenetic pathways of tsRNAs and their complex roles in gene regulation. We then focus on the importance of RNA modifications in tsRNAs, evaluating their impact on the biogenesis and biological functions on tsRNAs. Furthermore, we summarize recent data indicating that tsRNAs exhibit varied expression profiles across different cancer types, highlighting their potential as innovative biomarkers and therapeutic targets. This discussion integrates both existing and new knowledge about tsRNAs, emphasizing their importance in cancer biology and clinical advancement.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"38"},"PeriodicalIF":7.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amila Suraweera, Kenneth J O'Byrne, Derek J Richard
{"title":"Epigenetic drugs in cancer therapy.","authors":"Amila Suraweera, Kenneth J O'Byrne, Derek J Richard","doi":"10.1007/s10555-025-10253-7","DOIUrl":"10.1007/s10555-025-10253-7","url":null,"abstract":"<p><p>Genetic and epigenetic modifications of DNA are involved in cancer initiation and progression. Epigenetic modifications change chromatin structure and DNA accessibility and thus affect DNA replication, DNA repair and transcription. Epigenetic modifications are reversible and include DNA methylation, histone acetylation and histone methylation. DNA methylation is catalysed by DNA methyltransferases, histone acetylation and deacetylation are catalysed by histone acetylases and deacetylases, while histone methylation is catalysed by histone methyltransferases. Epigenetic modifications are dysregulated in several cancers, making them cancer therapeutic targets. Epigenetic drugs (epi-drugs) which are inhibitors of epigenetic modifications and include DNA methyltransferase inhibitors (DNMTi), histone deacetylase inhibitors (HDACi), histone methyltransferase inhibitors (HMTi) and bromodomain and extra-terminal motif protein inhibitors (BETi), have demonstrated clinical success as anti-cancer agents. Furthermore, the combination of epi-drugs with standard chemotherapeutic agents has demonstrated promising anti-cancer effects in pre-clinical and clinical settings. In this review, we discuss the role of epi-drugs in cancer therapy and explore their current and future use in combination with other anti-cancer agents used in the clinic. We further highlight the side effects and limitations of epi-drugs. We additionally discuss novel delivery methods and novel tumour epigenetic biomarkers for the screening, diagnosis and development of personalised cancer treatments, in order to reduce off-target toxicity and improve the specificity and anti-tumour efficacy of epi-drugs.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"37"},"PeriodicalIF":7.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ferroptosis: iron release mechanisms in the bioenergetic process.","authors":"Jaewang Lee, Jong-Lyel Roh","doi":"10.1007/s10555-025-10252-8","DOIUrl":"10.1007/s10555-025-10252-8","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of cell death, has been the focus of extensive research over the past decade, leading to the elucidation of key molecules and mechanisms involved in this process. While several studies have highlighted iron sources for the Fenton reaction, the predominant mechanism for iron release in ferroptosis has been identified as ferritinophagy, which occurs in response to iron starvation. However, much of the existing literature has concentrated on lipid peroxidation rather than on the mechanisms of iron release. This review proposes three distinct mechanisms of iron mobilization: ferritinophagy, reductive pathways with selective gating of ferritin pores, and quinone-mediated iron mobilization. Notably, the latter two mechanisms operate independently of iron starvation and rely primarily on reductants such as NADH and O<sub>2</sub>•<sup>-</sup>. The inhibition of the respiratory chain, particularly under the activation of α-ketoglutarate dehydrogenase, leads to the accumulation of these reductants, which in turn promotes iron release from ferritin and indirectly inhibits AMP-activated protein kinase through excessive iron levels. In this work, we delineate the intricate relationship between iron mobilization and bioenergetic processes under conditions of oxidative stress. Furthermore, this review aims to enhance the understanding of the connections between ferroptosis and these mechanisms.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"36"},"PeriodicalIF":7.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aiarpi Ezdoglian, Michel Tsang-A-Sjoe, Fatemeh Khodadust, George Burchell, Gerrit Jansen, Tanja de Gruijl, Mariette Labots, Conny J van der Laken
{"title":"Monocyte-related markers as predictors of immune checkpoint inhibitor efficacy and immune-related adverse events: a systematic review and meta-analysis.","authors":"Aiarpi Ezdoglian, Michel Tsang-A-Sjoe, Fatemeh Khodadust, George Burchell, Gerrit Jansen, Tanja de Gruijl, Mariette Labots, Conny J van der Laken","doi":"10.1007/s10555-025-10246-6","DOIUrl":"10.1007/s10555-025-10246-6","url":null,"abstract":"<p><p>The efficacy and off-target effects of immune checkpoint inhibitors (ICI) in cancer treatment vary among patients. Monocytes likely contribute to this heterogeneous response due to their crucial role in immune homeostasis. We conducted a systematic review and meta-analysis to evaluate the impact of monocytes on ICI efficacy and immune-related adverse events (irAEs) in patients with cancer. We systematically searched PubMed, Web of Science, and Embase for clinical studies from January 2000 to December 2023. Articles were included if they mentioned cancer, ICI, monocytes, or any monocyte-related terminology. Animal studies and studies where ICIs were combined with other biologics were excluded, except for studies where two ICIs were used. This systematic review was registered with PROSPERO (CRD42023396297) prior to data extraction and analysis. Monocyte-related markers, such as absolute monocyte count (AMC), monocyte/lymphocyte ratio (MLR), specific monocyte subpopulations, and m-MDSCs were assessed in relation to ICI efficacy and safety. Bayesian meta-analysis was conducted for AMC and MLR. The risk of bias assessment was done using the Cochrane-ROBINS-I tool. Out of 5787 studies identified in our search, 155 eligible studies report peripheral blood monocyte-related markers as predictors of response to ICI, and 32 of these studies describe irAEs. Overall, based on 63 studies, a high MLR was a prognostic biomarker for short progression-free survival (PFS) and overall survival (OS) hazard ratio (HR): 1.5 (95% CI: 1.21-1.88) and 1.52 (95% CI:1.13-2.08), respectively. The increased percentage of classical monocytes was an unfavorable predictor of survival, while low baseline rates of monocytic myeloid-derived suppressor cells (m-MDSCs) were favorable. Elevated intermediate monocyte frequencies were associated but not significantly correlated with the development of irAEs. Baseline monocyte phenotyping may serve as a composite biomarker of response to ICI; however, more data is needed regarding irAEs. Monocyte-related variables may aid in risk assessment and treatment decision strategies for patients receiving ICI in terms of both efficacy and safety.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"35"},"PeriodicalIF":7.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondrial alterations and signatures in hepatocellular carcinoma.","authors":"Tsung-Hsien Chen, Shu-Hsien Lin, Ming-Yang Lee, Hsiang-Chen Wang, Kun-Feng Tsai, Chu-Kuang Chou","doi":"10.1007/s10555-025-10251-9","DOIUrl":"10.1007/s10555-025-10251-9","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide. Its primary risk factors are chronic liver diseases such as metabolic fatty liver disease, non-alcoholic steatohepatitis, and hepatitis B and C viral infections. These conditions contribute to a specific microenvironment in liver tumors which affects mitochondrial function. Mitochondria are energy producers in cells and are responsible for maintaining normal functions by controlling mitochondrial redox homeostasis, metabolism, bioenergetics, and cell death pathways. HCC involves abnormal mitochondrial functions, such as accumulation of reactive oxygen species, oxidative stress, hypoxia, impairment of the mitochondrial unfolded protein response, irregularities in mitochondrial dynamic fusion/fission mechanisms, and mitophagy. Cell death mechanisms, such as necroptosis, pyroptosis, ferroptosis, and cuproptosis, contribute to hepatocarcinogenesis and play a significant role in chemoresistance. The relationship between mitochondrial dynamics and HCC is thus noteworthy. In this review, we summarize the recent advances in mitochondrial alterations and signatures in HCC and attempt to elucidate its molecular biology. Here, we provide an overview of the mitochondrial processes involved in hepatocarcinogenesis and offer new insights into the molecular pathology of the disease. This may help guide future research focused on improving patient outcomes using innovative therapies.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"34"},"PeriodicalIF":7.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}