Search Results (8,677)

Targeted synergistic therapies represent a rapidly developing branch of oncology. The emergence of novel targeting agents allows for modulation of an ever-larger set of cellular pathways. The Unfolded Protein Response (UPR) is a key element of cellular proteostasis that is significantly hyperactivated in a wide range of cancer cell types, especially those with high secretory activity. As cancer cells are especially vulnerable to endoplasmic reticulum stress (ER Stress), they become heavily dependent on UPR function to maintain homeostasis. A wide number of pharmacologic agents can stimulate the UPR and shift it from its initial pro-survival phase to the terminal pro-apoptotic phase. Key strategies include the use of UPR feedback inhibitors (e.g., GRP78 antagonists), direct pathway inhibitors targeting the PERK or IRE1α branches, and signal pathway modulators (e.g., TKIs and BTK inhibitors) that indirectly exacerbate proteotoxic stress. In this study we provide a mechanistic framework where we classify synergistic therapies based on their mechanism of action and explore how they influence ER Stress and UPR activation. Evidence synthesized from these studies suggests that synergistic combinations can overcome therapeutic resistance and selectively induce apoptosis in cancer cells characterized by high proteotoxic stress. Full article

Hashimoto thyroiditis (HT) coexists with differentiated thyroid carcinoma (DTC), particularly papillary thyroid carcinoma, in approximately 25% of cases. However, the impact of this association on DTC outcomes remains controversial. The aim of this study was to analyze the influence of Hashimoto thyroiditis on disease-specific survival (DSS) and recurrence-free survival (RFS) in DTC patients. Methods: A retrospective study conducted at our institution between 2007 and 2020 analyzed 707 DTC patients treated with surgery and/or I-131 therapy. Cox proportional hazards regression was used to identify independent predictors, including sex, age, tumor histology, HT status, and initial TNM stage. Results: Among 707 DTC patients, 628 (88.8%) had papillary cancer, 582 (82.3%) were female, 395 (55.9%) were <55 years old; HT coexisted in 137 (19.4%) patients. During follow-up, 23 (3.25%) developed recurrent disease; at last follow-up, 638 (90.2%) were alive. Initial distant metastases (p < 0.001) and higher T stage (p = 0.002) independently predicted worse DSS. For RFS, male sex (p = 0.015), higher T stage (p = 0.018), and lymph node involvement (p = 0.023) independently predicted an increased risk of recurrence. HT was not an independent predictor of DSS (HR 0.97, 95% CI 0.21–4.52; p = 0.964) or recurrence (HR 0.36, 95% CI 0.05–2.73; p = 0.322). Conclusions: Although Hashimoto thyroiditis was associated with favorable clinicopathological features, it was not independently associated with disease-specific or recurrence-free survival. Conventional staging parameters, particularly tumor stage, remain the principal determinants of prognosis in differentiated thyroid cancer. Full article

Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice. Full article

Breast cancer remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide. The growing interest in natural bioactive compounds has highlighted plant-derived phytochemicals as promising agents for cancer prevention and adjunctive therapy due to their pleiotropic biological activities and relatively low toxicity. In parallel, increasing attention has been directed toward agro-industrial by-products generated during food processing, which represent abundant and sustainable sources of valuable phytochemicals. This review provides a comprehensive overview of recent advances in the identification, extraction, and biological evaluation of phytochemicals derived from plants and agro-industrial residues, using pomegranate (Punica granatum) peels, onion (Allium cepa) skins, and citrus by-products as representative examples of phytochemical-rich agro-industrial residues. These by-products are rich in polyphenols, flavonoids, and other secondary metabolites—including punicalagins, ellagic acid, quercetin, hesperidin, and naringin—that have demonstrated significant antioxidant, anti-inflammatory, and anticancer properties. Recent in vitro and in vivo studies indicate that these compounds can modulate key molecular pathways involved in breast cancer initiation and progression, such as oxidative stress regulation, apoptosis induction, inhibition of cell proliferation, and suppression of signaling cascades including PI3K/Akt, NF-κB, and MAPK pathways. Furthermore, the valorization of agro-industrial waste offers a sustainable strategy to recover high-value bioactive compounds while reducing environmental impact. Overall, phytochemicals obtained from plant materials and food processing by-products represent promising functional agents for breast cancer prevention and therapy, although further studies are required to improve bioavailability, elucidate mechanisms of action, and validate their clinical potential. Full article

Background/Objectives: There is limited data on treatment outcomes under immune checkpoint inhibitor (ICI) administration in solid organ transplant recipients (sOTRs). This study aims to evaluate cancer outcome and allograft rejection risk in sOTRs receiving ICI. Methods: This is a retrospective multicenter study. The data had been collected within the Swiss Transplant Cohort Study (STCS) database. We searched for matching individuals from May 2008 up to the end of 2024. The primary outcomes were treatment response and survival; the secondary outcome was allograft rejection. Additional analyses included associated factors such as tumor, transplant, and treatment characteristics. Results: We identified ten patients, six of whom received a kidney allograft, while the remaining four received a liver, lung, pancreas, or combined kidney–pancreas transplant. Treatment response was achieved in half of the sOTRs, with a complete response (CR) in three and prolonged stable disease (SD) in two patients. CR was achieved in all three patients after only a few infusions. At the time of data analysis, four out of ten patients were still alive. Graft rejection occurred in six out of ten cases, five of which occurred after the first cycle of ICI administration. Conclusions: Data is limited and definitive conclusions from this study cannot be drawn given the limited sample size. However, ICI displays promising effects on cancer outcomes in sOTRs with advanced malignancies. The study’s findings demonstrate an overall response in half of sOTRs, but with graft rejection occurring in a similar number of patients. We propose initiating immunotherapy as early as possible, given the promising results, particularly in patients with kidney transplants. We further suggest that in sOTRs, a few ICI infusions could potentially be a cautious option, pending further evidence. Full article

Background: Over 60,000 patients are diagnosed annually with pancreatic cancer in the United States, most with pancreatic ductal adenocarcinoma (PDAC). Despite multimodality treatment, prognosis remains poor, underscoring the need to better define factors associated with improved survival in resectable disease. The aim of this study was to propose “completeness of therapy” in resectable PDAC based on chemotherapy type, relative dose intensity (RDI), duration, and timing of initiation, and to evaluate their association with overall survival (OS). Methods: A systematic review of PubMed identified 34 studies. Hazard ratios (HRs) were extracted and synthesized in forest plots. Outcomes focused on OS in relation to chemotherapy completion (cumulative cycles), time to adjuvant chemotherapy initiation (TTA), RDI, and regimen type. The goal was to conceptualize an evidence-based completeness-of-therapy framework for resected PDAC. Results: Completion of chemotherapy was associated with a 42% reduction in the hazard of death compared with incomplete therapy (HR = 0.58, 95% CI 0.47–0.71, p < 0.01). No significant OS difference was observed for longer TTA within a ≤12-week window after surgery (HR = 1.22, 95% CI 0.95–1.56, p = 0.10). Higher RDI demonstrated a large but non-significant trend toward improved OS (HR = 0.51, p = 0.24). Non-significant trends favoring gemcitabine-based regimens (HR = 0.87, p = 0.26) and FOLFIRINOX (HR = 0.79, p = 0.26) were observed, with FOLFIRINOX suggesting a 21% relative reduction in mortality. Conclusions: Chemotherapy completion is strongly associated with improved OS in resectable PDAC. Initiation of adjuvant therapy within 12 weeks appears sufficient, allowing recovery from surgery. Higher RDI and specific chemotherapy regimens demonstrated numerically favorable hazard ratios; however, these associations were not statistically significant and should be interpreted cautiously. Full article

Precision medicine in prostate cancer (PCa) is increasingly best understood as a continuum linking risk-adapted detection, multimodal diagnosis and phenotyping, and implementation-ready decision pathways. Contemporary clinical guidelines emphasize structured diagnostic strategies, appropriate use of advanced imaging, and selective deployment of biomarkers when results can alter management. Upstream risk enrichment using polygenic risk scores and multivariable prediction models may improve the yield of clinically significant disease while mitigating harms related to overdiagnosis. At the point of suspicion, magnetic resonance imaging-first pathways and reflex biomarker testing provide practical tools to reduce unnecessary biopsy while maintaining safeguards for the detection of clinically important disease. Beyond diagnosis, prostate-specific membrane antigen positron emission tomography refines disease-state phenotyping in initial staging, biochemical recurrence, and limited-burden presentations, while standardized acquisition and reporting improve reproducibility and multidisciplinary communication. Germline and tumor-based molecular profiling should be operationalized as a longitudinal care process with clear consent, turnaround targets, and test-to-action rules that define what each result enables at specific decision nodes. Finally, longitudinal monitoring approaches, including liquid biopsy and artificial intelligence-enabled pathology, are evolving rapidly and require transparent reporting and rigorous risk-of-bias appraisal before broad clinical adoption. This narrative review synthesizes key evidence across the precision continuum and outlines a decision-node-based, test-to-action framework for maximizing clinical benefit, maintaining quality, and ensuring equitable access. Full article

HER2DX is a 27-gene genomic assay generating three complementary scores: a pCR score predicting the likelihood of achieving pathological complete response (pCR, defined as absence of residual invasive disease after neoadjuvant therapy), a Risk score estimating long-term recurrence risk, and an ERBB2 mRNA score quantifying HER2 transcriptional activation. Together, these scores may guide treatment escalation or de-escalation strategies in routine practice. We performed a single-center observational study at 12 de Octubre University Hospital (Madrid, Spain), including patients with early-stage HER2-positive breast cancer who underwent HER2DX testing (2023–2025), and analyzed clinicopathologic features, treatment decisions, and pathological outcomes. Forty-five patients were included (median age 57 years). Stage II accounted for 71.1% of cases; 66.7% were hormone receptor-positive, and 31.3% were node-positive. HER2DX modified clinical management in 51.1% of patients. The pCR score changed the initial strategy (neoadjuvant therapy versus upfront surgery) in 17.8% of cases and, independently, favored de-escalation to taxane plus dual HER2 blockade, with 90% of high-score tumors achieving a pathological complete response. The Risk score informed chemotherapy backbone selection within stage II disease. The ERBB2 score correlated with HER2 immunohistochemical intensity. In this exploratory real-world cohort, HER2DX provided biologically distinct information beyond traditional immunohistochemistry and was associated with modifications in multidisciplinary treatment decision-making in early-stage HER2-positive breast cancer, warranting prospective validation in larger cohorts. Full article

There are a few molecules that are regularly used as markers for lymphatic endothelial cells (LECs) such as the adhesion molecule CD31/PEACAM1, the transcription factor PROX1, the Vascular Endothelial Growth Factor Receptor-3 (VEGFR3/FLT4), the glycoprotein podoplanin, and the hyaluronan receptor LYVE1. However, none of the molecules are exclusively expressed in LECs, and there is molecular and functional heterogeneity of LECs in initial lymphatics, lymphatic collectors and lymph nodes. Therefore, a combination of markers must be applied to identify lymphatics. This is particularly true for the characterization of conditions such as lymphatic malformations or cancers, in which the molecular profile of vessels may be variable or abnormal. Here we present two molecules that can help distinguish between endothelial cells of blood and lymphatic vessels: the scaffold protein liprin β-1 (PPFIBP1) and the intermediate filament synemin. We collected own data on the RNA and protein expression of the two molecules in humans, and studied publicly available databases. PPFIBP1 appears to be a suitable marker of LECs in initial lymphatics, collectors and lymph nodes, while synemin appears to be more restricted to initial lymphatics. We hope this will stimulate monoclonal antibody development and help expand the range of LEC markers in health and disease. Full article

Background: Cancer-associated thrombosis (CAT) is a leading cause of morbidity and mortality in cancer patients. Although international guidelines provide comprehensive recommendations for venous thromboembolism (VTE) prevention and treatment, the degree to which clinicians adhere to these guidelines in routine practice remains unclear, particularly in countries with limited national data such as Turkey. Methods: A cross-sectional, descriptive survey was conducted among oncology specialists (medical oncologists, radiation oncologists, and surgical oncologists) and cardiologists practicing across Turkey. A structured, case-based questionnaire comprising 21 multiple-choice questions was distributed electronically via SurveyMonkey. The questionnaire assessed perioperative VTE prophylaxis approaches, VTE risk assessment practices in ambulatory patients, primary and long-term secondary thromboprophylaxis preferences, acute VTE treatment strategies, and management of special clinical scenarios. Responses were analyzed using descriptive statistics and compared between oncologist and cardiologist groups. Results: A total of 84 physicians participated (34 oncologists [40.5%], 50 cardiologists [59.5%]). Perioperative and inpatient VTE prophylaxis practices were largely concordant with guideline recommendations, with 67.9% individualizing prophylaxis decisions and 66.7% initiating prophylaxis in hospitalized immobile patients when not contraindicated. However, only 33.7% routinely performed VTE risk assessment in ambulatory patients, and 64.6% did not use any validated risk scoring system. Low-molecular-weight heparin (LMWH) was the preferred agent for acute VTE treatment (72.6%), while direct oral anticoagulants (DOACs) gained preference in long-term secondary thromboprophylaxis (42.2%). No statistically significant differences were observed between oncologists and cardiologists across all survey items (all p > 0.05). Notably, 94.1% of respondents expressed a need to update their knowledge regarding CAT management. Conclusions: While oncologists and cardiologists in Turkey demonstrate general awareness of CAT guidelines, significant gaps persist in VTE risk stratification and primary prophylaxis for ambulatory cancer patients. The near-universal self-reported need for knowledge updates highlights the urgency for structured multidisciplinary education programs, integration of validated risk scoring tools into clinical workflows, and development of nationally adapted clinical practice guidelines. These findings reflect self-reported practices and may not fully represent actual clinical behavior; future studies incorporating medical record reviews or prescription data are needed to validate these observations. Full article

Sinonasal malignancies are rare, accounting for fewer than 3% of head and neck cancers, but their early presentation often overlaps with benign rhinosinusitis. Unilateral nasal obstruction, rhinorrhoea, facial pressure, and intermittent epistaxis may initially appear inflammatory, which contributes to diagnostic delay and late-stage presentation. Recent clinical guidance emphasizes that persistent unilateral symptoms, especially when accompanied by bleeding, focal endoscopic abnormalities, or orbital, dental, or neurologic features, should prompt specialist assessment rather than repeated empiric treatment. This commentary argues that the central clinical problem is not failure to recognize advanced disease, but failure to reconsider a benign working diagnosis when “sinusitis” stops behaving like sinusitis. This commentary proposes a pragmatic triage framework for unilateral or refractory sinonasal disease that prioritizes pattern recognition, focused nasal endoscopy, appropriate imaging, and timely biopsy where indicated. Its contribution is to connect three clinically relevant observations: sinonasal malignancy is rare and therefore easily deprioritized; unilateral, progressive, refractory, bleeding, orbital, dental, or neurologic features should prompt earlier cancer exclusion; and emerging AI-assisted endoscopy should currently be viewed only as a triage adjunct, not a substitute for imaging, histopathology, or multidisciplinary assessment. Full article

Aboriginal people in Western Australia (WA) experience poorer cancer outcomes compared to non-Aboriginal Australians, with significant disparities in cancer screening participation, later-stage diagnosis, and lower survival rates. This narrative review, informed by selected scoping methods, examined 69 peer-reviewed studies contributed by WA researchers from 2000 to 2024 to inform understanding of and address these inequities. Recurring issues requiring attention included promoting cultural safety in healthcare, addressing barriers to and disparities in cancer care, boosting cancer screening and awareness, enhancing education and communication, strengthening support systems and care navigation, improving treatment access and outcomes, and building workforce capacity. Recommendations to address the above challenges and improve cancer care and outcomes for Aboriginal people in WA included addressing barriers and disparities in cancer care; promoting effective education, communication, and culturally appropriate support; enhancing cancer screening participation and awareness initiatives; improving access to cancer treatment and outcomes; strengthening policy and system-level interventions; supporting families and communities throughout their cancer journey; building research capacity and data collection to guide Aboriginal and community-led initiatives. These recommendations highlighted that multi-level interventions are needed, from empowering Aboriginal people and strengthening communities to improving service delivery and driving systematic reforms. Overall, this narrative review informs future research, policy, and practice focused on equity to improve cancer outcomes for Aboriginal people in WA and beyond. Full article

Bone loss in the maxillofacial region arises from multiple causes, including periodontal disease, trauma, surgical procedures, infection, congenital anomalies, and cancer. Traditional treatment relies on bone grafting, either alone or in combination with biomaterials. Advances in tissue engineering have introduced synthetic or natural scaffolds to mimic the mineralized bone matrix. Natural scaffolds offer excellent biocompatibility and similarity to native tissue but often lack sufficient mechanical strength and exhibit poor degradation rates. Synthetic scaffolds provide tunable porosity and mechanical stability; however, their biological inertness makes them poor sources of osteogenic signaling. A key factor in the success of any scaffold is its interaction with the host immune system. Upon implantation, the innate immune response is initiated, with neutrophils and macrophages being the first cells to contact the scaffold. Macrophage polarization toward proinflammatory (M1) or anti-inflammatory (M2) phenotypes determines whether the microenvironment favors inflammation or remodeling. The adaptive immune response also plays a critical role: T and B lymphocytes may promote tolerance and integration through Th2/Treg pathways and antibody-mediated regulation, or they may trigger chronic inflammation and rejection through Th1/Th17 activation. This review examines the natural and synthetic materials used for bone remodeling and their biological properties. It then outlines the sequence of immune events occurring from the moment a scaffold is implanted to its potential integration or failure. Finally, this study highlights the relevance of cellular models and in vitro assays for the early evaluation of immunogenicity and biocompatibility, which are essential for optimizing scaffold design and improving outcomes in maxillofacial bone regeneration. Full article

Human cervical cancer and pre-cancer research relies on datasets scattered across modality-specific archives, imaging repositories, benchmark platforms, trial registries, and controlled-access catalogs. This fragmentation—combined with heterogeneous metadata, ambiguous use of “cervical” terminology, and inconsistent indexing of pre-cancer and screening/triage resources—limits reproducible discovery, access planning, and cross-modal benchmarking. We present the Cervical Cancer Dataset Catalog (CCDCAT), a machine-readable, versioned dataset of datasets that enumerates host-specific dataset-instance records anchored to stable identifiers and resolvable landing records within an explicitly declared discoverable source universe (U_v1.0) and a frozen discovery/labeling lexicon (Q_v1.0). The CCDCAT spans invasive cervical cancer, pre-cancer/dysplasia, and cervix-focused screening and triage phenotypes, and it covers molecular omics, imaging and microscopy (including cervix photography, cytology, and digital pathology), trial registry records, benchmark resources, and controlled-access catalogs represented as metadata with explicit access pathways. Eligibility and labels are assigned conservatively from source-provided metadata; when evidence is insufficient, the CCDCAT abstains rather than infers. In the initial release (CCDCAT-U_v1.0; v0.1), we enumerate 14 eligible dataset instances across 11 host systems within a declared universe of 21 sources. Releases include manuscript-ready tables and interoperable artifacts (schema, controlled vocabularies, provenance logs, abstention ledgers, and a queryable database), enabling reproducible filtering, linkage, and auditable reuse planning. Full article

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with chronic inflammation playing a central role in its pathogenesis. While established risk factors such as Helicobacter pylori (Hp), diet, and lifestyle are well recognized, growing epidemiological evidence links airborne particulate matter (PM) exposure with increased GC incidence and mortality. However, the biological mechanisms underlying this association remain poorly understood. This review integrates epidemiological evidence associating elevated PM exposure with GC risk and summarizes current mechanistic knowledge regarding PM gastric translocation and retention. The influence of PM size, chemical composition, and surface reactivity on biological activity is also discussed, highlighting the stomach as a plausible yet understudied target organ. Additionally, we compiled evidence from studies published between 2010 and 2026 demonstrating the ability of PM to induce inflammatory responses through activation of NF-κB, MAPK, JAK/STAT, and COX-2 signaling pathways across diverse biological systems. Although PM-induced inflammation has been extensively characterized in respiratory and other tissues, its contribution to gastric carcinogenesis remains largely unexplored. We propose that PM exposure may exacerbate Hp-driven inflammation, promoting a persistent pro-inflammatory microenvironment conducive to tumor initiation and progression. Collectively, these findings position PM as a biologically plausible and potentially modifiable risk factor for GC. Full article