Search Results (168)

Prostate cancer accounts for approximately 1.5 million new diagnoses and 400,000 deaths every year worldwide, and demographic projections indicate a near-doubling of both figures by 2040. Despite existing treatments, 10–20% of patients eventually progress to metastatic castration-resistant disease (mCRPC). The median overall survival (OS) after progression to mCPRC drops to 24 months, and efficacy drops severely after each additional line of treatment. Omics platforms have reached advanced levels and enable the acquisition of high-resolution large datasets that can provide insights into the molecular mechanisms underlying PCa pathology. Genomics, especially DDR (DNA damage response) gene alterations, detected via tissue and/or circulating tumor DNA, efficiently guides therapy in advanced prostate cancer. Given recent developments, we have performed a comprehensive literature search to cover recent research and clinical trial reports (over the last five years) that integrate omics along three converging trajectories in therapeutic development: (i) predicting response to approved agents with demonstrated survival benefits, (ii) stratifying patients to receive therapies in clinical trials, (iii) guiding drug development as part of drug repurposing frameworks. Collectively, this review is intended to serve as a comprehensive resource of recent advancements in omics-guided therapies for advanced prostate cancer, a clinical setting with existing clinical needs and poor outcomes. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal malignancies, with a five-year survival rate below 12%, largely attributable to its asymptomatic onset, late-stage diagnosis, and limited curative treatment options. Although PDAC accounts for approximately 3% of all cancers, it is projected to become the second leading cause of cancer-related mortality in the United States by 2030. A major contributor to its dismal prognosis is the lack of validated early detection strategies for asymptomatic individuals. In this review, we present a comprehensive synthesis of current advances in the early detection of PDAC, with a focus on the identification of high-risk populations, novel biomarker platforms, advanced imaging modalities, and artificial intelligence (AI)-driven tools. We highlight high-risk groups—such as those with new-onset diabetes after age 50, pancreatic steatosis, chronic pancreatitis, cystic precursor lesions, and hereditary cancer syndromes—as priority populations for targeted surveillance. Novel biomarker panels, including circulating tumor DNA (ctDNA), miRNAs, and exosomes, have demonstrated improved diagnostic accuracy in early-stage disease. Recent developments in imaging, such as multiparametric MRI, contrast-enhanced endoscopic ultrasound, and molecular imaging, offer improved sensitivity in detecting small or precursor lesions. AI-enhanced radiomics and machine learning models applied to prediagnostic CT scans and electronic health records are emerging as valuable tools for risk prediction prior to clinical presentation. We further refine the Define–Enrich–Find (DEF) framework to propose a clinically actionable strategy that integrates these innovations. Collectively, these advances pave the way for personalized, multimodal surveillance strategies with the potential to improve outcomes in this historically challenging malignancy. Full article

Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article

Neglecting preventive healthcare policies has contributed to the global surge in chronic diseases, increased hospitalizations, declining quality of care, and escalating costs. Non-communicable diseases (NCDs)—notably cardiovascular conditions, diabetes, and cancer—consume over 80% of healthcare expenditure and account for more than 60% of global deaths, which are projected to exceed 75% by 2030. Poor diets, sedentary lifestyles, regulatory loopholes, and underfunded public health initiatives are driving this crisis. Compounding the issue are flawed policies, congressional lobbying, and conflicts of interest that prioritize costly, hospital-based, symptom-driven care over identifying and treating to eliminate root causes and disease prevention. Regulatory agencies are failing to deliver their intended functions. For instance, the U.S. Food and Drug Administration’s (FDA) broad oversight across drugs, devices, food, and supplements has resulted in inefficiencies, reduced transparency, and public safety risks. This broad mandate has allowed the release of unsafe drugs, food additives, and supplements, contributing to the rising childhood diseases, the burden of chronic illness, and over-medicalization. The author proposes separating oversight responsibilities: transferring authority over food, supplements, and OTC products to a new Food and Nutraceutical Agency (FNA), allowing the FDA to be restructured as the Drug and Device Agency (DDA), to refocus on pharmaceuticals and medical devices. While complete reform requires Congressional action, interim policy shifts are urgently needed to improve public health. Broader structural changes—including overhauling the Affordable Care Act, eliminating waste and fraud, redesigning regulatory and insurance systems, and eliminating intermediaries are essential to reducing costs, improving care, and transforming national and global health outcomes. The information provided herein can serve as a White Paper to help reform health agencies and healthcare systems for greater efficiency and lower costs in the USA and globally. Full article

Age-related macular degeneration (AMD) is a common cause of blindness worldwide, and it is projected to affect several million individuals by 2040. The human retinal pigment epithelium (hRPE) degenerates in dry AMD, prompting the need to develop stem cell therapies to replace the lost tissue by autologous transplantation and restore the visual function. Nevertheless, the molecular factors behind the hRPE cell fate determination have not been elucidated. Here we identify all molecular determinants of the hRPE cell fate identity by comprehensive and unbiased screening of predicted pioneer factors in the human genome: such TFs mediate coordinated transitions in chromatin accessibility and transcriptional outcome along three major stages of the hRPE genesis. Furthermore, we compile a complete census of all transcription factor-specific binding sites by footprinting analysis of the human epigenome along the RPE developmental trajectory. Gene regulatory networks were found to be involved in cellular responses to glucose and hypoxia, RPE nitrosative stress, type II epithelial-to-mesenchymal transition (EMT), and type III tumorigenic EMT, providing routes for therapeutic intervention on pleiotropic targets dysregulated in AMD, diabetic retinopathy, and cancer progression. Genome editing technologies may leverage this repository to devise functional screenings of regulatory elements and pharmacogenomic therapies in complex diseases, paving the way for strategies in precision medicine. Full article

Synchrotron radiation light sources have been successfully utilized in material science, biomedicine, and other fields due to their high intensity, excellent monochromaticity, coherence, and collimation. In recent years, synchrotron radiation has significantly expedited the advancement of medical applications, particularly through innovations in imaging and radiotherapy. For instance, synchrotron X-ray imaging has enabled high-contrast and spatial–temporal resolution images for early-stage diagnosis of breast cancer and cardiovascular diseases, offering superior diagnostic accuracy compared to conventional methods. Additionally, novel synchrotron radiation-based radiotherapy techniques, such as microbeam therapy and stereotactic radiotherapy, have shown great potential for clinical application by enabling precise tumor targeting while minimizing damage to surrounding healthy tissues. These advancements are projected to redefine imaging diagnostics and therapeutic strategies, particularly for resistant cancers, by offering enhanced precision, reduced radiation doses, and improved therapeutic outcomes. This review provides an overview of synchrotron radiation beamline characteristics, recent breakthroughs in imaging and radiotherapy, and their emerging applications in treating heart, breast, lung, bone, and brain conditions. Full article

Aging is the primary risk factor for chronic diseases such as cardiovascular disease, cancer, and dementia. However, chronological age alone fails to capture individual variability in aging trajectories and disease susceptibility. Recent advances in epigenetic clocks—DNA methylation-based models that estimate biological age—have opened new possibilities for personalized and preventive medicine. This review explores the clinical potential of epigenetic clocks and EpiScores, composite biomarkers that predict health risks and physiological status. We present a comparative evaluation of widely used epigenetic clocks, including Horvath, GrimAge, PhenoAge, and DunedinPACE, and summarize their predictive performance for mortality, cognitive decline, and cardiovascular outcomes. EpiScores linked to inflammation, glycemic control, and immunosenescence are highlighted as tools for stratified risk assessment. When integrated with multi-omics data and electronic health records, these measures enhance the precision of population health management. Special emphasis is placed on applications in longevity clinics and anti-aging clinics, community-based care, and national health checkup systems. We also explore global standardization efforts and ethical considerations, as well as Japan’s unique initiatives—including the “Aging Measurement” project at the Osaka-Kansai Expo 2025. Furthermore, we propose the development of a Global Health and Aging Index that integrates the biological, functional, and subjective dimensions of aging, aligned with the WHO concept of Intrinsic Capacity. In conclusion, epigenetic clocks and EpiScores represent transformative tools for shifting from reactive treatment to proactive health optimization, and from chronological to biological metrics in aging science and public health policy. Full article

Sexual dysfunction following abdominal or pelvic surgery is a significant concern that impacts the quality of life (QoL) for both men and women. This paper explores the multifaceted challenges and re-educational strategies associated with post-surgical sexual dysfunction. It highlights the physical and psychological repercussions of surgeries such as hysterectomies, pelvic organ prolapse repairs, radical prostatectomies, and rectal cancer resections. These procedures often lead to complications like dyspareunia, erectile dysfunction, and altered body image, necessitating comprehensive re-educational approaches. The review emphasizes the importance of tailored interventions, including pelvic floor muscle training (PFMT), biofeedback, manual therapy, and advanced techniques like botulinum toxin injections and sacral neuromodulation. For men, strategies such as phosphodiesterase type 5 inhibitors (PDE5i), vacuum erection devices (VEDs), intracavernosal injections, and penile prostheses are explored for their efficacy in restoring erectile function. Psychological support, including cognitive–behavioral therapy and couples counseling, is underscored as essential to addressing emotional and relational aspects of recovery. A multidisciplinary approach involving physiatrists, urologists, gynecologists, physiotherapists, psychologists, and sexual health counselors is advocated for to optimize outcomes. Integrating physical therapy modalities, as well as psychological and relational therapies, into individual rehabilitation projects is crucial for improving sexual function and overall QoL post-surgery. Future research should focus on refining these established strategies and investigating the potential of innovative therapeutic modalities. Full article

Cancer has rapidly emerged as a leading global cause of premature mortality, with significant economic implications projected to reach USD 25.2 trillion from 2020 to 2050. Among the various types of cancer, primary bone cancers, though uncommon, are projected to see nearly 4000 new cases diagnosed in the United States in 2024. The complexity of treating bone cancer arises from its rarity, diversity, and the challenges associated with surgical interventions, metastatic spread, and post-operative complications. Advancements in bone tissue engineering (BTE) have introduced innovative therapeutic approaches to promote bone regeneration and address tumor recurrence. This interdisciplinary field integrates biomaterials, scaffolds, and gene therapy, utilizing technologies such as 3D bioprinting to create custom scaffolds that facilitate cellular activities essential for tissue regeneration. Recent developments in biodegradable, bioactive materials aim to enhance the biocompatibility and effectiveness of scaffolds, while nanotechnology presents promising avenues for targeted drug delivery and improved therapeutic outcomes. This review outlines the current landscape of BTE, highlighting scaffold fabrication techniques, the advantages of incorporating stem cell and gene therapies, and future directions, including the integration of artificial intelligence in scaffold design for personalized medicine in orthopedic oncology. This work underscores the necessity for ongoing research and innovation, aiming to improve therapeutic strategies specifically designed to address the unique challenges posed by bone sarcomas and metastatic cancers. Full article

Background/Objectives: Cancer and related treatments can impair body composition (BC), increasing the risk of malnutrition and sarcopenia, poor prognosis, and Health-Related Quality of Life (HRQoL). To enhance BC parameter interpretation through Bioelectrical Impedance Analysis (BIA), we developed a predictive model based on unsupervised approaches including Principal Component Analysis (PCA) and k-means clustering for sarcopenia risk in cancer patients at the Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale” (Naples). Methods: Sarcopenia and malnutrition risks were assessed using the NRS-2002 and SARC-F questionnaires, anthropometric measurements, and BIA. HRQoL was evaluated with the EORTC QLQ-C30 questionnaire. PCA and clustering analysis were performed to identify different BC profiles. Results: Data from 879 cancer patients (mean age: 63 ± 12.5 years) were collected: 117 patients (13%) and 128 (15%) were at risk of malnutrition and sarcopenia, respectively. PCA analysis identified three main components, and k-means determined three clusters, namely HMP (High Muscle Profile), MMP (Moderate Muscle Profile), and LMP (Low Muscle Profile). Patients in LMP were older, with a higher prevalence of comorbidities, malnutrition, and sarcopenia. In the multivariable analysis, age, lung cancer site, diabetes, and malnutrition risk were significantly associated with an increased risk of sarcopenia; among the clusters, patients in LMP had an increased risk of sarcopenia (+62%, p = 0.006). Conclusions: The NUTRISCREEN project, part of the ONCOCAMP study (ClinicalTrials.gov ID: NCT06270602), provides a personalized nutritional pathway for early screening of malnutrition and sarcopenia. Using an unsupervised approach, we provide distinct BC profiles and valuable insights into the factors associated with sarcopenia risk. This approach in clinical practice could help define risk categories, ensure the most appropriate nutritional strategies, and improve patient outcomes by providing data-driven care. Full article

Background: Disulfide-dependent cell death, known as disulfide death, plays a pivotal regulatory role in the onset and progression of various cancers including pancreatic cancer. Despite its significance, little attention has been given to the study of disulfide death-related long non-coding RNAs (lncRNAs) in pancreatic cancer development and progression. Methods: This study utilized data from the Cancer Genome Atlas Project (TCGA) to analyze the transcriptome of pancreatic cancer. Co-expression analysis of genes associated with disulfide death was performed and six lncRNAs closely linked to disulfide death were identified through univariate and multivariate analysis. These lncRNAs were used to develop clinical prognostic models. The prognostic value of this model was then analyzed and further investigations included pathway enrichment analysis, tumor mutation load analysis, immune cell infiltration analysis, analysis of the tumor microenvironment (TME), and drug sensitivity analysis. Results: The developed prognostic model based on disulfide-associated lncRNAs exhibited significant prognostic value, allowing for reliable predictions of patient outcomes in pancreatic adenocarcinoma (PAAD). The analysis revealed that the six identified lncRNAs serve as independent prognostic factors, significantly correlating with patient survival and recurrence rates. Additionally, findings indicated notable differences in immune cell infiltration and drug sensitivity between high-risk and low-risk patient groups, suggesting potential therapeutic targets for enhancing treatment efficacy. Conclusions: Our findings revealed six disulfide death-associated lncRNAs with independent prognostic value, offering a crucial indicator for predicting the prognosis of pancreatic adenocarcinoma (PAAD) patients. Additionally, the analysis of tumor immune invasion and drug sensitivity provides a novel avenue for controlling tumor invasion and metastasis as well as reducing drug tolerance. Full article

Huntingtin-interacting protein 1-related (HIP1R) shares some function similarities with HIP1, and HIP1 regulates arthritis and RA fibroblast-like synoviocytes (FLS) invasiveness. Therefore, we hypothesized that HIP1R might be involved in the regulation of FLS phenotypes and molecular processes relevant to RA. siRNA was used to knockdown HIP1R, HIP1 or control in RA FLS, followed by cell studies for invasion in Matrigel, migration, proliferation, and adhesion. RNA was sequenced and analyzed. HIP1R knockdown significantly reduced RA FLS invasiveness and migration (p < 0.05). The DEGs in siRNA HIP1R had an enrichment for GO processes “astrocyte and glial cell projection”, “small GTPase signaling”, and “PDGFR signaling”. The most significantly DEGs had decreased expression in siRNA HIP1R and included AKT1S1, GABBR2, GPR56, and TXNDC12. siRNA HIP1 RA FLS had an enrichment for the “Rap1 signaling pathway” and “Growth factor receptor binding”. The most significantly DEGs in HIP1 siRNA included FGF2, PGF, and SLC39A8. HIP1R and HIP1 DEG lists had a greater than expected number of similar genes (p = 0.0015), suggesting that, despite the major differences detected, both have partially overlapping functions in RA FLS. The most significantly DEGs in both HIP1R and HIP1 analyses are involved in cancer cell behaviors and outcomes. HIP1R is a new gene implicated in RA FLS invasiveness and migration, and regulates unique pathways and cell processes relevant to both RA as well as cancer biology. Our study provides new insight into processes implicated in FLS invasiveness, which is relevant for joint damage in RA, and identify new potential gene targets for FLS-specific treatments. Full article

Background/Objectives: Gastric cancer remains a leading cause of cancer-related deaths worldwide and surgical resection represents the mainstay of treatment procedures. However, despite the advancements noted in the field of surgical oncology, perioperative complications and variability in the perioperative care provided persist. To address the challenges caused by non-standardized perioperative care for gastric surgery across European healthcare systems, the EUropean PErioperative MEdical Networking (EUPEMEN) protocol has been developed. The present study concisely provides the EUPEMEN protocol’s development, implementation, and impact on perioperative management in gastric resections. Methods: The EUPEMEN protocol was developed through a multidisciplinary collaboration involving five academic healthcare professionals from four European countries. The main activities of the collaborative group included a literature review, consensus development, the creation of multimodal rehabilitation manuals, and the development of an online learning platform. The EUPEMEN project aims for the uniform adoption of evidence-based practices across preoperative, intraoperative, and postoperative phases, leading in nutritional, psychological, and physiological optimization. Results: The implementation of the EUPEMEN protocol aims to optimize perioperative outcomes, including reduced postoperative complications, a shorter length of hospitalization, and improved recovery trajectories. The above have been achieved through structured guidelines that ensure consistent care delivery across diverse healthcare settings and tools such as rehabilitation manuals and a free-access online educational platform. Conclusions: The EUPEMEN protocol represents a new standard for perioperative care in the field of gastric surgery that is based on multidisciplinary collaboration and evidence-based practices. While challenges such as resource constraints and variability in adherence remain, the protocol demonstrates significant potential to improve patient outcomes and streamline perioperative management. Future research should focus on long-term effects and adaptation challenges in the setting of non-European healthcare systems. Full article

Objective: The aim of the NALOPOOL project was to assess the efficacy and safety of naloxegol in patients with cancer pain who exhibited opioid-induced constipation (OIC) and were treated under real-world conditions. Methods: We pooled individual patient data from three multicenter observational studies conducted with naloxegol in patients with cancer who exhibited OIC and were prescribed naloxegol under real-world conditions. Efficacy outcomes were evaluated after 4 weeks of treatment. All analyses were performed via a visit-wise approach. Heterogeneity was assessed via Cochran’s Q-test or Levene’s test. Results: Spontaneous bowel movements (SBM) response (≥3 SBM per week and an increase of ≥1 from baseline; three studies) was reported in 223 of 314 evaluable patients (71%, 95% CI 66–76); clinically relevant improvement in the Patient Assessment of Constipation Quality-of-Life Questionnaire (>0.5 points; three studies) occurred in 179 of 299 evaluable patients (60%, 95% CI 56–74) and in the Patient Assessment of Constipation Symptoms (>0.5 points; two studies) was reported in 131 of 190 evaluable patients (69%, 95% CI 62–76); and clinically relevant improvement in the Bowel Function Index (score ≥ 12 points at the endpoint; two studies;) was reported in 133 of 195 evaluable patients (68%, 95% CI 62–75). No significant heterogeneity was found for any efficacy outcome. The pooled proportion of patients who discontinued the drug owing to adverse reactions was 6.1% (95% CI 3.8% to 8.4%). Conclusions: Our results support the use of naloxegol for the management of OIC in patients with cancer pain who do not respond to laxative treatment. Full article

Women diagnosed with early-stage breast cancer can develop metastatic disease following successful initial treatment, with bone being the most common site of metastases. The Breast to Bone (B2B) cohort study of early-stage breast cancer patients was established as a research platform to study the basic biology of breast cancer to bone metastasis and to identify the factors that could improve prevention, early detection and treatment for this debilitating and incurable disease. The B2B cohort includes 478 women diagnosed with incident primary breast cancer (stages I to III) who were recruited from Calgary, Alberta and surrounding areas between February 2010 and July 2015. Four projects have been conducted to date, utilizing data and samples from this cohort. These studies have found the following: (a) women with insufficient or deficient levels of vitamin D (25[OH]D) concentrations in pretreatment serum samples had larger tumors and higher breast cancer grades, (b) several metabolomic biomarkers and cytokines were associated with tumor characteristics and time to recurrence, (c) additional biomarkers were found to be predictive for the high risk of bone metastasis and (d) circulating progastrin (hPG80) was associated with multiple survival outcomes. These research studies and future ones will provide new evidence on bone metastasis etiology in women diagnosed with early-stage breast cancer, improve identification of those at high risk and contribute to personalized treatment and prevention options. Full article