Scimone C, Palumbo L, Borea R
… +10 more, Sarracino C, Tomaiuolo I, Di Giovanni D, Alfano S, Nacchio M, Russo G, Russo A, Pepe F, Troncone G, Malapelle U
INTRODUCTION: In the era of precision medicine, molecular biomarker testing is increasingly becoming the standard of care for Non-Small Cell Lung Cancer (NSCLC) patients. Tissue and liquid biopsy-based Next-Generation Se...INTRODUCTION: In the era of precision medicine, molecular biomarker testing is increasingly becoming the standard of care for Non-Small Cell Lung Cancer (NSCLC) patients. Tissue and liquid biopsy-based Next-Generation Sequencing (NGS) is now highly recommended. AREAS COVERED: Different NGS platforms emerged as a cost-effective strategy to perform a massive and parallel sequencing performing higher technical sensitivity than old generation technologies in detecting low abundant alterations in challenging diagnostic samples. NGS systems can detect single nucleotide variants (SNV), small insertions, and deletions (indels), copy number alterations (CNAs) and structural variants (SVs) or gene fusions across selected druggable genes optimizing clinical administration of NSCLC patients. The diagnostic implementation of the most adequate NGS panel depending on several factors that could impact on the clinical utility of the testing assay. EXPERT OPINION: Promising advanced technologies are emerging as potentially integrative tools in personalized medicine. In this context, multi-omic evaluation including genomic, transcriptomic, fragmentomic and epigenomic signatures are under investigation to significantly modify clinical algorithms of NSCLC patients. On this basis, sequencing strategies may play a pivotal role in the implementation of a new predictive model for cancer diagnosis and prognosis.
OBJECTIVE: To evaluate the cost-effectiveness of toripalimab combined with chemotherapy for the first-line treatment of extensive-stage small cell lung cancer. METHODS: A partitioned survival model was employed with data...OBJECTIVE: To evaluate the cost-effectiveness of toripalimab combined with chemotherapy for the first-line treatment of extensive-stage small cell lung cancer. METHODS: A partitioned survival model was employed with data sourced from the EXTENTORCH clinical trial and related literature. The simulation period was set to 10 years, with a cycle of 3 weeks, and all cost and utility indicators were adjusted using a 5% annual discount rate. Using QALYs as the main evaluation indicator, ICERs were calculated to compare the economic differences between treatment with TC group and PC group. The reliability of the research results was verified through single-factor sensitivity analysis and probabilistic sensitivity analysis. RESULTS: From the base analysis indicate that the ICER for the TC group relative to the PC group is $3,151 per QALY, which is significantly lower than the WTP set at three times the 2024 per capita GDP of China. Sensitivity analysis shows that the discount rate, incidence of hematotoxicity in TC group, number of treatment cycles and other parameters have the greatest impact on ICER. CONCLUSION: At the current willingness-to-pay threshold for Chinese patients, the combination of toripalimab and chemotherapy demonstrates superior cost-effectiveness compared to traditional chemotherapy.
INTRODUCTION: Understanding histological variants is crucial for accurate diagnosis and management of bladder cancer (BC). Most BCs are urothelial carcinomas (UC), which can evolve into aggressive histological variants (...INTRODUCTION: Understanding histological variants is crucial for accurate diagnosis and management of bladder cancer (BC). Most BCs are urothelial carcinomas (UC), which can evolve into aggressive histological variants (HVs) such as micropapillary, plasmacytoid, small-cell carcinoma, and sarcomatoid subtypes. AREAS COVERED: This review will focus on the clinicopathologic characteristics of the most common non-urothelial and other rare variants (signet-ring cell variant, decoy cells, osteoclastic giant cell variant) BCs, to be distinguished from BC variant histology containing a UC component. In addition, we reviewed the effects of understanding HVs in developing therapeutic and diagnostic methods for BC. Our analysis combines evidence from searches in PubMed/NCBI, Google Scholar, ClinicalTrials.gov, and key conference proceedings from 2011 to 2025. EXPERT OPINION: Recognizing and differentiating between various variant histology (VH) subtypes is crucial for tailoring treatment strategies and improving patient outcomes. Discovering and uniform reporting of variant histology in UC is essential. Clinical trials focusing specifically on patients with HVs are needed to evaluate the impact of new treatment modalities and optimize management strategies. More clinical studies with specific guidelines and goals, along with research, patient records, databases, and tissue banks, are needed to improve treatment plans and identify markers for patients with urinary tract cancer.
BACKGROUND: Breast cancer is a prevalent malignancy, and statins are commonly used in the treatment of hyperlipidemia. However, the association between the use of statins and the risk of breast cancer is unclear. The aim...BACKGROUND: Breast cancer is a prevalent malignancy, and statins are commonly used in the treatment of hyperlipidemia. However, the association between the use of statins and the risk of breast cancer is unclear. The aim of our study was to explore the relationship between statins and breast cancer risk by combining data analysis from the NHANES (National Health and Nutrition Examination Survey) and a Mendelian randomization (MR) study. RESEARCH DESIGN AND METHODS: We collected and compiled data from the NHANES between 2003 and 2016. Logistic regression models were used to evaluate the associations between statin use and the risk of breast cancer. To further validate our findings, we selected two sets of instrumental variables and conducted a MR study. Additionally, we evaluated the robustness and reliability of the MR results through sensitivity analyses. RESULTS: Based on the results of multivariate logistic regression analysis, statins may be a potential protective factor against breast cancer. For the MR analyses, inverse-variance weighted (IVW) analysis also revealed an association between exposure to statin-targeted inhibition and the risk of breast cancer. CONCLUSION: The administration of statins contributes to reduce the risk of breast cancer, which may open up new perspectives on breast cancer prevention.
BACKGROUND: Glycosylphosphatidylinositol-anchored proteins (GPI-APs) contribute to cancer progression, with their glycolipid modification mediated by glycosylphosphatidylinositol transamidase (GPIT). Phosphatidylinositol...BACKGROUND: Glycosylphosphatidylinositol-anchored proteins (GPI-APs) contribute to cancer progression, with their glycolipid modification mediated by glycosylphosphatidylinositol transamidase (GPIT). Phosphatidylinositol glycan anchor biosynthesis class T (PIGT), a key GPIT subunit, influences GPI-APs biosynthesis and tumor biology. This study investigates PIGT expression in hepatocellular carcinoma (HCC) and its regulatory mechanisms. METHODS: HCC genome sequencing and The Cancer Genome Atlas (TCGA) database were analyzed to compare PIGT expression between tumor and adjacent normal tissues. PIGT knockdown and overexpression cell lines examined its influence on HCC cell proliferation, migration, and invasion. Gene Set Enrichment Analysis (GSEA) identified downstream pathways, and Japan Australia Singapore Profiling Array Repository (JASPAR) predicted upstream transcriptional regulators, which were validated by in vivo tumor models. RESULTS: PIGT was upregulated in HCC, enhancing tumor cell aggressiveness. GSEA implicated oncogenic pathways, and JASPAR identified homeobox B7 (HOXB7) as key transcriptional regulator. Animal models validated HOXB7-induced PIGT upregulation and its role in HCC progression. CONCLUSIONS: PIGT promotes the HCC malignancy via the Wnt/β-catenin pathway, with HOXB7 as its upstream regulator.
INTRODUCTION: Allogeneic chimeric antigen receptor (CAR) T-cell therapy is a promising yet underexplored treatment for clear cell renal cell carcinoma (ccRCC), potentially more effective than existing treatment options....INTRODUCTION: Allogeneic chimeric antigen receptor (CAR) T-cell therapy is a promising yet underexplored treatment for clear cell renal cell carcinoma (ccRCC), potentially more effective than existing treatment options. This review compares several ongoing preclinical and clinical trials using CAR T-cell therapy. AREAS COVERED: This review discusses the development of CAR T-cell therapy in ccRCC, covering four significant themes: (1) optimizing therapeutic efficacy through combination strategies, (2) the translation pathway from preclinical development to clinical application, (3) safety and toxicity management, and (4) immune response modulation in the tumor microenvironment. Finally, this review highlights opportunities to overcome current limitations and guide future therapeutic approaches. We conducted a structured review of existing research using the PubMed and Google Scholar databases from the past 5 years, compiled relevant studies on CAR T-cell therapies for ccRCC, and categorized them into four key themes, which were then cross-analyzed to identify trends, challenges, and emerging limitations. EXPERT OPINION: Development of universal CAR T-cells may be more affordable, more accessible, and easier to administer in less time with fewer mechanical failures than autologous CAR T-cell therapy. Some challenges persist, including patient toxicities, depletion of CAR T-cells in vivo, and an immunosuppressive tumor microenvironment.
INTRODUCTION: Myelodysplastic syndromes/neoplasms (MDS) are a heterogenous group of myeloid cancers that impose a substantial negative impact on patient health-related quality of life. As MDS predominately affects older...INTRODUCTION: Myelodysplastic syndromes/neoplasms (MDS) are a heterogenous group of myeloid cancers that impose a substantial negative impact on patient health-related quality of life. As MDS predominately affects older individuals, who are especially susceptible to the debilitating nature of the disease and its burdensome symptoms, treatment decisions should consider therapeutic value from multiple perspectives to balance clinical efficacy with patient-centered outcomes. This comprehensive approach is known as relative medical value. AREAS COVERED: Although improved outcomes have been observed with hypomethylating agents (HMAs) in patients with higher-risk MDS, parenteral administration of HMA requires frequent infusion clinic visits and is associated with substantial time burden, especially in older patients, impacting treatment persistence. Suboptimal use of HMAs in MDS may lead to poorer outcomes and higher healthcare costs, underscoring the need for patient-centered treatment options that improve persistence. EXPERT OPINION: Oral decitabine and cedazuridine (DEC-C) is an approved treatment for higher-risk MDS and may reduce patient burden associated with parenteral HMA therapy. Oral DEC-C has the potential to improve treatment persistence and clinical outcomes and reduce healthcare resource utilization and costs. This review integrates the available clinical, patient-centered, and economic evidence on the relative medical value of oral DEC-C treatment for MDS.
INTRODUCTION: Chromatin regulators (CRs) are critical in cancer development, yet their prognostic value in lung squamous cell carcinoma (LUSC) remains unclear. This study aimed to develop a CR-based prognostic model and...INTRODUCTION: Chromatin regulators (CRs) are critical in cancer development, yet their prognostic value in lung squamous cell carcinoma (LUSC) remains unclear. This study aimed to develop a CR-based prognostic model and explore the role of APOBEC1 in LUSC progression. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. Gene Ontology and KEGG pathway enrichment were performed. Prognostic CRs were identified using univariate Cox and Lasso analyses. Drug sensitivity was assessed via the Drug Signatures Database. Key CRs were validated by PCR. APOBEC1 expression and prognosis were evaluated through pan-cancer analysis and experimentally validated in LUSC cell lines using colony formation, CCK-8, wound healing, and transwell assays. RESULTS: An eight-gene CR-based signature was established, achieving 5-year AUCs of 0.87, 0.92, and 0.73 in the TCGA training, validation, and GEO datasets, respectively. High-risk patients showed enrichment in cancer-related pathways, greater immune infiltration, and elevated immune checkpoint expression. They were also more sensitive to Dasatinib, Bexarotene, and Bicalutamide. APOBEC1 was overexpressed across multiple cancer types and promoted proliferation and migration in LUSC cell lines. CONCLUSIONS: This study presents a robust CR-based survival model and highlights APOBEC1 as a potential therapeutic target in LUSC.
INTRODUCTION: Urothelial carcinoma (UC) is marked by significant molecular heterogeneity and this complexity challenges precision medicine. Recent advances have improved biomarker development for UC diagnosis, prognosis...INTRODUCTION: Urothelial carcinoma (UC) is marked by significant molecular heterogeneity and this complexity challenges precision medicine. Recent advances have improved biomarker development for UC diagnosis, prognosis and treatment. AREAS COVERED: This review discusses established and emerging biomarkers in UC, including FGFR3 and HER2 alterations, PD-L1 expression and circulating tumor DNA (ctDNA). It also summarizes novel biomarkers such as Nectin-4, TROP-2, HER3, tumor mutational burden (TMB), and interferon-gamma signatures. The expanding role of artificial intelligence in biomarker discovery and interpretation is also addressed. Current literature was reviewed by a systematic search using PubMed, focusing on high-impact clinical trials, guidelines and recent reviews published up to May 2025. EXPERT OPINION: Despite advances, clinical implementation of biomarkers in UC is limited by methodological inconsistencies and lack of standardization. Robust clinical trials and multi-modal approaches, including liquid biopsy, tissue analysis, and AI-driven tools, will be essential to advance precision oncology in UC.
INTRODUCTION: In polymetastatic cancer, radiotherapy (RT) serves as a palliative and symptom-directed approach. Based on modern RT, ablative irradiation has acquired a central role as a metastasis-directed therapy (MDT)....INTRODUCTION: In polymetastatic cancer, radiotherapy (RT) serves as a palliative and symptom-directed approach. Based on modern RT, ablative irradiation has acquired a central role as a metastasis-directed therapy (MDT). MDT is under investigation as a treatment option in patients with widespread metastatic disease. AREAS COVERED: We aimed to describe the emerging field of radiotherapy-based MDT in polymetastatic disease. EXPERT OPINION: New innovative approaches in radiation oncology allow for the precise and safe delivery of ablative doses to multiple disease sites throughout the body in the same treatment session and the tracking of tumors in real time without interruptions during systemic therapy. This treatment strategy could work synergistically with systemic therapy in two ways: [a] ablating high-risk or symptomatic metastases in polymetastatic patients may prevent further disease spread and reduce the overall tumor burden, even while systemic therapy continues to manage micrometastatic disease elsewhere; [b] delivering high doses of radiation to the tumor site leads to microenvironment modifications, inducing immunogenic cell death, releasing tumor antigens, and enhancing immune surveillance and systemic therapy efficacy. Several clinical trials are ongoing to improve tailored treatment strategies in the polymetastatic setting, which is one of the goals of precision medicine.
INTRODUCTION: Radical cystectomy (RC) remains the gold standard surgical treatment for muscle-invasive bladder cancer (MIBC). It is a technically complex procedure with considerable short- and long-term morbidity, even i...INTRODUCTION: Radical cystectomy (RC) remains the gold standard surgical treatment for muscle-invasive bladder cancer (MIBC). It is a technically complex procedure with considerable short- and long-term morbidity, even in experienced hands. AREAS COVERED: This review highlights recent advances in the multidisciplinary management of MIBC across the pre-, peri-, and post-operative phases. Improvements in surgical technique, peri-operative care pathways, and systemic therapies - including immunotherapy - have transformed outcomes. A targeted literature search was conducted using PubMed, Scopus, and Web of Science for English-language articles from 2015-2024, focusing on prospective studies from seminal clinical trials. Salient strategies were selected for inclusion based on clinical relevance and impact on patient outcomes. EXPERT OPINION: Optimizing outcomes for patients undergoing RC requires an evidence-based, patient-centered approach. The addition of immunotherapy in the peri-operative setting has changed the standard of care. In the future, peri-operative treatment decisions may be guided by biomarkers such as circulating tumor DNA. Additionally, optimizing patient comorbidities, delivering individualized patient education, and adhering to enhanced recovery protocols remain essential to optimizing patient outcomes.
INTRODUCTION: Despite strong evidence supporting its effectiveness, single, immediate instillation of intravesical chemotherapy (SI-IVC) following transurethral resection of bladder tumor (TURBT) remains vastly underutil...INTRODUCTION: Despite strong evidence supporting its effectiveness, single, immediate instillation of intravesical chemotherapy (SI-IVC) following transurethral resection of bladder tumor (TURBT) remains vastly underutilized in managing low- and intermediate-risk non - non-muscle-invasive bladder cancer (NMIBC). This review addresses the gap between evidence and practice in adopting this cost-effective, recurrence-reducing intervention and offers potential solutions through an implementation science approach. AREAS COVERED: We examined the clinical benefits of SI-IVC based on landmark trials and meta-analyses across various agents, including mitomycin and gemcitabine. A targeted literature review was conducted using PubMed and major urology guidelines to identify studies assessing efficacy, utilization rates, and barriers to implementation. Particular focus is given to logistical and systems-based challenges limiting real-world application, including issues with drug availability, perioperative workflow, and post-resection coordination. We also discuss strategies informed by an implementation science framework, including planning and system engagement, executing interventions, and evaluating their impact within hospital systems. EXPERT OPINION: Incorporating SI-IVC into routine practice requires pragmatic, system-level changes that address logistical barriers rather than clinical hesitancy. With institutional support and streamlined protocols, SI-IVC can be more consistently delivered, however, local adaptation and fine-tuning remain essential, as healthcare systems and available personnel vary across institutions.
OBJECTIVES: Maintenance therapy is frequently proposed to patients with unresectable metastatic colorectal cancer (mCRC). However, the optimal regimen has not been defined, and studies have failed to characterize the pat...OBJECTIVES: Maintenance therapy is frequently proposed to patients with unresectable metastatic colorectal cancer (mCRC). However, the optimal regimen has not been defined, and studies have failed to characterize the patients who benefit from the maintenance strategy. RESEARCH DESIGN AND METHODS: A systematic search of studies of maintenance was performed. Prospective studies that evaluated the progression-free survival (PFS) from the start of induction to progression and reported overall survival (OS) were selected. The efficacy of induction + maintenance therapy was assessed by the PFS/OS ratio. Twenty-one baseline variables were extracted and a linear regression was performed, separating cohorts in which maintenance included antiangiogenic agent (AAG)-based or fluoropyrimidine (FP)-based regimen. RESULTS: Twenty-three study cohorts related to 18 trials were selected. Analysis of variables versus PFS/OS ratio showed a significant relationship with sex (23 cohorts; β = -0.0082, p-value = 0.016). In the 19 cohorts that received an AAG-based regimen, a benefit was found for females, patients receiving longer oxaliplatin-based induction chemotherapy, lung metastases, while in the 17 cohorts that received an FP-based treatment only patients without a previous primary tumor resection reported higher PFS/OS. CONCLUSIONS: Despite the heterogeneity of the studies, female sex was associated with a more pronounced effect of maintenance regimens, particularly AAG-based.
Tosoni A, Foschini MP, Pasquini E
… +10 more, D'Angelo E, Di Nunno V, Gatto L, Bartolini S, Aprile M, Argento CM, Margotti M, Dima G, Franceschi E, Brandes AA
INTRODUCTION: Sinonasal tumors are rare and heterogeneous malignancies comprising 3-5% of head and neck cancers, often diagnosed at advanced stages due to nonspecific symptoms and anatomical location. Their proximity to...INTRODUCTION: Sinonasal tumors are rare and heterogeneous malignancies comprising 3-5% of head and neck cancers, often diagnosed at advanced stages due to nonspecific symptoms and anatomical location. Their proximity to critical structures complicates both surgery and radiotherapy. While multimodal treatment is standard, the role of chemotherapy remains unclear. Advances in molecular profiling have revealed alterations with prognostic and therapeutic relevance, highlighting the need for continued research to enhance treatment strategies. This review is based on all available prospective and retrospective studies, case reports, and review articles published up to May 2025 in PubMed. AREAS COVERED: This article gives an overview of the current knowledge, showing the histological diversity of this area. In this context, we analyze the more recent data on different local treatment options: open and endoscopic surgery, photon and particles bean radiotherapy. We also discuss the role and timing of chemotherapy approaches. EXPERT OPINION: Advances in molecular characterization begin to define new pathological entities that will further improve in future years. Although clinical management of these rare diseases has been improved in recent years, ongoing research investigating the role of chemotherapy in these rare entities is of paramount importance to define appropriate and effective treatment regimens.
INTRODUCTION: Retinoblastoma is the most common intraocular malignancy in children. Although survival has improved with multimodal therapy, survivors remain at risk for subsequent malignant neoplasms (SMNs), often due to...INTRODUCTION: Retinoblastoma is the most common intraocular malignancy in children. Although survival has improved with multimodal therapy, survivors remain at risk for subsequent malignant neoplasms (SMNs), often due to prior treatments or genetic predisposition. To identify risk factors associated with SMNs in childhood retinoblastoma survivors. METHODS: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251026103). A comprehensive search was conducted in PubMed, Embase, and Scopus up to January 2025. Observational studies reporting SMNs risk factors were included. Study selection, data extraction, and quality assessment were independently performed by two reviewers. RESULTS: Of 1,640 records, five studies met the inclusion criteria. The main risk factors identified were: radiotherapy, especially linked to bone and soft tissue sarcomas; chemotherapy, notably alkylating agents and anthracyclines; germline RB1 mutations and Li-Fraumeni syndrome; bilateral retinoblastoma; and socioeconomic disparities, with increased SMNs incidence in low- and middle-income countries. One study reported a potential protective role of proton therapy. CONCLUSION: Radiotherapy, chemotherapy, and genetic predisposition are key risk factors for SMNs in retinoblastoma survivors. Standardized prospective studies are needed to guide prevention strategies and survivor care. REGISTRATION: PROSPERO (CRD420251026103).
INTRODUCTION: Mycosis fungoides (MF) and Sézary syndrome (SS) are T cell lymphomas of the skin with prolonged clinical course requiring multiple lines of therapy in a patient's lifetime. The treatment of MF/SS with avail...INTRODUCTION: Mycosis fungoides (MF) and Sézary syndrome (SS) are T cell lymphomas of the skin with prolonged clinical course requiring multiple lines of therapy in a patient's lifetime. The treatment of MF/SS with available agents is complicated by the differential response in skin, lymph nodes, and blood. Advances in understanding the biology of the disease have led to therapies with better efficacy and improvement in quality of life for patients with relapsed and refractory disease. AREAS COVERED: This review will outline clinical data for novel biologics including monoclonal antibodies, small molecule inhibitors, and immunotherapeutic approaches such as CAR-T and bispecific antibodies. EXPERT OPINION: Nonchemotherapy options which avoid generalized immunosuppression are a preferred consideration for patients with MF/SS, given the compromised skin integument of these patients. Targeted therapies including brentuximab vedotin, lacutamab, denileukin diftitox, and mogamulizumab have shown activity in registrational trials. Novel agents which modulate tumor microenvironment and upregulate tumor-specific immune responses have been in clinical trials, including bispecific antibodies recruiting immune effectors, agents eradicating suppressive microenvironments, and engineered T cells targeting tumor epitopes. Checkpoint inhibitors may play a role in MF/SS but their role has not been well defined, and they may induce hyper progression.