Seminars In Oncology[JOURNAL]
Sun
200 papers
Hexokinases in gastrointestinal cancers: From molecular insights to therapeutic opportunities.
Liang G, Ma Y, Deng P … +6 more , Li S, He C, He H, Liu H, Fan Y, Li Z
Semin Oncol · 2025 Aug · PMID 40472682 · Publisher ↗
Hexokinases (HKs) catalyze the first step in glycolysis by transferring a phosphate group to glucose to produce glucose-6-phosphate (G6P); dysregulation of HKs is a feature that leads to altered metabolism within gastroi...
Hexokinases (HKs) catalyze the first step in glycolysis by transferring a phosphate group to glucose to produce glucose-6-phosphate (G6P); dysregulation of HKs is a feature that leads to altered metabolism within gastrointestinal (GI) cancers-namely, gastric, colorectal, esophageal, and pancreatic cancer. Of note, HKs have been found to exert non-canonical roles beyond metabolism, particularly in regulating cell death pathways such as autophagy and apoptosis in these cancers. In this sense, HK2 promotes hepatocellular carcinoma (HCC) from apoptosis inhibition through the suppression of mitochondrial permeability transition pore formation by interaction with voltage-dependent anion channel (VDAC). Moreover, HK2 expression in HCC tumors decreases immune responsiveness and sensitivity to natural killer (NK) cytotoxicity, thus favoring immune escape. HK2 and co-expressed genes participate in esophageal cancer (ESCA) microenvironment immune response, especially in B cells, CD4 T cells, and macrophages. Most importantly, 3-BP, an HK-2 inhibitor, induces endoplasmic reticulum (ER) stress and disruption of the ER function by the accumulation of free radicals or reactive oxygen species (ROS) and the protein misfolding, thereby causing apoptosis in human HCC. Of note, it has been found that interaction of HK domain containing protein-1 (HKDC1) with ACTA2 (actin alpha 2) is required for the association of signal transducer and activator of transcription 1 (STAT1) with interferon-gamma receptor (IFNG-R) on the plasma membrane, STAT1-phosphorylation, and thus programmed cell death ligand 1 (PD-L1) expression upon stimulation with IFNγ in HCC. This review summarizes the mechanistic involvement of HKs in glycolytic reprogramming, apoptotic resistance, autophagy, immune evasion, metastasis, and drug resistance in GI cancers and the potential of HKs as diagnostic and therapeutic targets.
The Crucial Nexus: Unveiling the Role of Collagen in Cancer Progression.
Reeva H, Mahesh G, Manjunath U … +2 more , Selvamurugan N, MohanKumar D
Semin Oncol · 2025 Jun · PMID 40446484 · Publisher ↗
The complex interplay between collagen and cancer cells within the tumor microenvironment (TME) highlights the pivotal role of collagens in cancer progression, prognosis and therapy resistance. As a critical structural p...
The complex interplay between collagen and cancer cells within the tumor microenvironment (TME) highlights the pivotal role of collagens in cancer progression, prognosis and therapy resistance. As a critical structural protein of the extracellular matrix (ECM), collagen not only maintains tissue architecture but also regulates key physiological functions through complex biosynthetic pathways. Deregulation in collagen biosynthesis, characterized by abnormal transcription, post-translational modifications, and deposition, contributes to ECM remodeling and tumor progression. This review explores the involvement of diverse collagen family members in cancer progression across multiple cancer types. Several collagen isoforms have emerged as key players in cancer progression, influencing tumor behavior and act as potential biomarkers for prognosis. Furthermore, circulating collagen fragments in blood present promising avenues for non-invasive cancer diagnosis and disease monitoring. Tumor collagen remodeling alters ECM architecture, impacting tumor-stromal interactions and fostering a microenvironment conducive to favour invasion and metastasis. Mechanistic insights reveal that collagen-induced signalling pathways are the major drivers of stemness, drug resistance, EMT, metastasis, angiogenesis and immune evasion, which collectively shape tumor cell behavior and immune infiltration dynamics. Further, targeting tumor collagen appear to be a viable and robust strategy to treat aggressive desmoplastic and metastatic cancers.
Mechanistic role of FTO in cancer pathogenesis, immune evasion, chemotherapy resistance, and immunotherapy response.
Badraldin SQ, Alfarttoosi KH, Sameer HN … +8 more , Bishoyi AK, Ganesan S, Shankhyan A, Ray S, Nathiya D, Yaseen A, Athab ZH, Adil M
Semin Oncol · 2025 Jun · PMID 40446483 · Publisher ↗
Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) RNA demethylase, plays a key role in cancer biology by regulating mRNA modifications. Its deregulation affects tumor cell proliferation, metastas...
Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) RNA demethylase, plays a key role in cancer biology by regulating mRNA modifications. Its deregulation affects tumor cell proliferation, metastasis, immune evasion, and therapeutic resistance. By removing m6A methylation marks, FTO can alter the stability and translation of key oncogenes and tumor suppressor genes. These modifications directly influence essential cellular pathways involved in cancer progression, such as the phosphatidylinositol 3-kinases/ protein kinase B (PI3K/AKT), Wnt/β-catenin, and mammalian target of rapamycin (mTOR) signaling pathways. This review explores the mechanistic roles of FTO in cancer pathogenesis, focusing on its dual impact on immune regulation and chemotherapy response. In terms of immunity, FTO has been shown to promote immune evasion by modulating the expression of immune checkpoints and influencing the tumor microenvironment. Additionally, FTO's influence on autophagy, glycolysis, and apoptosis resistance further complicates the effectiveness of chemotherapy treatments. By discussing the molecular details of how FTO regulates these processes, we provide insights into how FTO could serve as a promising therapeutic target to overcome cancer-related challenges, including immune resistance and chemotherapy failure. Finally, we evaluate current and emerging strategies for targeting FTO in cancer therapy, highlighting its potential to enhance immunotherapy and chemotherapy outcomes.
Explainable machine learning and feature interpretation to predict survival outcomes in the treatment of lung cancer.
Tegaw EM, Asfaw BB
Semin Oncol · 2025 Jun · PMID 40414043 · Publisher ↗
The treatment outcomes of lung cancer are highly variable, and machine learning (ML) models provide valuable insights into how clinical and biochemical factors influence survival across different treatments. This study w...
The treatment outcomes of lung cancer are highly variable, and machine learning (ML) models provide valuable insights into how clinical and biochemical factors influence survival across different treatments. This study will investigate the survival of patients after four major treatments for lung cancer by interpreting the impact of biomarkers on survival using SHapley Additive exPlanations (SHAP). We analyzed 23,658 lung cancer patient records derived from a Kaggle dataset. Using the most relevant clinical and biochemical variables, ML models were employed to study survival outcomes for different treatments. SHAP analysis revealed major survival predictors in each treatment. Survival outcomes are visualized as f(x) (predicted survival) and E[f(x)] (baseline expectation) in SHAP waterfall plots. The most performed model is Gradient Boosting with an accuracy of 88.99%, precision of 89.06%, recall of 88.99%, F1-score of 88.91%, and Receiver Operating Characteristic Curve (AUC-ROC) score of 0.9332. Chemotherapy treatment was positive for survival, the key for survival was phosphorus levels (+0.05), low Alanine Aminotransferase levels (+0.04) and low glucose levels (+0.04). Targeted therapy and radiation had worse survival, while surgery was favorable, especially in cases with high white blood cell and Lactate Dehydrogenase (LDH) levels. SHAP-based ML analysis aptly underlines how clinical and biochemical factors influence the survival rate. It indicates that ML-driven interpretability might drive personalized treatment approaches in lung cancer.
Divergent functions of TLRs in gastrointestinal (GI) cancer: Overview of their diagnostic, prognostic and therapeutic value.
Hsu CY, Jasim SA, Rasool KH … +7 more , H M, Kaur J, Jabir MS, Alhajlah S, Kumar A, Jawad SF, Husseen B
Semin Oncol · 2025 Jun · PMID 40347779 · Publisher ↗
The relationship between the innate immune signal and the start of the adaptive immune response is the central idea of this theory. By controlling the inflammatory and tissue-repair reactions to damage, the Toll-like rec...
The relationship between the innate immune signal and the start of the adaptive immune response is the central idea of this theory. By controlling the inflammatory and tissue-repair reactions to damage, the Toll-like receptors (TLRs), as a family of PRRs, have attracted increasing attention for its function in protecting the host against infection and preserving tissue homeostasis. Microbial infection, damage, inflammation, and tissue healing have all been linked to the development of malignancies, especially gastrointestinal (GI) cancers. Recently, increased studies on TLR recognition and binding, as well as their ligands, have significantly advanced our knowledge of the various TLR signaling pathways and offered therapy options for GI malignancies. Upon activation by pathogen-associated or damage-associated molecular patterns (DAMPs and PAMPs), TLRs trigger key pathways like NF-κB, MAPK, and IRF. NF-κB activation promotes inflammation, cell survival, and proliferation, often contributing to tumor growth, metastasis, and therapy resistance. MAPK pathways similarly drive uncontrolled cell growth and invasion, while IRF pathways modulate interferon production, yielding both anti-tumor and protumor effects. The resulting chronic inflammatory environment within tumors can foster progression, yet TLR activation can also stimulate beneficial anti-tumor immune responses. However, the functions of TLR expression in GI cancers and their diagnostic and prognostic along with therapeutic value have not yet entirely been elucidated. Understanding how TLR activation contributes to anti-cancer immunity against GI malignancies may hasten immunotherapy developments and increase patient survival.
Advancements and implications of artificial intelligence for early detection, diagnosis and tailored treatment of cancer.
Chadha S, Mukherjee S, Sanyal S
Semin Oncol · 2025 Jun · PMID 40345002 · Publisher ↗
The complexity and heterogeneity of cancer makes early detection and effective treatment crucial to enhance patient survival and quality of life. The intrinsic creative ability of artificial intelligence (AI) offers impr...
The complexity and heterogeneity of cancer makes early detection and effective treatment crucial to enhance patient survival and quality of life. The intrinsic creative ability of artificial intelligence (AI) offers improvements in patient screening, diagnosis, and individualized care. Advanced technologies, like computer vision, machine learning, deep learning, and natural language processing, can analyze large datasets and identify patterns that permit early cancer detection, diagnosis, management and incorporation of conclusive treatment plans, ensuring improved quality of life for patients by personalizing care and minimizing unnecessary interventions. Genomics, transcriptomics and proteomics data can be combined with AI algorithms to unveil an extensive overview of cancer biology, assisting in its detailed understanding and will help in identifying new drug targets and developing effective therapies. This can also help to identify personalized molecular signatures which can facilitate tailored interventions addressing the unique aspects of each patient. AI-driven transcriptomics, proteomics, and genomes represents a revolutionary strategy to improve patient outcome by offering precise diagnosis and tailored therapy. The inclusion of AI in oncology may boost efficiency, reduce errors, and save costs, but it cannot take the role of medical professionals. While clinicians and doctors have the final say in all matters, it might serve as their faithful assistant.
The dual effect of interferon-γ in acute myeloid leukemia: A narrative review.
Angelo AA, Adane G, Berta DM … +4 more , Elias Chane, Cherie N, Tamir M, Teketelew BB
Semin Oncol · 2025 Jun · PMID 40328106 · Publisher ↗
Acute myeloid leukemia (AML) is a hematological malignancy representing a very rapid, uncontrolled growth of myeloid precursors in the BM and peripheral circulation. Studies on AML have highlighted the crucial role of IF...
Acute myeloid leukemia (AML) is a hematological malignancy representing a very rapid, uncontrolled growth of myeloid precursors in the BM and peripheral circulation. Studies on AML have highlighted the crucial role of IFN-γ therapy in immune surveillance, both promotive and inhibitory effects on leukemic cells, and regulation of the tumor microenvironment. However, there is a need for a comprehensive understanding of the dual effects of IFN-γ in AML. Thus, this review aimed to assess the dual effects of IFN-γ in AML. Literature searches were conducted in Pub Med, Google Scholar, and direct Google Search. The data was presented in tables and figures, with findings summarized through a narrative synthesis. Depending on the circumstances and stage of the disease IFN-γ shows two different activities in AML patients. First, IFN-γ enhances NK cells and CD8T lymphocyte functions, which collectively evoke antileukemic immunity. Another promising effect of IFN-γ includes the differentiation of myeloid cells, thereby possibly reducing the severity of leukemia. However, prolonged exposure to IFN-γ can activate Treg cells and inhibitory immunological checkpoints, which can help leukemia evade immune surveillance and encounter an immunosuppressive environment. Our review highlights IFN-γ's critical role in the complex interplay between the immune system and AML pathogenesis. Its dual role in both inhibiting and promoting leukemic processes has been highlighted. However, future pre-clinical and clinical studies should focus on the specific mechanisms by which IFN-γ impacts AML progression and treatment outcomes, with the goal of achieving curative results for patients.
Epidemiology and prevention of gastric cancer: A comprehensive review.
Pradhan SP, Gadnayak A, Pradhan SK … +1 more , Epari V
Semin Oncol · 2025 Jun · PMID 40305929 · Publisher ↗
Gastric cancer is the third most deadly cancer worldwide. Helicobacter pylori (H. pylori) infection and specific diets are key risk factors for this illness, which is more frequent in various nations. Nearly half of the...
Gastric cancer is the third most deadly cancer worldwide. Helicobacter pylori (H. pylori) infection and specific diets are key risk factors for this illness, which is more frequent in various nations. Nearly half of the world's population, 4.4 billion, had H. pylori in 2015. East has a higher incidence rate than West. GC may spread to the liver, lungs, and bones. The majority of cases are adenocarcinomas (90%). In 2022, stomach cancer caused 968,784 new cases and 660,175 deaths worldwide. GC accounts for 7% of cancer diagnoses and 9% of deaths. The high death rate of gastric cancer highlights the need for preventative methods to improve prognosis. Early identification via biomarker screening, especially in high-risk groups, may improve outcomes and treatments.
Advances and challenges in cancer immunotherapy: Strategies for personalized treatment.
Azmal M, Miah MM, Prima FS … +3 more , Paul JK, Haque ASNB, Ghosh A
Semin Oncol · 2025 Jun · PMID 40305928 · Publisher ↗
Cancer immunotherapy has transformed oncology by harnessing the immune system to specifically target cancer cells, offering reduced systemic toxicity compared to traditional therapies. This review highlights key strategi...
Cancer immunotherapy has transformed oncology by harnessing the immune system to specifically target cancer cells, offering reduced systemic toxicity compared to traditional therapies. This review highlights key strategies, including adoptive cell transfer (ACT), immune checkpoint inhibitors, oncolytic viral (OV) therapy, monoclonal antibodies (mAbs), and mRNA-based vaccines. ACT reinfuses enhanced immune cells like tumor-infiltrating lymphocytes (TILs) to combat refractory cancers, while checkpoint inhibitors (eg, PD-1 and CTLA-4 blockers) restore T-cell activity. OV therapy uses engineered viruses (eg, T-VEC) to selectively lyse cancer cells, and advanced mAbs improve targeting precision. mRNA vaccines introduce tumor-specific antigens to trigger robust immune responses. Despite significant progress, challenges like immune-related side effects, high costs, and immunosuppressive tumor microenvironments persist. This review underscores the need for combination strategies and precision medicine to overcome these barriers and maximize the potential of immunotherapy in personalized cancer treatment.
Exploring the clinical trials, regulatory insights, and challenges of PROTACs in oncology.
M S, Joga R, Gandhi K … +3 more , Yerram S, Raghuvanshi RS, Srivastava S
Semin Oncol · 2025 Apr · PMID 40253775 · Publisher ↗
While various targeted therapies exist for cancer, resistance mechanisms remain a significant challenge. Recent advancements in cancer treatment have led to the emergence of proteolysis-targeting chimeras (PROTACs), a pr...
While various targeted therapies exist for cancer, resistance mechanisms remain a significant challenge. Recent advancements in cancer treatment have led to the emergence of proteolysis-targeting chimeras (PROTACs), a promising technology utilizing hetero-bifunctional molecules to target and degrade proteins implicated in cancer progression through the ubiquitin-proteasome system (UPS). PROTACs offer a novel approach, with recent studies and clinical trials demonstrating promising outcomes in degrading endogenous proteins linked to cancer. This work explores classification, regulatory approvals, and ongoing clinical trials of PROTAC technology in cancer management. It emphasizes the importance of regulatory compliance to expedite approvals from relevant authorities. It also highlights challenges and opportunities associated with their implementation. Despite these preliminary efforts, PROTACs show immense potential in effectively addressing cancer. Their ability to target specific proteins for degradation represents a significant advancement in cancer therapeutics, offering new hope for improved outcomes in patient care.
Integrated analysis of scRNA-seq and bulk RNA-seq data identifies BHLHE40 as a key gene in pancreatic cancer progression and gemcitabine resistance.
Wu Y, Zhang C, Huang J … +8 more , Chen Q, Zhang Y, Liu F, Xu D, Jiang K, Shi R, Chen M, Yuan H
Semin Oncol · 2025 Apr · PMID 40250076 · Publisher ↗
OBJECTIVE: Pancreatic cancer is characterized by its high mortality rate and short survival periods, and novel therapeutic targets and tailor personalized strategies are urgently needed. In this study, we aim to investig...
OBJECTIVE: Pancreatic cancer is characterized by its high mortality rate and short survival periods, and novel therapeutic targets and tailor personalized strategies are urgently needed. In this study, we aim to investigate the molecular mechanisms underlying pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance, with a focus on identifying novel therapeutic targets. METHODS: Multiomics approaches were integrated to identify novel actionable targets for PDAC. Public datasets such as TCGA and GEO were utilized to investigate the relationship between gene expression and clinical outcomes. Functional enrichment, cell-cell communication, and metabolic pathway analyses were performed to reveal PDAC heterogeneity and therapeutic resistance mechanisms. RESULTS: BHLHE40 was identified as a hub gene linked to high-CNV PDAC cells, Gemcitabine resistance, and poor prognosis in PDAC. High BHLHE40 expression is significantly correlated with immunosuppressive tumor microenvironment (TME) features such as reduced CD8+ T infiltration, TCR richness, and lower tumor mutational burden (TMB). ChIP-seq data analysis confirmed BHLHE40 could directly bind to the SAT1 promoter, establishing a transcriptional axis promoting chemoresistance. Single-cell RNA-seq analysis further revealed that the BHLHE40+/SAT1+ subpopulation cells are resistant to Gemcitabine in PDAC. CONCLUSIONS: BHLHE40 is significantly correlated with PDAC malignancy and chemoresistance via SAT1 regulation and immune evasion. Targeting BHLHE40 may sensitize PDACs to Gemcitabine and facilitate personalized treatment for BHLHE40+ PDAC patients.
The interest of therapeutic and pharmacological drug monitoring of methotrexate: A systematic review.
Chellal W, Metarfi Y, Ben Khadda Z … +3 more , Hoummani H, Berrady R, Achour S
Semin Oncol · 2025 Apr · PMID 40245550 · Publisher ↗
Methotrexate (MTX) is largely prescribed for cancers, particularly hematological malignancies. To reduce its toxicity, therapeutic drug monitoring (TDM) is highly recommended. This review aimed to assess knowledge on met...
Methotrexate (MTX) is largely prescribed for cancers, particularly hematological malignancies. To reduce its toxicity, therapeutic drug monitoring (TDM) is highly recommended. This review aimed to assess knowledge on methotrexate monitoring and compare strategies for managing its toxicities. We searched several databases for articles that met the selection criteria. All articles were screened and data on analytical methods, results, and toxicities were extracted. Thirty articles were included in this review, consisting mainly of single-center studies. MTX monitoring studies have been conducted in various countries. Patient demographics covered children and adults, with one study focusing on elderly patients. MTX doses varied primarily between high-dose regimens. Sample collection times were varied. Various techniques were used to quantify MTX levels. This review highlights the diversity of study designs, patient populations, dosing regimens, and analytical techniques, emphasizing the need for standardized protocols and further research to optimize MTX treatment, ensuring both efficacy and safety.
Liquid biopsy: An innovative tool in oncology. Where do we stand?
Martella S, Wekking D, Lai E … +9 more , Lambertini M, Pettinato A, Parrino A, Semonella F, Sanna G, Maccioni A, Scartozzi M, Addeo A, Solinas C
Semin Oncol · 2025 Apr · PMID 40233447 · Publisher ↗
The Liquid Biopsy (LB) represents an ideal surrogate of tumor Tissue Biopsy (TB) when the aim is to obtain useful information on patient prognosis and personalized therapy. This technique renders it possible to isolate c...
The Liquid Biopsy (LB) represents an ideal surrogate of tumor Tissue Biopsy (TB) when the aim is to obtain useful information on patient prognosis and personalized therapy. This technique renders it possible to isolate circulating tumor cells, circulating tumor DNA and other molecules from biological fluids. The most commonly used fluid for liquid biopsy is blood, but depending on the case it could be necessary to isolate the tumor components from other biological fluids such as urine, pleural effusion, cerebrospinal fluid, and others. The main advantages of liquid biopsy are the minimally invasive nature of the procedure and the possibility of analyzing all tumor clones. Limitations include difficulties in the isolation of tumor components and the requirement for highly sensitive analysis methods to avoid the risk of technical artifacts. In our review we will focus on describing circulating tumor biomarkers to illustrate the variety of information that can be obtained from biological fluids, particularly blood. We will then discuss the advanced biotechnological techniques suitable for the identification and analysis of Circulating Tumor DNA (ctDNA), examining both the potential and limitations of analytical methods and the clinical applicability of liquid biopsy for cancer diagnosis, monitoring, and therapeutic prediction. Additionally, we will explore strategies to enhance this valuable alternative to the more invasive tissue biopsy, with a dedicated focus on ongoing clinical studies, currently approved tests, and guideline recommendations.
Circular RNAs: Emerging regulators of signaling pathways in epithelial-mesenchymal transition and angiogenesis during breast cancer progression.
Sasi N, Preetha D, Iyyappan S … +1 more , Selvamurugan N
Semin Oncol · 2025 Apr · PMID 40220369 · Publisher ↗
Circular RNAs (circRNAs) have emerged as important regulators of gene expression and cellular activities, and abnormalities in circRNAs in breast cancer have been linked to important biological processes like epithelial-...
Circular RNAs (circRNAs) have emerged as important regulators of gene expression and cellular activities, and abnormalities in circRNAs in breast cancer have been linked to important biological processes like epithelial-mesenchymal transition (EMT) and angiogenesis, both essential for tumor metastasis. EMT facilitates the transition of epithelial cancer cells into a mesenchymal phenotype, enhancing their invasive and migratory capabilities, while angiogenesis promotes tumor progression by forming new blood vessels. CircRNAs also interact with microRNAs to regulate signaling pathways such as TGF-β, Wnt/-catenin, and VEGF. Besides EMT and angiogenesis, studies have identified that circRNAs affect metabolic reprogramming, chemoresistance, tumor microenvironment remodeling, and immunological evasion. Thus, circRNAs play a multifaceted role in the development of breast cancer. They hold potential as non-invasive biomarkers and therapeutic targets due to their high stability, resistance to exonuclease degradation, abundance in body fluids, and diverse expression patterns across different tissues. This review summarizes and critically assesses existing understanding of the functional roles and molecular processes of circRNAs in controlling EMT and angiogenesis during breast cancer progression.
High tumor mutation burden mitigates the negative impact of chemotherapy history on immune checkpoint blockade therapy.
Zheng M
Semin Oncol · 2025 Apr · PMID 40081267 · Publisher ↗
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Immune checkpoint inhibitor (ICI) therapy, particularly with PD-1...
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Immune checkpoint inhibitor (ICI) therapy, particularly with PD-1 inhibitors like nivolumab, has become a critical treatment option for advanced NSCLC. ICI therapy has revolutionized treatment, but prior chemotherapy may diminish ICI treatment efficacy. Tumor mutation burden (TMB) has emerged as a crucial predictor of ICI response, yet its interaction with chemotherapy history in ICI therapy is not fully understood. In this study, I investigate the impact of chemotherapy history on ICI treatment outcomes, focusing on TMB as a potential mitigating factor. Analyzing data from 512 patients with advanced NSCLC treated with PD-1/PD-L1 or CTLA-4 inhibitors, this sudy found that prior chemotherapy significantly reduced objective response rates (ORR) to ICI therapy, particularly in patients with low TMB (<15 mut/Mb). However, in patients with high TMB (≥15 mut/Mb), the negative impact of chemotherapy history on ICI treatment efficacy is minimal, suggesting that high TMB mitigates chemotherapy-induced resistance to ICI therapy. Furthermore, while chemotherapy history is associated with worse overall survival (OS) and progression-free survival (PFS) following ICI therapy in low-TMB patients, no such association is observed in high-TMB patients. These findings highlight the importance of TMB as a predictive biomarker, emphasizing the need for optimal treatment sequencing and personalized therapeutic strategies to overcome chemotherapy-induced immune resistance and maximize ICI treatment efficacy. These results suggest that ICI therapy may be more beneficial as a first-line treatment, particularly for patients with low TMB.
Plant polyphenols in gastric cancer: Nature's healing touch.
Niu C, Zhang J, Okolo PI … +1 more , Daglilar E
Semin Oncol · 2025 Apr · PMID 40073717 · Publisher ↗
Globally, gastric cancer ranks as the fifth most common cancer and is the third most common cause of malignancy-associated mortality. Although surgery is the primary treatment option for gastric cancer, adjuvant chemothe...
Globally, gastric cancer ranks as the fifth most common cancer and is the third most common cause of malignancy-associated mortality. Although surgery is the primary treatment option for gastric cancer, adjuvant chemotherapy improves survival in patients following surgery. Proverbially, plant polyphenols have many beneficial health effects, including anticancer properties. Extensive studies have shown that plant polyphenols exhibit potential anticancer effects against gastric cancer in vitro and in vivo, as well as very few human studies. However, this topic has not yet been reviewed. The present review shows that the potential anticancer effect of plant polyphenols on gastric cancer was preliminarily attributed to their antiproliferative, antimetastatic, and antiangiogenic effects and modulations of apoptosis, autophagy, and intracellular reactive oxygen species. Moreover, conventional therapeutics combined with plant polyphenols make gastric cancer cells more sensitive to conventional therapy. We also discuss challenges and opportunities in translating plant polyphenol-based therapy to clinical applications. The content provided in this review is of interest to pharmacologists, ethnobotanists, and oncologists who are involved in phytomedicine.
Fingerprint change as a consequence of anticancer treatments: A systematic integrative review.
Belloni S, Magon A, de Sanctis R … +4 more , Tiberio P, Conte G, Arrigoni C, Caruso R
Semin Oncol · 2025 Feb · PMID 40037149 · Publisher ↗
OBJECTIVE: While it is widely acknowledged that fingerprint recognition has played an essential part in policing and forensic science, little is known about fingerprint alterations in medical science, specifically as a c...
OBJECTIVE: While it is widely acknowledged that fingerprint recognition has played an essential part in policing and forensic science, little is known about fingerprint alterations in medical science, specifically as a consequence of anticancer treatments. Thus, we aimed to analyze the extent of evidence between cancer treatments and fingerprint alterations in adults with cancer. METHODS: A systematic integrative review was conducted according to the PRISMA statement and the Cochrane guidelines for conducting a systematic review. PubMed, CINAHL, Web of Science, and Scopus were searched from the inception between August and November 2024. The quality appraisal was conducted to evaluate the methodological quality of the included articles, selecting the most appropriate tool based on the publication type and study design. RESULTS: Of 176 records, we selected five experimental studies articles and nine case reports publications. A correlation between specific anticancer treatments (capecitabine, taxanes, and tyrosine kinase inhibitors) and fingerprint alterations has been documented in individuals with various cancer diagnoses (mainly advanced breast and colorectal cancers). The majority of articles were of moderate to low quality. CONCLUSIONS: Although fingerprint alteration as a consequence of specific anticancer treatments has been documented, further large and well-designed experimental studies are necessary to quantify the phenomenon burden in relation to specific anticancer regimens and populations. PROSPERO REGISTRATION N: (CRD42024581192).
The critical role of NLRP3 in drug resistance of cancers: Focus on the molecular mechanisms and possible therapeutics.
Kuriakose BB, Zwamel AH, Mutar AA … +7 more , Uthirapathy S, Bishoyi AK, Naidu KS, Hjazi A, Nakash P, Arya R, Almalki SG
Semin Oncol · 2025 Feb · PMID 40037148 · Publisher ↗
Nod-like receptor protein 3 (NLRP3) is a member of the leucine-rich repeat-containing protein (NLR) canonical inflammasome family. It regulates the pathophysiology of cancer by facilitating immune responses and apoptotic...
Nod-like receptor protein 3 (NLRP3) is a member of the leucine-rich repeat-containing protein (NLR) canonical inflammasome family. It regulates the pathophysiology of cancer by facilitating immune responses and apoptotic proteins. Furthermore, it has been observed that chemotherapy activates NLRP3 in human malignancies. The secretion of IL-1β and IL-22 to promote cancer spread may be triggered by NLRP3 activation. Furthermore, earlier studies have exhibited that NLRP3 may cause medication resistance when used in cancer treatments given that cell viability may be regulated by NLRP3 depletion. Additionally, clinical studies have demonstrated correlation between NLRP3 expression, lymphogenesis, and cancer metastasis. Various NLRP3 agonists may cause the EMT process, stimulate IL-1β and Wnt/β-catenin signaling, and alter miRNA function in drug-resistant cells. This review seeks to clarify the possibility involvement of NLRP3-related pathways in the control of cancer cells' resistance to widely used treatment approaches, such as chemotherapy. In the end, an improved perception of the corresponding mechanisms behind NLRP3's tumor-supporting activities will help NLRP3-based treatments advance in the future.
Obesity correlates to the microsatellite instability of endometrial cancer: A retrospective observational study.
Ronsini C, Braca E, Fordellone M … +5 more , Marino FZ, Napolitano S, Raffone A, Cobellis L, De Franciscis P
Semin Oncol · 2025 Feb · PMID 40009888 · Publisher ↗
OBJECTIVE: To investigate the relationship between obesity and Microsatellite Instability (MSI) in endometrial cancer (EC), determine which mismatch repair (MMR) protein loss is influenced by obesity, and assess the corr...
OBJECTIVE: To investigate the relationship between obesity and Microsatellite Instability (MSI) in endometrial cancer (EC), determine which mismatch repair (MMR) protein loss is influenced by obesity, and assess the correlation between BMI and MSI probability. METHODS: This retrospective cohort study included 89 endometrial cancer patients treated at the Gynaecologic oncology unit of the University of Campania "Luigi Vanvitelli" from August 2023 to October 2024, and stratified by BMI: normal weight (n = 26), overweight (n = 31), obese (n = 26), and severely obese (n = 6). Microsatellite instability (MSI) was determined through immunohistochemical assessment of mismatch repair (MMR) protein expression: MLH1, PMS2, MSH2, and MSH6. Tumors were considered MSI if at least one of the four MMR proteins showed loss of expression. Univariate and multivariate logistic regression models were constructed to evaluate the correlation between BMI and MSI RESULTS: 89 patients were enrolled. Obese and severely obese groups showed significantly higher MSI rates (50 % each) compared to normoweight (12 %) and overweight (29 %) groups (P = .013). MLH1 and PMS2 loss of expression were significantly higher in obese and severely obese women (MLH1: P = .003; PMS2: P = .014). Univariate logistic regression showed a significant positive correlation between BMI and MSI (OR 1.02, 95 % CI 1.01-1.04, P = .007). In multivariate analysis, adjusting for grading, stage, histotype, and age, BMI maintained a significant positive correlation with MSI (OR 1.02, 95 % CI 1.01-1.04, P = .048). CONCLUSIONS: This study demonstrates a significant association between obesity and MSI in EC, particularly affecting MLH1 and PMS2 expression. The findings suggest that obesity may contribute to EC development also through MMR deficiency.
The likelihood of being helped or harmed obtained from clinical trial results for cancer therapy: Can it really help?
Bronte G
Semin Oncol · 2025 Feb · PMID 39837750 · Publisher ↗
The majority of cancer clinical trials leading to therapeutic approval focus on outcomes such as objective tumor responses, progression-free survival (PFS), and overall survival (OS). However, it is equally important to...
The majority of cancer clinical trials leading to therapeutic approval focus on outcomes such as objective tumor responses, progression-free survival (PFS), and overall survival (OS). However, it is equally important to assess toxicity, especially when comparing standard therapies with experimental ones. Clinical trials often fail to synthesize the relationship between efficacy and adverse event frequency, partly due to differences in measurement units. To address this, the number needed to treat (NNT) and number needed to harm (NNH) can be used as standardized measures. NNT represents the number of patients required to benefit from a treatment, while NNH indicates the number needed to experience harm. These metrics allow for a more balanced evaluation of therapeutic efficacy and toxicity. By calculating NNT for PFS or OS and NNH for adverse events, we can assess the therapeutic benefit relative to potential harm. The likelihood of being helped or harmed (LHH) combines these metrics into a ratio that expresses the balance between benefit and toxicity. Ideally, LHH values greater than 1 indicate a favorable balance toward efficacy. Though LHH has been applied mainly to psychotropic drugs, it was used in oncology sometimes. For example, studies in advanced non-small cell lung cancer and breast cancer have demonstrated LHH's utility in comparing treatments. Whereas LHH calculation has some limitations, it offers a valuable tool for explaining treatment risks and benefits to patients. It also could guide clinical trial design in cancer therapy.
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