Seminars In Oncology[JOURNAL]
Sun
200 papers
Prostate cancer in Türkiye: Trend analysis of incidence and mortality rates.
Turan G, Turan M, Basbinar Y … +1 more , Ellidokuz H
Semin Oncol · 2025 Oct · PMID 40684524 · Publisher ↗
Prostate cancer is a significant global health concern, with substantial regional variations in incidence and mortality rates. In Türkiye, it's the second most common cancer and fourth leading cause of cancer-related dea...
Prostate cancer is a significant global health concern, with substantial regional variations in incidence and mortality rates. In Türkiye, it's the second most common cancer and fourth leading cause of cancer-related deaths among men. This study aims to analyze trends in prostate cancer incidence and mortality rates in Türkiye. Prostate cancer trends in Türkiye is analyzed by using data of incidence from Türkiye Cancer Statistics Reports and mortality from TurkStat. Trends in incidence and mortality rates were analyzed using Joinpoint regression, evaluating average annual percentage changes and annual percentage change (APC). From 2004 to 2018, age-standardized prostate cancer incidence rate increased from 24.9 to 40.3 per 100,000, with the highest in aged 75 and older. The Annual Average Percentage Change (AAPC) was 2.6%[CI, 1.1 to 4.3] overall, with specific rates of 2.3% [CI, 0.5 to 3.5] in the 50-54 and -1.9% [CI, -3.7 to -0.1] in the 80-84 age group. The APC was 9.2% [CI, 3.6 to 24.8] from 2004 to 2008. From 2016-2018, APCs in 50-54 and 60-64 age groups are 13.4% [CI, 3.6 to 20.4] and 13.7% [CI, 0.4 to 23.6], respectively. Mortality rate ranged from 7.3 to 9.2 per 100,000 from 2009 to 2022, with a 4.9% [CI, 2.1 to 11.6] increase in 2009-2014 and a 1.9%-1.9%[CI, 4.4 to -0.6] decrease in 2014-2022. The incidence rate of prostate cancer in Türkiye increased until 2008, but then stabilised with the rates rising at the age of 50-54 and decreasing at the age of 80-84 years. Mortality rates initially increased but declined in the last 8 years. Further research is needed to explore factors influencing these trends.
Clinical efficacy and security analysis of DEB-TACE combined with trans arterial infusion of carrelizumab in the therapy of advanced liver cancer.
Chen Y, Zang X, Zhang X … +1 more , Zhang S
Semin Oncol · 2025 Oct · PMID 40680566 · Publisher ↗
To explore the clinical efficacy and security analysis of DEB-TACE combined with carrelizumab in the therapy of advanced liver cancer. This study was prospectively designed. Using a random number table method, 96 patient...
To explore the clinical efficacy and security analysis of DEB-TACE combined with carrelizumab in the therapy of advanced liver cancer. This study was prospectively designed. Using a random number table method, 96 patients with advanced liver cancer hospitalized from August 2022 to August 2023 were divided into the DT group (DEB-TACE treatment, n = 48) and the DT-C group (on the basis of the DT group, receiving carrelizumab infusion via hepatic artery, n = 48). The changes of therapeutic effect, serum tumor markers, T lymphocyte subsets, overall survival (OS) and progression-free survival (PFS) and the adverse effect were observed. The ORR and DCR of the DT-C group were higher than that of the DT group (P < 0.05). After 1 month of treatment, CD3, CD4 and CD4/CD8 were increased and the DT-C group was higher than the DT group (P < 0.001). The CD8+ decreased after 1 month of treatment, and the CD8+ in the DT-C group was significantly lower than that in the DT group (P < 0.001). AFP and PIVKA-II decreased after 1 month of treatment, and the DT-C group was lower than the DT group (P < 0.001). The overall survival (OS) (2-year survival rate 33.33%) and progression-free survival (PFS) (2-year survival rate 18.75%) of the DT-C group were higher than those of the DT group (P < 0.05). There was no difference in the adverse reaction incidence (P > 0.05). DEB-TACE combined with trans arterial infusion of carrelizumab is safe and effective in the treatment of advanced liver cancer. Compared with DEB-TACE alone, this combination therapy results in higher CD3+, CD4+, and CD4+/CD8+ levels, as well as reduced CD8+, AFP, and PIVKA-II levels.
Metabolic reprogramming: The driving force behind cancer drug resistance.
El-Sehrawy AAMA, Hsu CY, Alkhathami AG … +7 more , Chandra M, Basunduwah TS, Malathi H, Senapati JN, Gautam A, Kadhem M, Yasin HA
Semin Oncol · 2025 Oct · PMID 40674808 · Publisher ↗
Metabolic reprogramming enables stress adaptation of cancer cells to treatment and is a primary causative force of drug resistance. Dysregulation of glucose, amino acid, and lipid metabolism supplies energy, biosynthetic...
Metabolic reprogramming enables stress adaptation of cancer cells to treatment and is a primary causative force of drug resistance. Dysregulation of glucose, amino acid, and lipid metabolism supplies energy, biosynthetic precursors, and redox balance, promoting survival in the treated tumor. These processes are coordinated by oncogenic signaling, loss of tumor suppressors, and regulatory non-coding RNAs, which promote cancer stemness, immune evasion, and resistance to apoptosis. This review examines the mechanisms by which central metabolic pathways, particularly glycolysis, glutamine metabolism, and fatty acid synthesis, are altered to facilitate drug resistance in various types of cancer. Additionally, we report on novel therapeutic approaches that exploit such metabolic weaknesses to prevent therapy resistance and enhance clinical outcomes. Future directions emphasize the need for advanced metabolic profiling to personalize treatment approaches and the clinical translation of promising preclinical findings to overcome this significant obstacle in cancer therapy.
From tissue architecture to clinical insights: Spatial transcriptomics in solid tumor studies.
Sharma A, Raut SS, Shukla A … +3 more , Gupta S, Mishra A, Singh A
Semin Oncol · 2025 Oct · PMID 40664120 · Publisher ↗
Cancer is a highly heterogeneous disease, and its diagnosis, prognosis, and therapeutic responsiveness depend not only on genetic alterations but also on the intricate organization of cells within the tumor microenvironm...
Cancer is a highly heterogeneous disease, and its diagnosis, prognosis, and therapeutic responsiveness depend not only on genetic alterations but also on the intricate organization of cells within the tumor microenvironment (TME). Spatial transcriptomics-a suite of techniques that preserves the spatial context of gene expression in intact tissue-has revolutionized our ability to decipher tumor architecture and intercellular communication. This review provides an in-depth analysis of recent advancements in spatial transcriptomics technologies and their applications in solid tumor research. We first describe the evolution of spatial transcriptomics from early in situ hybridization methods to state-of-the-art imaging- and sequencing-based platforms. Next, we discuss how spatially resolved transcriptomics is transforming cancer research by revealing the molecular landscapes of tumor cores, invasive edges, and immunological niches. The integration of spatial transcriptomics with single-cell multiomics and advanced computational algorithms is leading to the identification of novel prognostic and predictive biomarkers. Despite tremendous progress, challenges remain in terms of technical resolution, data processing, sample preparation, and clinical standardization. Finally, we highlight emerging trends-including three-dimensional (3D) spatial profiling, multimodal integration, and the use of artificial intelligence and Deep learning-to envision a future in which spatial transcriptomics will serve as a pivotal tool for precision oncology. Together, these developments promise to refine cancer biomarker studies and ultimately improve patient outcomes.
Multiple myeloma: Insights into underlying mechanisms, advances in diagnostic and therapeutic modalities.
Yadav R, Chaudary JK, Bisht K … +4 more , Dhamija P, Chaudhary PK, Nath UK, Jain N
Semin Oncol · 2025 Oct · PMID 40644751 · Publisher ↗
Multiple myeloma (MM) is characterized by malignant proliferation and accumulation of terminally differentiated antibody-producing plasma cells in bone marrow. The underlying genetic causes of MM are highly complex, invo...
Multiple myeloma (MM) is characterized by malignant proliferation and accumulation of terminally differentiated antibody-producing plasma cells in bone marrow. The underlying genetic causes of MM are highly complex, involving the loss of function in a myriad of crucial genes, especially those involved in DNA replication fidelity and repair. The important genetic events underscoring MM mutagenesis entail large-scale chromosomal aberrations, localized genetic changes, defective DNA repair mechanisms, point mutation, and mutagenic activity of enzymes such as activation-induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, and catalytic polypeptide (APOBEC). Despite considerable improvement in treatment regimen, MM disease remains incurable for majority of patients with very high mortality. Notably, delay in diagnosis of MM could indirectly contribute to the worse clinical outcomes and lower treatment responsiveness through several mechanisms. Primarily, MM diagnosis relies on histopathological changes and molecular profiling of the patient's sample. In the past decades, new methods of MM diagnosis and therapeutic approaches have been invented. Together, advances in disease understanding, diagnosis, and novel effective therapeutic interventions have substantially helped slow down and/or arresting the disease progression in the large number of patients, thereby increasing overall survival. This review discusses the genetic causes of MM, clinical presentation, advances in diagnosis, and new therapeutic interventions, including combinations of effective agents targeting relapse/refractory MM.
LncRNA THUMPD3-AS1 promotes the proliferation and migration of esophageal cancer cells through the miR-29a-3p/ELK1/PRDX4 signaling pathway.
Tang M, Sun J, Cai Z
Semin Oncol · 2025 Aug · PMID 40639318 · Publisher ↗
Esophageal cancer (ESCA) is a significant contributor to cancer-related deaths worldwide due to its aggressive nature and poor prognosis. Recent research indicates that non-coding RNAs are critical in tumor progression....
Esophageal cancer (ESCA) is a significant contributor to cancer-related deaths worldwide due to its aggressive nature and poor prognosis. Recent research indicates that non-coding RNAs are critical in tumor progression. This study intends to explore the interaction between LncRNA THUMPD3-AS1 and miR-29a-3p in ESCA advancement. By conducting bioinformatic analyses and validating differentially expressed genes in ESCA clinical samples, the regulatory relationship between THUMPD3-AS1, miR-29a-3p, ETS transcription factor (ELK1), and Peroxiredoxin 4 (PRDX4) was investigated using various functional assays. In vitro and in vivo experiments were also carried out to assess the impact of this interaction on tumor growth and ESCA progression. Results indicated elevated levels of THUMPD3-AS1 in ESCA tissues, acting as a sponge for miR-29a-3p, a microRNA known for its tumor-suppressive properties. This interaction relieved miR-29a-3p's inhibition of ELK1, resulting in increased PRDX4 expression. Functional tests confirmed that the THUMPD3-AS1/miR-29a-3p/ELK1/PRDX4 axis supports tumor proliferation, migration, and invasion in ESCA. Further validation of these findings was done through in vivo experiments. In conclusion, this study underscores the significance of the THUMPD3-AS1/miR-29a-3p/ELK1/PRDX4 axis as a crucial regulatory pathway in ESCA, unveiling its oncogenic role in enhancing tumor aggressiveness.
MicroRNAs: From Bench to Bedside Applications as Breast Cancer Therapeutics.
Samad MA, Ahmad I, Asghar MN … +7 more , Suhail M, Rehan M, Al-Abbasi FA, Alsolami K, Akhter MS, Ahmad A, Tabrez S
Semin Oncol · 2025 Oct · PMID 40616959 · Publisher ↗
MicroRNAs (miRNAs) or small noncoding RNA molecules, 18-22 nucleotides long, are evolutionarily conserved and may have an impact on the behavior and progression of tumors. Cancer initiation, proliferation, invasion, and...
MicroRNAs (miRNAs) or small noncoding RNA molecules, 18-22 nucleotides long, are evolutionarily conserved and may have an impact on the behavior and progression of tumors. Cancer initiation, proliferation, invasion, and metastasis are all related to the specific deregulation of miRNAs. It also affects the genes involved in metabolism, apoptosis, cellular differentiation, and proliferation. Understanding the functional roles of miRNAs could shed light on the intricate molecular mechanism that underlie cancer growth. The purpose of this review is to investigate the presence of tumor-suppressive, oncogenic, and metastatic miRNAs in cancer cells, specifically breast cancer (BC) and how these miRNAs affect the development of BC and its subtypes. In addition, the miRNA-based therapeutic strategies and utilization of different delivery system to enhance the efficacy has also been covered. Based on our article, miRNAs appear to be cutting-edge prognostic, therapeutic, and diagnostic tools for the treatment of BC. However, several barriers, such as, delivery systems, side effects, demographic variabilities, and lengthy clinical studies needs to be optimized before these miRNAs could be routinely used in clinical settings.
Baicalein and baicalin in cancer therapy: Multifaceted mechanisms, preclinical evidence, and translational challenges.
Capó X, Kumar R, Mishra AP … +9 more , Nigam M, Waranuch N, Martorell M, Sharopov F, Calina D, Popa D, Setzer WN, Sharifi-Rad J, Pezzani R
Semin Oncol · 2025 Oct · PMID 40614344 · Publisher ↗
Natural compounds with multitargeted actions are gaining prominence in oncology for their potential to complement and transcend the limitations of conventional therapies. Among them, baicalein and baicalin, two flavonoid...
Natural compounds with multitargeted actions are gaining prominence in oncology for their potential to complement and transcend the limitations of conventional therapies. Among them, baicalein and baicalin, two flavonoids primarily isolated from Scutellaria baicalensis, have attracted attention for their broad-spectrum anticancer properties. This review synthesizes current evidence from cellular systems, animal models, and early-phase clinical studies, exploring their pharmacological potential and translational relevance. Both molecules interfere with key hallmarks of cancer, including proliferation, survival, angiogenesis, metastasis, and immune evasion. Mechanistically, they modulate interconnected signaling cascades governing apoptosis, inflammation, and cell cycle control, and they enhance tumor sensitivity to chemotherapy and radiotherapy. In-vivo models consistently demonstrate tumor growth inhibition, while clinical data suggest a favorable safety profile, even at relatively high oral doses. However, their clinical translation remains hampered by limited solubility, poor oral bioavailability, and rapid metabolism, factors that continue to constrain their therapeutic window. Efforts to overcome these barriers through structural modification, encapsulation strategies, and advanced delivery systems are underway, yet few have advanced beyond preclinical validation. Despite these pharmacokinetic limitations, baicalein and baicalin remain compelling candidates for integrative oncological approaches. Their pleiotropic mechanisms, combined with low toxicity and synergistic behavior with standard therapies, position them as prototypes for a new generation of phytochemical-based anticancer agents. Continued work is needed to resolve formulation challenges and define precise molecular targets, but their trajectory reflects the growing scientific and clinical momentum around rationally designed natural compound therapeutics.
Breaking barriers: Deciphering the mechanisms of Olaparib resistance in prostate cancer.
El-Sehrawy AAMA, Mukhlif MY, Khalaf AA … +7 more , Uthirapathy S, Ballal S, Singh A, Kavitha V, Maharana L, Ridha-Salman H, Al-Altememe ARH
Semin Oncol · 2025 Aug · PMID 40578041 · Publisher ↗
A poly (ADP-ribose) polymerase (PARP) inhibitor, Olaparib has shown notable clinical effectiveness in treating metastatic castration-resistant prostate cancer (mCRPC) with DNA damage repair gene mutations. Though initial...
A poly (ADP-ribose) polymerase (PARP) inhibitor, Olaparib has shown notable clinical effectiveness in treating metastatic castration-resistant prostate cancer (mCRPC) with DNA damage repair gene mutations. Though initial reactions were encouraging, the emergence of resistance poses a major clinical problem that reduces the long-term therapeutic value for patients. This paper thoroughly investigates the molecular processes behind acquired and intrinsic resistance to Olaparib in prostate cancer (PCa). Among the several resistance routes discovered are restoration of homologous recombination (HR) repair capacity via secondary BRCA2 mutations, loss of 53BP1/REV7/Shieldin complex activity, and activation of alternative DNA repair pathways. Recent studies further imply that changes in cell cycle checkpoints and epigenetic changes could help to increase therapy resistance even more. Knowing these several resistance mechanisms helps one to create reasonable combination strategies and biomarker-driven initiatives to defeat Olaparib resistance. Among the new treatment options are combination therapies aimed at compensatory DNA repair mechanisms, cell cycle checkpoint inhibitors, epigenetic modulators, and methods tackling tumor microenvironment elements. Predictive biomarker discovery of resistance will help to guide individual treatment choice and sequential therapy optimization, hence changing clinical results for advanced PCa patients in the precision medicine age.
Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment.
Ordóñez C, Zurita S, Ramírez G … +7 more , Cordeiro F, Garcia-Matamoros K, Huaman-Garaicoa F, Orellana-Manzano A, Sandoya-Onofre L, Pogo J, Carvajal-Aldaz D
Semin Oncol · 2025 Aug · PMID 40570572 · Publisher ↗
Cancer remains as one of the leading causes of death worldwide, emphasizing the need for innovative diagnostic and therapeutic tools. The gut microbiota has emerged as a factor that influences cancer progression, prognos...
Cancer remains as one of the leading causes of death worldwide, emphasizing the need for innovative diagnostic and therapeutic tools. The gut microbiota has emerged as a factor that influences cancer progression, prognosis, and treatment outcomes. This review analyzes observational and interventional studies conducted with human subjects over the past 5 years, highlighting significant advancements in gut microbiota research for cancer management. Observational studies consistently demonstrated differences in gut microbial composition between cancer patients and healthy controls. Moreover, microbial diversity, particularly at the species and strain level, correlated significantly with clinical outcomes. Interventional studies showed the potential of probiotics and fecal microbiota transplantation (FMT) as adjuncts in cancer therapy by restoring microbial diversity, reducing inflammation, and alleviating chemotherapy-induced complications. Collectively, these findings suggest the gut microbiota's potential as a tool for cancer care. Future research should focus on standardizing taxonomic-level analyses, optimizing probiotic formulations, and validating FMT/AFMT clinical protocols to fully harness the gut microbiota's diagnostic and therapeutic capabilities in oncology.
Peripheral blood CD4CD25 T lymphocytes and TGF-β predict the prognosis in relapsed/refractory multiple myeloma treated with daratumumab.
Xue H, Wei F, Li R
Semin Oncol · 2025 Aug · PMID 40570571 · Publisher ↗
For patients with relapsed/refractory multiple myeloma (R/RMM), it is indispensable to choose a combination regimen based on Daratumumab, a kind of CD38-targeting monoclonal antibody (mAb), which has prominent therapeuti...
For patients with relapsed/refractory multiple myeloma (R/RMM), it is indispensable to choose a combination regimen based on Daratumumab, a kind of CD38-targeting monoclonal antibody (mAb), which has prominent therapeutic advantages. However, a few patients still experienced rapid progression, and the predictors of prognosis are little known. Thus, we analyzed peripheral blood (PB) CD4CD25 T lymphocytes and transforming growth factor-β (TGF-β) of R/RMM patients before Daratumumab treatment, to clarify their correlation with survival. Flow cytometry (FCM) was employed to detect, analyze, and compare CD4CD25T lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify serum TGF-β. Clinical indicators were gathered and classified into quartiles. In R/RMM patients' PB, we compared these markers between the upper and lower three quartiles. We found that CD4CD25 T lymphocytes (pcs/µL) and TGF-β in the PB of the R/RMM patients were higher than those of the newly diagnosed MM (NDMM) patients. Additionally, serum TGF-β of R/RMM patients was positively correlated to serum creatinine (Scr) (P < 0.05). Finally, high CD4CD25 T lymphocytes (pcs/µL, 95% confidence interval [CI], 4.312-7.028, P = 0.001), CD4CD25 T lymphocytes (%, median PFS: 5.67 months, P = 0.043), and Scr (µmol/l, 95% CI, 5.378-7.422, P = 0.005) of R/RMM patients were significantly associated with inferior progression-free survival (PFS). These results suggest that patients with R/RMM are rich in CD4CD25 T lymphocytes and TGF-β. Additionally, R/RMM patients with elevated CD4CD25 T lymphocytes, TGF-β, and Scr before the treatment of daratumumab are more likely to have a poor prognosis.
Recent updates on novel heterocyclic scaffolds of anticancer potential as emerging tubulin inhibitors.
Kumar S, Gupta U, Singh RK
Semin Oncol · 2025 Aug · PMID 40561717 · Publisher ↗
Cancer remains a leading cause of mortality worldwide, accounting for approximately one in six deaths. Among the most prevalent cancer types are prostate, lung, colon, and rectal cancers. Despite significant investments...
Cancer remains a leading cause of mortality worldwide, accounting for approximately one in six deaths. Among the most prevalent cancer types are prostate, lung, colon, and rectal cancers. Despite significant investments in research, the therapeutic success of modern cancer treatments remains limited compared to other life-threatening diseases. In the pursuit of novel anticancer strategies, microtubules-dynamic cytoskeletal structures essential for cellular processes such as mitosis, intracellular transport, and signaling-have emerged as attractive drug targets. This review provides a comprehensive overview of recent advancements in the design and synthesis of novel heterocyclic scaffolds as tubulin inhibitors, emphasizing their potential as anticancer agents. Heterocyclic compounds exhibit unique therapeutic properties that disrupt microtubule dynamics, inducing cell cycle arrest and apoptosis in rapidly proliferating cancer cells. The article systematically classifies and critically evaluates diverse heterocyclic scaffolds, including both natural products and synthetic derivatives, with a focus on their interactions with the microtubule cytoskeleton at a molecular level. By consolidating current insights into these emerging scaffolds, this review serves as a valuable resource for the development of next-generation anticancer therapeutics targeting tubulin.
Unlocking the therapeutic potential of polyphenols: Promising advances and future directions in pancreatic cancer treatment.
Suhail M, Tabrez S, Tarique M … +4 more , Muhammad N, Rehan M, Zughaibi TA, Alhashmi MH
Semin Oncol · 2025 Aug · PMID 40553980 · Publisher ↗
Pancreatic cancer is one of the most lethal malignancies of the digestive tract, with a poor prognosis and a 5-year survival rate of less than 10%. The highly aggressive nature of pancreatic cancer results in a mortality...
Pancreatic cancer is one of the most lethal malignancies of the digestive tract, with a poor prognosis and a 5-year survival rate of less than 10%. The highly aggressive nature of pancreatic cancer results in a mortality rate of approximately 50% within the 6-month period of diagnosis. The absence of disease-specific symptoms significantly impedes early detection and timely intervention, contributing to its high mortality rate. Current treatment options such as radiotherapy, chemotherapy, and surgery are often inadequate for complete disease eradication and are associated with severe side effects that compromise patients' overall health. As a result, there is an urgent need for novel therapeutic strategies to address the rapidly increasing incidence of pancreatic cancer while ensuring safer, cost and more effective treatment alternatives. Plant-derived polyphenols have emerged as promising candidates due to their potent anticancer properties and minimal side effects compared to conventional therapies. In this review, we explore the biological significance and anticancer mechanisms of key polyphenols, including quercetin, resveratrol, apigenin, luteolin, EGCG, and curcumin, with a particular focus on their role in combating pancreatic cancer. Additionally, we provide a comprehensive summary of various pancreatic cancer studies, including ongoing clinical trials from the past decade.
Exosomal circular RNAs as drivers of temozolomide resistance in glioblastoma: Mechanisms and implications.
Theab EY, Alkhathami AG, Ridha Ali I … +6 more , Al-Hetty HRAK, Ballal S, Kalia R, Almalki SG, Arya R, Nathiya D
Semin Oncol · 2025 Aug · PMID 40553979 · Publisher ↗
Glioblastoma (GBM) continues to be 1 of the most malignant tumors with limited success in therapy, primarily owing to the emergence of resistance towards temozolomide TMZ. Resistance to TMZ is a multifactorial phenomenon...
Glioblastoma (GBM) continues to be 1 of the most malignant tumors with limited success in therapy, primarily owing to the emergence of resistance towards temozolomide TMZ. Resistance to TMZ is a multifactorial phenomenon in GBM, depending on the interactions between genetic, epigenetic, and microenvironmental factors. Noncoding RNAs, most significantly circRNAs, have recently been highlighted as playing important roles in the pathogenesis of GBM and drug resistance against TMZ. These stable, circular RNA molecules can act as microRNA sponges or encode functional peptides; hence, they modulate functions relating to different aspects of tumor development. Furthermore, circRNAs can be carried within exosomes, promoting intercellular communication and propagation of drug resistance. Exosomes serve as sophisticated delivery vehicles that harbor varying bioactive molecules like proteins, lipids, mRNAs, miRNAs, lncRNAs, and many others, including circular RNAs. This review elucidates the specific functions held by exosomal circRNAs, such as circASAP1 and circ-HIPK3, in the modulation of TMZ resistance through different molecular pathways. It also reflects the biomarker potential of exosomal circRNAs as diagnostics and prognostics, allowing their dynamic application in liquid biopsies to monitor the progression of GBM over time. This review tries to develop an understanding of the complex nature of mechanisms conferring resistance to TMZ, with a particular focus on new insights regarding the potential roles of exosomal circular RNAs.
Breast cancer exosomes: Managing macrophage polarization and immune regulation in the tumor microenvironment.
Mohammad SI, Theab EY, Vasudevan A … +7 more , Bishoyi AK, Ballal S, Al-Hetty HRAK, Shankhyan A, A A, Panigrahi R, Yasin HA
Semin Oncol · 2025 Aug · PMID 40540981 · Publisher ↗
Exosomes are sub-150 nm extracellular vesicles mediating intercellular messaging in breast cancer's complex tumor microenvironment (TME). Produced by both tumor cells and their stroma components, these vesicles excrete v...
Exosomes are sub-150 nm extracellular vesicles mediating intercellular messaging in breast cancer's complex tumor microenvironment (TME). Produced by both tumor cells and their stroma components, these vesicles excrete various biomolecules, such as microRNAs (miRNAs), proteins, lipids, and even DNA fragments, enabling a functional exchange of information among cells. In breast cancer, different studies indicate a significant role of exosome-mediated signaling in modulating the phenotype of tumor-associated macrophages (TAMs), mainly polarizing them toward an M2-like phenotype, further supporting the potentiality for tumor-promoting functions. This review will detail the diverse roles of breast cancer-derived exosomes and macrophage polarization and elaborate on their recognized pathways by which these vesicles casually alter the macrophage phenotype. In our discussion, we take a broad detour to deeply examine the unique molecular accessories delivered by breast cancer exosomes. In particular, we discuss the miRNAs suppressed by M1-associated gene expression and those endowing M2-related pathways with abilities, and we cover the proteins that activate pathways like the STAT3 and NF-κB pathways in macrophages. This review will also address the relevance of mechanistic issues to clinical manifestation in exosome-mediated macrophage polarization in breast cancer. Finally, targeting exosome-mediated macrophage polarization as a promising strategy to enhance antitumor immunity in conjunction with improving breast cancer outcomes is deliberated.
Advancing personalized medicine in LMICs: Predictive indicators for cervical cancer immunotherapy response.
Eksteen C, Riedemann J, van der Merwe FH … +2 more , Botha MH, Engelbrecht AM
Semin Oncol · 2025 Aug · PMID 40505389 · Publisher ↗
The World Health Organization reports that cervical cancer ranks as the eighth most common cancer worldwide and is the ninth leading cause of cancer-related deaths. It is also the most prevalent cancer among women in 25...
The World Health Organization reports that cervical cancer ranks as the eighth most common cancer worldwide and is the ninth leading cause of cancer-related deaths. It is also the most prevalent cancer among women in 25 countries, primarily in Sub-Saharan Africa. Consequently, cervical cancer continues to pose a significant global health challenge, particularly due to the limited treatment options available for advanced stages of the disease. Evidently, immunotherapy is a promising strategy, but its efficacy is variable among patients. As such, predictive indicators are essential for identifying patients who are most likely to benefit from immunotherapy and for guiding treatment decisions. This review provides an overview of the current landscape of predictive biomarkers in cervical cancer immunotherapy, including immune checkpoint molecules, tumor mutational burden and immune cell infiltration. We further discuss additional factors such as cytokines, tumor infiltrating lymphocytes and previous exposure to platinum-based chemotherapy. As the field continues to evolve, ongoing research efforts are needed to refine predictive biomarkers and optimize patient selection in LMICs for immunotherapy in cervical cancer.
Identifying and closing information gaps in head and neck cancer surgery.
Comess SR, Joseph JK, Yoon M … +6 more , Sayeed S, Borkhetaria P, Stanisce L, Brandwein-Weber M, Karasick M, Urken ML
Semin Oncol · 2025 Aug · PMID 40505388 · Publisher ↗
Contemporary cancer management relies on the precise transfer of information regarding disease and treatment details between a range of providers and facilities. The time of surgery is uniquely responsible for many ambig...
Contemporary cancer management relies on the precise transfer of information regarding disease and treatment details between a range of providers and facilities. The time of surgery is uniquely responsible for many ambiguities in this oncological information flow, as intraoperative communication and documentation are often unregimented and imprecise. Downstream providers such as radiation oncologists, medical oncologists, and radiologists rely on surgical pathology reports for planning postoperative treatment and surveillance. However, traditional pathology reports lack critical details about the actions taken during surgery and do not make the oncologic clearance status explicit. We identified agents of change to improve information transfer and designed an improved surgical workflow and pathology report that make use of a novel pathologic reporting software to address gaps in the oncologic care timeline. Our updated workflow results in a dynamic final pathology report that integrates annotated 3D scans of the surgical specimen and extirpative defect, unequivocal reconciliation of at-risk and supplemental margins, highlighted preoperative radiographs, and brief narrative summaries by the surgeon and pathologist. These tangible changes aim to improve clarity and continuity in oncologic care.
A 3-miRNA signature for noninvasive breast cancer detection.
Ebrahimi A, Ghavi D, Mirzaei Z … +4 more , Barati T, Shekari-Khaniani M, Gahramani-Almangadim H, Mansoori-Derakhshan S
Semin Oncol · 2025 Aug · PMID 40505387 · Publisher ↗
As a key component of epigenetics, microRNAs (miRNAs) have provided promising insights into several aspects of Breast Cancer (BC). We have analyzed 2 BC tissue microarray datasets (GSE26659 and GSE40525), as well as 2 se...
As a key component of epigenetics, microRNAs (miRNAs) have provided promising insights into several aspects of Breast Cancer (BC). We have analyzed 2 BC tissue microarray datasets (GSE26659 and GSE40525), as well as 2 serum datasets (GSE106817 and GSE113486). The results were then intersected to identify commonly dysregulated miRNAs in the tissue and serum of BC patients. RNA-seq analysis was then applied to The Cancer Genome Atlas (TCGA) data. Briefly, 79 dysregulated miRNAs were identified in the tissue and serum of patients with BC of which 3 significantly dysregulated and previously unstudied miRNAs, let-7e-5p, miR-151a-5p and miR-887-3p, were chosen for quantification in the serum of cancer patients by RT-PCR followed by evaluation of their diagnostic and prognostic features. RT-PCR analysis revealed overexpression of let-7e-5p (logFC = 2.01, P < .05) and miR-151a-5p (logFC = 1.48, P < .05) whereas miR-887-3p was downregulated (logFC = 0.62, P < .05) similar to microarray and RNA-seq data analysis. Based on regression analysis, a 3 miRNA-signature biomarker was proposed which had better diagnostic ability (AUC = 84.17%) compared to the ability of these miRNAs when assessed individually. Moreover, enrichment analysis revealed these miRNAs mediate vital cellular processes and biological functions that influence the development of cancer. Similarly, significant prognostic clinical characteristics were observed for these miRNAs. Overall, we have identified and validated a novel and proficient signature biomarker in serum of BC patients consisting of 3 miRNAs.
Atezolizumab plus bevacizumab versus Lenvatinib for patients with Barcelona clinic liver cancer stage B (BCLC-B) hepatocellular carcinoma (HCC): A real-world population.
Vitiello F, Tada T, Suda G … +23 more , Shimose S, Kudo M, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Yoo C, Lonardi S, Tovoli F, Kumada T, Scartozzi M, Tamburini E, Foschi FG, Persano M, Rossari F, Foti S, Camera S, De Cobelli F, Aldrighetti L, Cascinu S, Casadei-Gardini A, Rimini M
Semin Oncol · 2025 Aug · PMID 40494131 · Publisher ↗
BACKGROUND: The aim of the present study was to perform a real-world analysis on a large patient cohort with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) treated with atezolizumab plus be...
BACKGROUND: The aim of the present study was to perform a real-world analysis on a large patient cohort with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (A + B) or with Lenvatinib. METHODS: The study population included patients affected with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma not suitable for locoregional therapies (LRTs) from eastern and western populations, who received atezolizumab plus bevacizumab (A + B) or Lenvatinib as first-line treatment. Univariate and multivariate analyses were used to evaluate predictive factors for overall survival (OS) and time to progression (TTP) while prognostic factors were analyzed by univariate and multivariate analysis using Cox regression model. RESULTS: 919 patients with BCLC-B HCC were analyzed in the study. Lenvatinib was administered to 561 (61%) patients while 358 (39%) received A + B. The median overall survival (mOS) for patients receiving Lenvatinib was 21.3 months compared to 15.8 months for patients receiving A + B as first-line treatment (Lenvatinib v A + B), hazard ratio (HRs) 0.84 P = 0.22. The median time to progression (mTTP) for patients receiving Lenvatinib was 7.3 months compared to 8.7 months for patients receiving A + B as first-line treatment (Lenvatinib v A + B): HR 1.15 P = 0.10. Multivariate analysis confirmed no different in terms of mOS and mTTP between the two treatments. Objective response rate (ORR) was 47.1% for patients receiving Lenvatinib and 27.1% for patients receiving A + B P < 0.000001. Patients receiving Lenvatinib experienced a significantly higher incidence of hand-foot skin reaction (HFSR), hypertension, diarrhea, fatigue, decrease appetite, hypothyroidism, and other toxicity compared to patients receiving A + B. Favorable prognostic factors for OS in Lenvatinib group were platelets (PLT) >100.000 (HR 0.68 P = 0.02), HCC nonalcoholic steatohepatitis/nonalcoholic fatty liver disease (NASH/NAFLD) related (HR 0.53, P = 0.03). No favorable prognostic factors were found for A + B group. Favorable prognostic factors for TTP in the A + B group were in TACE refractory patients (HR 0.76, P = 0.02), PLT <100.000 (HR 0.62, P = 0.0067), and neutrophil-to-lymphocyte ratio (NLR) < 3 (HR 0.78, P = 0.04). CONCLUSION: Although Lenvatinib had a higher response rate, the study showed no statistically significant differences between Lenvatinib and A + B in terms of efficacy, in patients with BCLC-B HCC.
CTLA-4 blockade in ovarian cancer immunotherapy: Mechanisms and clinical strategies.
Hsu CY, Muhammed TM, Uthirapathy S … +7 more , Ahmad I, Ballal S, Kalia R, J P, Ray S, Mohsin RM, Abiess AAA
Semin Oncol · 2025 Aug · PMID 40482550 · Publisher ↗
Although studies have demonstrated that ovarian cancer cells can express immune checkpoint proteins like CTLA-4 and that higher levels of tumor-infiltrating lymphocytes are linked to better patient survival, clinical tri...
Although studies have demonstrated that ovarian cancer cells can express immune checkpoint proteins like CTLA-4 and that higher levels of tumor-infiltrating lymphocytes are linked to better patient survival, clinical trials utilizing immune checkpoint inhibitors in ovarian cancer have not yielded encouraging results. Tumor heterogeneity and innate or acquired resistance associated with the tumor microenvironment (TME) may account for the inadequate response to ICIs. Understanding tumor immunobiology, identifying biomarkers for patient selection, and formulating suitable treatment regimens remain challenging, yet these are the aspirations for the future use of immunotherapy in ovarian cancer. Induced T cells express CD80 and CD86, providing a positive costimulatory signal via CD28. CTLA-4 antagonizes CD28, diminishing T cell activation and modulating the immunological response. Conversely, the negative regulation of CTLA-4 using monoclonal antibodies (mAbs), particularly ipilimumab, may stimulate T-cell responses against ovarian cancer antigens. We elucidate the mechanisms responsible for immunological suppression: T cell exhaustion and senescence in ovarian cancer. We also provide a synopsis of using CTLA-4 monoclonal antibodies in ovarian cancer alone or conjunction with other modalities (eg, chemotherapy). We finally delineate the challenges associated with responding to immunotherapy in ovarian cancer.
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