Search Results (18,742)

Early cancer detection is critical for improving patient outcomes, yet current diagnostic approaches often fail to identify malignancies when tumor-specific biomarkers are relatively scarce. Emerging CRISPR/Cas-based technologies have revolutionized the ultra-sensitive detection of cancer biomarkers in liquid biopsies, overcoming the inherent limitations of traditional diagnostic approaches such as tissue biopsies and imaging, which frequently fail to detect early-stage malignancies with sufficient sensitivity. This review explores recent advances in CRISPR/Cas diagnostics (CRISPR/Cas-Dx) that employ programmable CRISPR effectors, including Cas9, Cas12, Cas13, and Cas14. In particular, the collateral (trans-) cleavage activities of Cas12, Cas13, and Cas14 enable signal amplification for highly sensitive detection of circulating tumor DNA, microRNAs, exosomes, and other multi-omics biomarkers, often without the need for extensive nucleic acid amplification. Representative CRISPR/Cas-Dx platforms include amplification-coupled assays, amplification-free frameworks, biosensing and multiplexing capabilities, and new digital or droplet-based configurations that include artificial intelligence to improve analytical precision. These technologies demonstrate single-molecule resolution and adaptability for point-of-care testing in malignancies such as non-small cell lung, colorectal, and breast carcinoma. Finally, we outline a clinical translation roadmap encompassing manufacturability, regulatory and standardization requirements, and real-world implementation challenges. This perspective offers a blueprint for CRISPR-powered, ultra-sensitive liquid biopsy diagnostics that can enable population-scale early cancer screening and truly preventive oncology by bridging molecular insights, engineering innovation, and clinical imperatives. Full article

The management of oligometastatic disease has undergone a significant paradigm shift over the past two decades. Once considered uniformly incurable, selected patients with metastatic disease can now achieve prolonged progression-free survival, durable disease control, and, in carefully selected cases, long-term remission or cure through metastasis-directed therapies. Advances in stereotactic ablative radiotherapy (SABR), surgery, systemic therapies, and the emerging concept of Curative Oligometastatic Radiotherapy (CORT) have challenged the traditional distinction between curative and palliative treatment. Concurrent developments in imaging, including PET/CT, prostate-specific membrane antigen (PSMA) PET, whole-body MRI, and MR-guided adaptive radiotherapy (MR-linac), together with evolving biomarker research, are improving disease characterisation, refining patient selection, and treatment personalisation. As survival improves, an increasing number of patients are living with durably controlled metastatic cancer and experience long-term physical, psychological, cognitive, functional, and financial consequences of treatment. Despite these challenges, evidence-based survivorship pathways for patients with oligometastatic disease remain poorly defined. Supportive oncology is becoming an essential component of modern radiation oncology rather than an adjunct to cancer treatment. This emerging discipline focuses on optimising symptom control, minimising toxicity, and delivering structured survivorship care. Rather than being limited to end-of-life care, supportive oncology is embedded throughout the patient journey; from diagnosis and treatment selection to prehabilitation, rehabilitation, patient-reported outcome (PRO) monitoring, surveillance for late effects, multidisciplinary follow-up, and long-term survivorship. This review discusses how advances in precision radiotherapy, molecular imaging, biomarkers, and emerging treatment technologies are reshaping the management of oligometastatic disease while simultaneously creating a growing population of long-term survivors with increasingly complex supportive care needs. It highlights the expanding role of supportive oncology in the care of patients with oligometastatic disease, encompassing multidisciplinary symptom management and argues that improvements in disease control must now be matched by the development of evidence-based multidisciplinary survivorship pathways that integrate supportive oncology to optimise quality of life (QoL), functional independence, and patient-centred outcomes. Finally, this review highlights current evidence gaps and proposes future research priorities for developing evidence-based survivorship models for this rapidly expanding patient population. Full article

Immune checkpoint inhibitors targeting the PD-1 pathway have improved outcomes in advanced gastric cancer; however, substantial heterogeneity in treatment response remains. Current prediction strategies mainly rely on pretreatment biomarkers, which provide static assessments and may not capture the evolving interactions between tumor progression and host immunity. This study aimed to develop a dynamic prediction framework integrating longitudinal clinical trajectories and immune remodeling for continuous risk assessment during PD-1 inhibitor therapy. Methods: This retrospective study included 171 patients with gastric cancer receiving PD-1 inhibitor-based treatment. A landmark analysis framework was established using sequential 28-day follow-up windows to predict subsequent progressive disease (PD) or recurrence based on available clinical and immune information. Three nested models were developed: a baseline model (M0), a dynamic clinical model (M1), and an immune-integrated model (M2) incorporating longitudinal lymphocyte subset features. Model performance was evaluated using discrimination, calibration, and internal validation with patient-level resampling strategies. Results: Predictive performance improved progressively with incorporation of longitudinal information. The ROC AUC increased from 0.559 (95% CI, 0.429–0.690) in M0 to 0.737 (95% CI, 0.613–0.852) in M1 and 0.786 (95% CI, 0.681–0.883) in M2. Dynamic clinical information significantly improved discrimination compared with baseline prediction (ΔAUC = 0.178, p = 0.025), while additional immune features further enhanced risk stratification (ΔAUC = 0.049, p = 0.040). Interpretation analysis identified tumor burden evolution, neutrophil-to-lymphocyte ratio trajectories, and immune functional axes involving T-cell, innate cytotoxicity, and humoral immunity as major contributors to risk estimation. Landmark analyses demonstrated the feasibility of continuously updating PD/recurrence risk during treatment. Conclusions: This study establishes a dynamic landmark prediction framework integrating longitudinal clinical trajectories and immune remodeling for continuous risk assessment during PD-1 inhibitor therapy. Dynamic clinical and immune features provided complementary predictive information beyond baseline characteristics, supporting an adaptive approach for precision immunotherapy monitoring in gastric cancer. Full article

Growth factors are molecules that interact with specific membrane receptors and induce cellular proliferation. In malignancy, this growth factor–receptor interaction constitutes one of the “hallmarks of cancer” and may result in uncontrolled cell growth. Proadrenomedullin N-terminal 20 peptide (PAMP) derives from proadrenomedullin and acts as an angiogenic peptide, and recent studies suggest it may be a tumor growth factor. In addition, it has been suggested that CXCR7 may be PAMP’s membrane receptor in particular cell types. Here, we combined advanced docking and molecular dynamic simulation studies to evaluate PAMP’s binding to CXCR7. Then, we used two melanoma cell lines and checked whether PAMP influences their shape, proliferation, migration, and invasion capacities. The signal transduction activated by PAMP was tested by Western blotting, and receptor involvement was investigated with specific inhibitors. This study shows that PAMP binds to active site 1 of CXCR7. It also increases melanoma cell proliferation through an autocrine growth loop. In contrast, PAMP reduced migration and invasion of these cells in a dose-dependent manner. PAMP was also responsible for modifying the actin cytoskeleton of both cell lines, producing a more elongated morphology. In addition, the presence of PAMP elevated ERK and AKT phosphorylation and increased CXCR7 and β-arrestin expression. Furthermore, specific inhibitors confirmed that these effects are mediated by the CXCR7/CXCR4/β-arrestin axis. In summary, we have shown that PAMP acts as a growth factor for melanoma cells while reducing their migration and invasion potential. These effects seem to be mediated by the CXCR7/CXCR4/β-arrestin axis. Altogether, these results suggest that PAMP inhibitors may be used as antitumor agents in melanoma. Full article

Background/Objectives: Breast cancer mortality remains disproportionately high in Eastern Europe, partly due to delayed diagnosis and limited access to organized screening programs. Socioeconomic deprivation and rural residence may contribute to inequalities in breast cancer detection and disease burden at presentation. This study aimed to evaluate the association between sociodemographic disparities and mammographic tumor burden at breast cancer diagnosis within a large regional screening cohort from Eastern Romania. Methods: This retrospective study was conducted within the ONCOFEM regional breast cancer screening initiative between August 2020 and December 2023. A total of 23,886 asymptomatic women aged 50–69 years underwent screening mammography using fixed and mobile digital mammography units. Sociodemographic variables included residential environment (urban/rural) and vulnerability status. Histopathologically confirmed malignant lesions were analyzed regarding maximum mammographic tumor dimension and focality status (unifocal, multifocal, multicentric). Statistical analysis included Mann–Whitney U tests and Chi-square/Fisher exact tests, with p < 0.05 considered statistically significant. Results: The screened population included 12,652 rural women (53.0%) and 11,234 urban women (47.0%). Urban participants demonstrated significantly higher recall rates compared with rural women (7.75% vs. 4.85%, respectively; p < 0.001). Similarly, the Cancer Detection Rate (CDR) was significantly higher in the urban subgroup, reaching 7.21 cancers per 1000 screened women, compared with 4.19 cancers per 1000 screened women in the rural population (p = 0.002). The final analytic cohort included 134 patients with histopathologically confirmed breast cancer, corresponding to 138 malignant lesions. Median tumor size was 25 mm overall. Rural and vulnerable women demonstrated numerically higher proportions of tumors exceeding 20 mm; however, no statistically significant differences were observed regarding maximum tumor dimensions according to residential environment (p = 0.799) or vulnerability (p = 0.934). Multifocal and multicentric disease represented a minority of cases, without significant associations with the sociodemographic subgroup. Conclusions: Although significant urban–rural differences were identified in screening performance metrics, mammographic indicators of tumor burden demonstrated relatively similar distributions across sociodemographic subgroups. The persistently high proportion of tumors exceeding 20 mm across all groups suggests a substantial burden of relatively advanced disease at diagnosis within the Romanian population. No statistically significant disparities in mammographic tumor burden were identified across the analyzed sociodemographic subgroups; however, the present study cannot determine whether the use of mobile mammography units contributed to this observation. Full article

Background/Objectives: Colorectal carcinoma (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with increasing incidence in younger populations. Despite advances in imaging, conventional approaches remain limited by subjective interpretation and insufficient characterization of tumor heterogeneity. Radiomics, particularly in a multiparametric framework integrating computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), has emerged as a promising tool to enhance diagnostic and prognostic performance. This review aims to critically evaluate methodological strategies for optimizing multiparametric radiomics in CRC. Methods: A narrative review was conducted based on a literature search of PubMed/MEDLINE, Scopus, and Web of Science up to March 2026. Studies focusing on CT-, MRI-, and PET-based radiomics in CRC were included. Key methodological aspects analyzed included imaging acquisition and standardization, tumor segmentation techniques, radiomic feature extraction, feature selection methods (e.g., LASSO and PCA), and model validation approaches. Results: Multiparametric radiomics models integrating CT, MRI, and PET consistently demonstrated superior diagnostic accuracy compared to single-modality approaches, particularly in T-staging and lymph node involvement prediction. PET-derived metabolic features further enhanced characterization of tumor biology and improved prognostic stratification, including prediction of progression-free survival (PFS) and overall survival (OS). However, methodological heterogeneity, small sample sizes, and variability in imaging protocols and segmentation practices remain significant limitations affecting reproducibility and generalizability. Conclusions: Multiparametric radiomics represents a powerful advancement in precision oncology for CRC, enabling improved tumor characterization, risk stratification, and personalized treatment planning. Standardization, multicentric validation, and integration with artificial intelligence are essential for successful clinical translation. Full article

Background: Esophagogastric cancer (EGC), encompassing oesophageal, gastroesophageal junction (GEJ), and proximal gastric malignancies, remains a major contributor to global cancer mortality. Neoadjuvant therapy, chemotherapy (CT) or chemoradiotherapy (CRT) is now standard for locally advanced, resectable disease. However, variability in treatment response and survival outcomes continues to challenge therapeutic optimisation. Methods: This systematic review followed the PRISMA 2020 guidelines and included studies published between January 2020 and September 2025. Eligible studies enrolled adult patients with resectable EGC treated with neoadjuvant CT or CRT, reporting data on pathological response (pathological complete response (pCR) or tumour regression grade (TRG)) and survival outcomes [overall survival (OS), disease-free survival (DFS)]. Sixty studies (18 randomised controlled trials and 42 cohort analyses) were included for qualitative synthesis. Results: Across all regimens, pCR rates ranged from 8% to 49%, with CRT achieving higher pCR (mean 33%) and major TRG response (63%) compared to CT alone (pCR 22%, TRG 48%). Immunotherapy-enhanced protocols (IO-CRT and IO-CT) demonstrated the most promising outcomes, reaching mean pCR rates up to 48–50%. Patients with complete or major regression consistently achieved superior OS and DFS, confirming pathological response as a consistent prognostic marker for long-term survival. Significant clinical heterogeneity was observed across histological subtypes (SCC vs. AC), treatment intensity, and surgical timing, while methodological heterogeneity stemmed from variations in TRG systems, follow-up duration, and reporting standards. Conclusions: Pathological response is consistently associated with survival following neoadjuvant therapy in EGC, yet its predictive power is modulated by tumour histology and treatment modality. Standardisation of TRG assessment, integration of molecular biomarkers, and harmonisation of study design are essential for improving comparability and advancing personalised, multimodal strategies in oesophagogastric oncology. Full article

Thanks to the rapid development of advanced analytical methods, researchers can now identify new, so far unknown applications for existing drugs. This expanding knowledge about the mechanisms of drug action, including interactions with various molecules and molecular pathways, not only enables more effective use of available therapies but also reduces both the time and cost of developing new therapeutic options. One of the proteins reported to interact with numerous drugs and chemicals is Translationally Controlled Tumor Protein (TCTP). Numerous studies have demonstrated that TCTP plays a crucial role in diverse biological processes, including cell growth, cell cycle regulation, cellular proliferation, allergic reactions, stress response, inhibition of apoptosis, calcium ion binding, interacting with microtubules and actin microfilaments, the progression of various cancers, and tumor reversion. Therefore, this review article aims to compile a list of drugs and substances shown to interact with TCTP and that, given TCTP’s numerous cellular functions, could be repurposed for other therapies. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide despite advances in screening, surgical techniques, and systemic therapies. In recent years, exosomes—nanoscale extracellular vesicles involved in intercellular communication—have emerged as critical regulators of CRC biology. Exosomes mediate tumor progression, metastatic dissemination, immune evasion, and therapeutic resistance through the transfer of bioactive molecules including proteins, lipids, and non-coding RNAs. Moreover, exosomes have gained increasing attention as promising liquid biopsy tools and therapeutic platforms due to their stability, biocompatibility, and ability to reflect tumor molecular dynamics. This review provides a comprehensive overview of exosome biogenesis, molecular composition, and their functional roles in CRC pathogenesis. We further discuss their diagnostic and prognostic value, involvement in therapeutic resistance, and emerging therapeutic applications, with particular emphasis on translational and surgical oncology implications. Finally, we highlight current limitations and future perspectives for clinical integration of exosome-based strategies in CRC management. Full article

Endometrial and cervical cancers can recur from subclinical disease not evident on routine surveillance. This narrative review critically evaluates liquid biopsy for minimal residual disease (MRD) assessment and recurrence monitoring. Post-treatment human papillomavirus (HPV) circulating tumor DNA (ctDNA) in cervical cancer has the strongest disease-specific prospective evidence of clinical validity; persistent detection is strongly associated with recurrence, but moderate sensitivity and false-negative results do not support treatment de-escalation on negativity alone. With regard to endometrial cancer, perioperative ctDNA has prognostic support from an 11-study, 1298-patient meta-analysis and additional cohorts, although assay heterogeneity and limited independent replication constrain clinical readiness. Postoperative positivity generally shows stronger associations than preoperative detection. Cervicovaginal and urine DNA-methylation studies provide preliminary evidence for detecting established recurrence, especially local recurrence, but not prospective molecular lead time or clinical utility. Digital PCR, disease-specific fixed panels, tumor-informed assays, and error-corrected sequencing serve distinct settings; broad pan-cancer plasma profiling remains mainly an advanced-disease tool. Circulating tumor cells, extracellular vesicles, microRNAs, tumor-educated platelets, and fragmentomics remain exploratory. Liquid biopsy should remain an investigational adjunct until prospective trials show that acting on molecular findings improves outcomes. Full article

Background/Objectives: End-of-life (EOL) preparedness remains critically understudied among Hispanic patients with advanced breast cancer and their patient–caregiver dyads, despite evidence that preparedness significantly influences quality of life, care decisions, and caregiver well-being. This study aimed to explore how Hispanic patient–caregiver dyads conceptualize and experience EOL preparedness. Methods: A qualitative descriptive design was employed, guided by the Dyadic Cancer Outcomes Framework, which highlights patient and caregiver characteristics, relationship processes, individual and relational outcomes, the cancer care trajectory, and the broader social context as interrelated influences on dyadic experience. Semi-structured individual interviews were conducted in Spanish with 11 metastatic patient–caregiver dyads (n = 22 participants) recruited through Ponce Health Sciences University and the Ponce Research Institute in Puerto Rico. Data were analyzed using codebook thematic analysis in NVivo 15, with themes interpreted through the framework’s components. Results: Six interdependent themes of EOL preparedness were identified: psychological and emotional, spiritual, informational, practical, physical, and caregiver role preparedness. Spiritual preparedness, grounded in faith, prayer, and surrender to divine will, functioned as the foundational axis organizing all other themes. Preparedness was dynamic and turning-point-driven, challenged anew at each stage of disease progression. Financial vulnerability, caregiver invisibility within formal care systems, and insufficient anticipatory information were identified as primary barriers. Family support and faith communities were the most consistently cited facilitators. Conclusions: The findings yield the first grounded, dyadic conceptualization of EOL preparedness with Hispanic advanced breast cancer patient–caregiver dyads. We propose a formal definition positioning preparedness as a dynamic, multidimensional, relationally embedded, and spiritually anchored process that is fundamentally interdependent between patient and caregiver. These results directly inform the development of a culturally tailored, dyadic EOL preparedness intervention for this underserved population. Full article

Objectives: We evaluated the performance of mammography-based radiomics in prediction of clinical nodal status, clinical tumor stage, clinical disease stage, status of the PIK3CA mutation and concordance with the radiologist-assessed BI-RADS category. Mammography is often the first imaging modality performed in the screening or diagnostic workup of breast cancer. Materials and Methods: In this single-center retrospective study, we included 102 histopathologically confirmed cases of breast cancer from 100 patients. The tumor region and whole-breast parenchyma were contoured on 368 craniocaudal and mediolateral-oblique mammograms. Cases were temporally split into training and test sets by histopathological diagnosis date (training: 70%, held-out test: 30%). Six linear models were tuned by 5-fold x 3-repeat stratified cross-validation. The winning model per endpoint was applied once to the test set. We report AUCs with 95% confidence intervals, permutation p-values and Benjamini–Hochberg false discovery rate (BH-FDR) correction across five endpoints. Results: Three of the studied endpoints reached significance after BH-FDR correction: clinical nodal status (cN0 vs. cN-positive; AUC: 0.726 (95% CI: 0.501–0.886)), clinical tumor stage (cT1-2 vs. cT3-4; AUC: 0.792 (95% CI: 0.575–0.929)) and overall disease stage (I–II vs. III–IV; AUC: 0.778 (95% CI: 0.572–0.917)). Mammography-based radiomics failed to predict the presence of PIK3CA mutation and concordance with radiologist-assessed BI-RADS category. Conclusions: Mammography-based radiomics has shown a hypothesis-generating discriminative value for differentiation between cN-negative and cN-positive disease, early from advanced clinical tumor stage, and early from advanced overall disease stage in breast cancer. Mammography-based radiomics did not predict PIK3CA status and did not discriminate between radiologist-assessed BI-RADS 4 and 5 groups. Full article

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide, largely because it is diagnosed late. Diagnosis typically relies on imaging and biopsy, but only after tumors have advanced, which reduces treatment effectiveness. Current biochemical biomarkers are limited to CA19-9, which is more useful for prognosis and monitoring than for diagnosis. Circulating miRNAs may offer minimally invasive complementary biomarkers for PDAC diagnosis, potentially accounting for ethnic and treatment-related variables. We performed small RNA sequencing on plasma from five non-metastatic-stage and five metastatic-stage PDAC patients and 10 healthy controls to generate an exploratory miRNA profile. Candidate miRNAs were then validated by RT-qPCR in an independent cohort of 70 PDAC patients and 106 healthy controls, and nine miRNAs showed promising differential plasma expression. Notably, miRNA484 and miRNA335-5p were associated with PDAC in CA19-9-negative patients, with ROC AUCs of 0.984 and 0.88, respectively. Overall, these results indicate that miRNA484 and miRNA335-5p may have clinical value as complementary biomarkers for PDAC patients who are CA19-9-negative. Full article

Background: Autophagy is a process that diversely impacts the stages of both tumor initiation and progression. Elucidating the molecular mechanisms underlying autophagy and its role in tumorigenesis is a key component of anticancer strategies in both prostate cancer and other malignancies. Because advanced prostate cancer frequently exploits enhanced autophagy as a defense mechanism against therapy-induced stress (e.g., from abiraterone), the pharmacological modulation of miRNA levels presents a tremendous opportunity to block the tumor’s escape route and overcome drug resistance. Methods: A comprehensive literature review was conducted to evaluate the molecular pathways determining cancer cell survival and death. The analysis focused on the dual nature of autophagy (functioning as a ‘double-edged sword’) within the tumor microenvironment, microRNA (miRNA) regulatory networks, and the efficacy of synergistic therapeutic strategies in overcoming treatment resistance. Results: The primary focus of this paper is the dual and complex role of autophagy, which serves, on the one hand, as a cellular protective shield against metabolic stress—thereby facilitating metastasis—and, on the other hand, as a potential pathway leading to autophagic cell death. The progression of this crucial process is regulated by intricate interactions (crosstalk) with apoptotic pathways, mediated by Bcl-2 family proteins, key kinases (such as mTOR, JNK, and DAPK), and transcription factors, such as p53. Furthermore, the autophagic machinery is precisely regulated by specific miRNA molecules (e.g., miR-21, miR-141, and miR-375). These not only act as crucial intracellular modulators of autophagy but also serve as promising circulating biomarkers, enabling the monitoring of this process’s activity throughout disease progression. Conclusions: Autophagy, and in particular its modulation via miRNA signaling networks, represents a major and highly promising translational target. By directly impairing this autophagic survival mechanism, ‘double-hit’ combination therapies—integrating autophagy inhibitors (such as hydroxychloroquine or VPS34 inhibitors) with standard antiandrogen or cytotoxic agents—demonstrate promising preclinical potential in overcoming treatment resistance and favorably modulating the immune microenvironment in advanced prostate cancer. Full article

Background: Colorectal neoplasia in adults younger than 50 years has attracted increasing clinical attention because of the rising incidence of early-onset colorectal cancer. However, the clinicopathological characteristics of colorectal lesions detected in younger adults remain incompletely described. This study aimed to characterize the clinical, anatomical, and histopathological features of colorectal neoplasia in adults younger than 50 years undergoing colonoscopy. Methods: This retrospective single-center study included adults aged 18–49 years who underwent complete colonoscopy between January 2018 and December 2023. After exclusion of individuals with normal colonoscopy findings, 152 patients with at least one colorectal lesion were included. Lesions were classified as benign, advanced, or malignant according to established histopathological criteria. Demographic, endoscopic, and pathological characteristics were analyzed and compared across lesion categories. Results: Among 152 patients, 83 (54.6%) had benign lesions, 64 (42.1%) had advanced neoplasia, and 5 (3.3%) had malignant lesions. Advanced lesions were observed predominantly in individuals aged 40–49 years. Most lesions were detected in symptomatic patients undergoing clinically indicated colonoscopy. Histopathological evaluation demonstrated a higher frequency of villous/tubulovillous adenomas, sessile serrated lesions, and high-grade dysplasia among advanced lesions. Larger lesion size was strongly associated with advanced pathological features (p < 0.001). In multivariable analysis, patients aged 30–39 years had significantly lower odds of advanced or malignant neoplasia than those aged 40–49 years, whereas no independent associations were observed for sex, smoking status, alcohol use, family history of colorectal cancer, or lesion location. Conclusions: In this selected cohort of adults younger than 50 years with detected colorectal lesions undergoing clinically indicated colonoscopy, advanced neoplasia represented a substantial proportion of cases. These findings should not be extrapolated to the general population of adults younger than 50 years or to screening cohorts. Full article