Search Results (115,587)

Background/Objectives: Many patients with breast cancer are treated with chemotherapy, including taxanes. These regimens bear a significant risk of potentially burdensome peripheral neuropathy. A scoring system supported by a neuropathy tracker, which can be self-administered by the patients, likely facilitates and speeds up the diagnosis of chemotherapy-induced peripheral neuropathy (CIPN). Before such a scoring system can be used, determination of the optimal cut-off score to discriminate between CIPN and no CIPN is necessary. The prospective NEURO-BREAC trial (NCT07148336) aims to identify the optimal cut-off score in patients treated with chemotherapy and adjuvant irradiation for breast cancer. Methods: The main goal of the NEURO-BREAC trial is to provide the optimal cut-off of a scoring system to discriminate between moderate to severe CIPN and no CIPN in breast cancer survivors previously treated with paclitaxel- or docetaxel-based chemotherapy and irradiation. The scores (0 to 44 points) are obtained by using a neuropathy tracker. This tracker is based on self-evaluation of symptoms and signs of CIPN by study participants. In addition, satisfaction of the patients with the scoring system is assessed. Twenty-four patients (sixteen patients with moderate to severe CIPN and eight patients without CIPN) are required for the Full Analysis Set. Assuming that about 5% of patients will not qualify for this set, 26 patients should be recruited for the NEURO-BREAC trial. The results of this trial are considered an important step for the development of a scoring system contributing to the identification of CIPN in breast cancer patients. Full article

Background: The unfolded protein response (UPR) is an evolutionarily conserved, synchronized, and orchestrated process triggered by eukaryotic cells in response to endoplasmic reticulum (ER) stress. UPR restores the ER’s capacity to handle large protein loads within it, and still fold and process these proteins accurately. Many recent studies have documented the non-canonical roles of the UPR, outside of protein quality control, in the context of lipid metabolism and the immune system in cancer. Cancer cells have been known to hijack the UPR to promote survival and evade immune surveillance. However, the underlying mechanisms remain poorly understood. Objectives: Here, we critically summarize canonical and non-canonical UPR mechanisms in the contexts of tumor immune microenvironment and lipid metabolism, dissect their crosstalk with other cell fate signaling pathways within cancer, and propose therapeutic strategies to exploit this relationship. We also discuss the fundamental challenges of solely targeting UPR and emphasize the importance of patient stratification, biomarker development, and rational combination therapies to maximize the potential for therapeutic gain. We provide a deconvoluted mechanistic understanding of the UPR process in an attempt to spark prospective clinically relevant therapeutics research. Full article

Background: The combination of multi-omics data, including genomics, transcriptomics, and epigenomics, with medical imaging modalities (PET, CT, MRI, histopathology) has emerged in recent years as a promising direction for the advancement of precision oncology. Many researchers have contributed to this domain, exploring the multi-modality aspect of using both multi-omics and image data for better cancer identification, subtype classifications, cancer prognosis, etc. Methods: We present an umbrella review summarizing the state of the art in fusing imaging modalities with omics and artificial intelligence, focusing on existing reviews and meta-analyses. The analysis highlights early, late, and hybrid fusion strategies and their advantages and disadvantages, mainly in tumor classification, prognosis, and treatment prediction. We searched review articles until 25 May 2025 across multiple databases following PRISMA guidelines, with registration on PROSPERO (CRD420251062147). Results: After identifying 56 articles from different databases (i.e., PubMed, Scopus, Web of Science and Dimensions.ai), 35 articles were screened out based on the inclusion and exclusion criteria, keeping 21 studies for the umbrella review. Discussion: We investigated prominent fusion techniques in various contexts of cancer types and the role of machine learning in model performance enhancement. We address the problems of model generalizability versus interpretability within the clinical context and argue how these multi-modal issues can facilitate translating research into actual clinical scenarios. Conclusions: Lastly, we recommend future work to define clearer and more reliable validation criteria, address the need for integration of human clinicians with the AI system, and describe the trust issue with AI in cancer care, which requires more standardized approaches. Full article

Ritonavir (RTV), an effective aspartyl protease inhibitor, was originally developed to counter the replication of human immune deficiency virus and then employed as a pharmacokinetic enhancer in antiretroviral therapy. Yet unexpectedly, RTV exerted antitumor effects that added to its antiviral action, as it impacted the migration, invasion, oxidative stress, and proteasome function of human tumor cells. More recently, RTV was shown to directly inhibit DNA repair enzymes, thereby enhancing radiosensitivity and synergizing with chemotherapeutics across multiple cancer models. However, RTV induced oxidative stress and DNA damage also in non-tumor cells, including the reproductive ones. This duality highlights both the possibility of RTV anticancer use and the concern for its safety. In this Perspective, we propose the repurposing of RTV as a novel tool to potentiate DNA-damage-based antitumor therapies such as radiotherapy and/or chemotherapy. At the same time, we underscore the need for a careful assessment of RTV side effects. Full article

Colorectal cancer (CRC) is the leading cause of cancer-related death in Puerto Rico, a U.S. territory with noted disparities in CRC incidence, particularly among those with early-onset disease (EOCRC). Although EOCRC incidence has been consistently increasing in the U.S. mainland, and a disparate burden has been reported among Hispanics, EOCRC mortality and survival are yet to be assessed among Hispanics living in Puerto Rico (PRH). In this study, we analyzed EOCRC mortality and survival trends in PRH and compared these to those of other U.S. populations. Mortality data were obtained from the Puerto Rico Central Cancer Registry and the Surveillance, Epidemiology, and End Results (SEER) program. Descriptive characteristics and temporal trends were derived via SEER*Stat software (version 9.0.42) and Joinpoint regression models, respectively. Relative survival was estimated using the Actuarial method and the Ederer II approach. Overall, CRC mortality trends showed a decline, but an increase in EOCRC mortality among Hispanics. PRH exhibited the lowest 5-year survival in regional cancers (54.10%), with NHB having the lowest survival among younger individuals. This study highlights significant disparities in EOCRC mortality trends and underscores an urgent need for targeted public health strategies and research efforts to address the disproportionate burden of EOCRC among PRH. Full article

Breast cancer rarely metastasizes to the parotid gland. Early recognition in patients with a history of malignancy is critical for timely diagnosis and treatment. We report the case of a 60-year-old female who presented with a two-month history of a left periauricular mass, 18 months after completing treatment for breast carcinoma. Despite the patient’s oncologic history, initial evaluation by our maxillofacial surgery service showed no evidence of distant metastasis, and we initially ruled out metastatic disease. Clinical evaluation, contrast-enhanced computed tomography (CT), fine-needle aspiration cytology (FNAC), PET-CT, and histopathological analysis were performed. Given the persistent and progressive nature of the mass, surgical excision was undertaken to obtain a definitive diagnosis and provide local control. Immunohistochemical analysis of the resected mass and adjacent node confirmed metastatic breast carcinoma infiltrating the parotid parenchyma and an intra-parotid lymph node, with strong positivity for progesterone receptor (PR) and carcinoembryonic antigen (CEA). Unfortunately, several months later, the patient developed pulmonary metastases and subsequently died. Full article

Among the gynecological cancers, ovarian cancer is the most fatal. Despite advancements in modern medicine, the survival rate is abysmally low among ovarian cancer patients. Ovarian cancer poses several unique challenges, like late diagnosis due to the initial vagueness of the symptoms and lack of effective screening protocols. Recently, biomaterials have been explored and utilized extensively for the diagnosis, treatment, and screening of ovarian malignancies. Biomaterials can help bypass the obstacles of traditional chemotherapy and enhance imaging capabilities. They are also indispensable for next-generation biosensors and tumor organoids. Biomaterials inspired by biomimetic strategies that replicate the structural, chemical, and functional properties of natural biological systems have proven to have better functionalities. While numerous review articles have examined biomaterials in oncology, there is a lack of reviews dedicated specifically to their applications in ovarian cancer. This review aims to address this critical gap by providing the first comprehensive overview of the current biomaterial research on ovarian cancer and highlighting key challenges, opportunities, and future directions in this evolving interdisciplinary field. Full article

The convergence of nanotechnology and bioaerogels has paved the way for the development of multimodal nanostructured bioaerogels with remarkable potential in smart drug delivery systems. These advanced biomaterials integrate multiple functionalities, including sensing, targeting, and therapeutic actions, to enhance drug efficacy, minimize systemic side effects, and enable real-time monitoring of therapeutic responses. This review provides a comprehensive analysis of the structural design, physicochemical properties, and fabrication strategies of multimodal bioaerogels. It further explores their role in responsive drug delivery, emphasizing stimuli-responsive mechanisms such as pH, temperature, and enzymatic triggers. The incorporation of nanomaterials, including metallic nanoparticles, carbon-based nanostructures, and polymeric nanocarriers, has endowed bioaerogels with tunable porosity, controlled drug release, and bioactive functionalities. Additionally, their application in precision medicine, particularly for cancer therapy, antimicrobial treatments, and tissue engineering, is critically examined. Challenges related to scalability, biocompatibility, and regulatory compliance are also discussed, alongside future perspectives on advancing these bioaerogels toward clinical translation. By integrating interdisciplinary insights, this review underscores the transformative potential of multimodal nanostructured bioaerogels in the next generation of intelligent drug delivery systems. Full article

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet their benefits remain limited to a subset of patients, underscoring the need for more reliable biomarkers and novel therapeutic strategies. The gut microbiome has emerged as a critical modulator of systemic immunity and a promising determinant of ICI response. Evidence links specific microbial features, taxa, and bioactive metabolites to enhanced antitumor immunity, whereas disruptions, such as antibiotic exposure, are associated with poorer outcomes. Advances in sequencing and multi-omics technologies have provided more profound insights into microbiome-immune crosstalk, though methodological heterogeneity continues to challenge reproducibility. Translational studies demonstrate that microbiome-based intervention, including fecal microbiota transplantation (FMT), biotics supplementation, and engineered microbial strains, can enhance ICI efficacy or mitigate immune-related toxicities. Despite encouraging early clinical signals, broader implementation requires methodological rigor, standardized protocols, and innovative trial designs that account for host and environmental factors. For clinicians, the most immediate strategies involve prudent antibiotic stewardship and patient enrollment in microbiome-focused clinical trials. Overall, the gut microbiome is a promising biomarker and a therapeutic target, representing a new frontier for personalizing immunotherapy and improving patient outcomes in oncology. Full article

Deuterium, a stable isotope of hydrogen present in natural water at ~150 ppm, has been implicated in modulating cellular metabolism and tumor progression. While deuterium-depleted water (DDW) has shown anti-cancer effects in preclinical and clinical studies, the underlying transcriptional mechanisms remain incompletely defined. Here, we profiled gene expression in A549 lung adenocarcinoma cells cultured for 72 h in media containing four graded deuterium concentrations (40, 80, 150, and 300 ppm) using a targeted NanoString panel of 236 cancer-related genes. After stringent quality filtering, 87 genes were retained and classified into nine distinct expression patterns based on fold-change trends relative to the 150 ppm control. High deuterium (300 ppm) induced strong upregulation (up to 2.1-fold) of oncogenic and survival-related genes (e.g., EGFR, CTNNB1, STAT3, CD44), while DDW (40–80 ppm) led to selective downregulation (down to 0.58-fold) of oncogenes (e.g., MYCN, ETS2, IRF1) and drug-resistance genes (e.g., ABCB1). Se-veral genes involved in DNA repair, apoptosis, and extracellular matrix remodeling exhibited dose-dependent responses, suggesting coordinated regulation by deuterium abundance. These findings demonstrate that deuterium concentration functions as a biologically active variable capable of modulating cancer-relevant gene networks. This exploratory dataset refines mechanistic models of DDW action and provides a foundation for future studies incorporating biological replication, functional assays, and in vivo validation. Significance: Deuterium concentration modulation alters oncogenic, apoptotic, and drug-resistance gene networks in lung adenocarcinoma cells, refining prior models of deuterium-depleted water effects. These findings identify deuterium concentration as a biologically active variable warranting further mechanistic and translational investigation. Full article

Background: Breast cancer (BC) is the most common malignancy among women, and genetic predisposition plays a critical role in its development. Among DNA mismatch repair (MMR) genes, MLH1 is essential for maintaining genomic stability, and promoter variants may influence its transcriptional regulation. Variants in MMR genes, including MLH1, have been implicated in cancer susceptibility; however, evidence regarding the promoter polymorphism −93G>A (rs1800734) and its association with BC remains limited and inconsistent across populations. Methods: We conducted a case–control study of 143 breast cancer patients and 161 cancer-free controls of Azerbaijani origin. Genotyping of MLH1 −93G>A was performed using PCR-RFLP and validated by next-generation sequencing (NGS). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under different genetic models by logistic regression, followed by false discovery rate (FDR) correction for multiple testing. Results: The genotype distribution among patients was 25.9% GG, 58.7% GA, and 15.4% AA, compared with 37.9%, 46.6%, and 15.5% in controls. A significant association was observed between the GA genotype and BC risk (OR = 1.855, 95% CI: 1.104–3.085, p = 0.019). In the dominant model (GA + AA vs. GG), carriers of the A allele showed increased breast cancer risk (OR = 1.747, 95% CI: 1.069–2.856, p = 0.026). Genotype distribution was also associated with tumor grade (p = 0.047) and stage (p = 0.013). However, none of the associations remained significant after FDR adjustment. Conclusions: This pilot study provides the first evidence from Azerbaijan suggesting a potential role of the MLH1 −93G>A variant in breast cancer susceptibility. Although the associations were nominal and require validation in larger cohorts, the findings point to a biologically plausible link between MLH1 promoter variation and impaired MMR activity, which may contribute to polygenic breast cancer risk. These preliminary results emphasize the importance of evaluating MMR gene variants in underrepresented populations and support further studies integrating functional assays and broader gene coverage. Full article

Endometrial cancers increase expression of the renin–angiotensin system (RAS). This study aimed to determine if inhibiting the RAS would reduce the viability and proliferation of endometrial cancer cells. The expression of RAS genes was measured in three endometrial epithelial adenocarcinoma cell lines (Ishikawa, HEC-1-A, AN3CA). Ishikawa cells had the highest expression of REN, ACE, and AGTR1 mRNA. AGT mRNA and protein levels were most abundant in HEC-1-A cells. We then determined the effects of drugs that inhibit the action of renin (VTP-27999 and aliskiren) or angiotensin-converting enzyme (perindoprilat) or block the angiotensin II type 1 receptor (losartan and telmisartan). Overall, VTP-27999, aliskiren, perindoprilat, and losartan had minimal effects on cell viability in all three cell lines, and combinations of these drugs did not have any effect. Telmisartan (a dual angiotensin receptor blocker and PPAR-γ agonist) significantly reduced the viability of all three cell lines and reduced the proliferation of both Ishikawa and AN3CA cells. Telmisartan was more effective than troglitazone (PPAR-γ agonist) in Ishikawa and HEC-1-A cells. RAS inhibitors were most effective in Ishikawa cells, which had the highest levels of RAS expression. Therefore, levels of RAS expression in endometrial cancers might indicate the potential efficacy of RAS drugs. Full article

Nature has long served as a prolific source of bioactive compounds, offering structurally diverse scaffolds for the development of therapeutics. In recent years, increasing attention has been given to nature-inspired covalent inhibitors, molecules that form covalent bonds with pathogen- or cancer-specific targets, due to their potential selectivity and sustained biological activity. This review explores the landscape of covalent inhibitors derived from natural sources, with a focus on compounds from fungi, marine organisms, bacteria and plants. In particular, emphasis is placed on the molecular mechanisms through which these compounds exert their activity against different types of pathogens and other biomedically relevant targets, highlighting key structural motifs that facilitate covalent interactions. Furthermore, the review discusses recent advances in synthetic modification, target identification, and optimization strategies that bridge natural compound discovery with modern drug development. By drawing insights from nature’s chemical repertoire, this work ultimately displays the potential of natural covalent inhibitors as a promising foundation for next-generation anti-infective and anticancer therapeutics. Full article

Polo-like kinase 1 (PLK1) is a serine/threonine kinase that orchestrates multiple critical events during mitosis, including centrosome maturation, spindle assembly, kinetochore–microtubule attachment, and cytokinesis. Dysregulation and overexpression of PLK1 are frequently observed in various cancers, correlating with increased proliferation, metastatic potential, and poor prognosis, which highlights its potential as a therapeutic target. Traditional small-molecule inhibitors have predominantly focused on the ATP-binding site of the N-terminal kinase domain, effectively inducing mitotic arrest and apoptosis in tumor cells; however, these compounds often suffer from limited selectivity and off-target toxicity. The C-terminal Polo-box domain (PBD), responsible for substrate recognition and subcellular localization, has emerged as an alternative and highly selective target for inhibitor design, enabling the disruption of protein–protein interactions critical for PLK1 function. Here, we present a comprehensive review demonstrating the potential inhibition of several compounds against PLK1. This work establishes a foundation for future preclinical development of small molecule-based therapeutics against PLK1-dependent malignancies. Full article

Mg-based alloys are one of the most promising materials used in regenerative medicine for bone tissue engineering. Considering the increasing prevalence of a continuously aging population, as well as the high incidence of accidents and bone cancers, it is crucial to explore biomaterials that can serve as bone substitutes. After carefully analyzing the literature in the introduction section, we proposed two Mg-based alloys as suitable for obtaining biodegradable structures for bone defect treatment. To achieve trustworthy results, the alloys’ microstructure was investigated using microscopic techniques coupled with energy-dispersive spectroscopy and X-ray diffraction. The obtained results were comparable with those described in references on similar Mg alloys. Then, the mechanical compression properties were highlighted, and the in vitro corrosion behavior proved that Mg-Zn exhibited a reduced corrosion rate compared to the Mg-Nd alloy, as tested using electrochemical methods. However, the in vivo tests showed good biocompatibility for both magnesium alloys. In conclusion, both alloys are suitable for use as potential bone substitute applications, but it must be taken into consideration that Mg-Zn alloys present lower biodegradation and mechanical properties. For future investigations, we aim to develop bone substitutes made from these materials, specifically designed for small bone defect treatment and with patient-adapted geometry. Due to the differences mentioned above, various designs will be tested. Full article