Search Results (66)

Precision oncology, also known as personalized oncology or precision medicine, is the tailoring of cancer treatment to individual patients based on the specific genetic, molecular, and other unique characteristics of their tumor. The goal of precision oncology is to optimize the effectiveness of cancer treatment while minimizing toxicities and improving patient outcomes. Precision oncology recognizes that cancer is a highly heterogeneous disease and that each patient’s tumor has a distinct genetic diversity. Precision medicine individualizes therapy by using information from a patient’s tumor in the context of clinical history to determine optimal therapeutic approaches and increasing numbers of drugs target specific tumor alterations. Several targeted therapies with approved companion diagnostics are commercially available, the haves of precision oncology, where predictive biomarkers guide clinical decision-making and improve outcomes. However, many therapies still lack clear biomarkers, the have nots, posing a challenge to fully realizing the promise of precision oncology. Herein, we describe the current state of the art for breast cancer precision oncology and highlight the therapeutic agents that require a more robust biomarker. Full article

Chronic inflammatory enteropathies (CIEs) in companion animals represent a group of idiopathic, immune-mediated gastrointestinal disorders in which the intestinal epithelium can be altered, affecting intestinal functionality, nutrient absorption, and microbiota composition. This review presents an overview of markers that could be used for the assessment of intestinal health, focusing extensively on functional biomarkers, with particular attention to fatty acids (including short-chain fatty acids, SCFAs) and amino acids. Studies have consistently shown reduced concentrations of SCFAs in companion animals with CIEs compared to healthy groups. These alterations occur with varying intensity depending on the type of enteropathy. Alterations in saturated, monounsaturated, and long-chain polyunsaturated fatty acids have also been reported in blood and feces, particularly in omega-3 and omega-6 derivatives, as well as in the elongase and desaturase indices responsible for endogenous synthesis. In addition, amino acids serve as precursors to key metabolites involved in mucosal immunity, oxidative stress regulation, and microbial homeostasis. In CIEs, alterations in systemic and fecal amino acid profiles have been observed, reflecting both host metabolic adaptation and microbial dysbiosis. Integrating fatty acid and amino acid profiles can help distinguish different types of enteropathies, providing additional discriminatory power for determining response to dietary treatment. Future research should aim to elucidate the causal relationships between metabolic alterations and disease pathogenesis, which could lead to novel dietary interventions targeting metabolic interactions between the microbiota and the host. Full article

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in diagnosis, prevention, and treatment. Predictive biomarkers offer the potential to revolutionize clinical management, particularly in the preoperative setting, but their implementation requires careful consideration of ethical implications. This scoping review analyzes the ethical landscape of using immunohistochemistry (IHC) for molecular subtyping in PDAC, focusing on its utility, accessibility, and potential impact on patient care. We conducted a systematic literature search in the PubMed, Scopus and Google Scholar databases (2015–2025) using COVIDENCE, which identified 130 references. Of these, 79 were reviewed in a full-text format, and 9 ultimately met the inclusion criteria for our analysis. IHC offers several advantages as a companion diagnostic tool. It is relatively inexpensive, widely available in most pathology laboratories, and can be readily integrated into existing clinical workflows. This contrasts with more complex molecular subtyping methods, such as gene expression profiling, which can be costly, require specialized equipment and expertise, and may not be readily accessible in all clinical settings. Furthermore, accurate analysis of gene expression requires the localized targeting of individual cells; therefore, digesting the sample for bulk analysis would be less informative than using spatial localization techniques such as IHC. Because biomarker regulation can occur at the level of transcription or translation, protein-level assessment via IHC is often more accurate than mRNA analysis. Standardized IHC protocols for biomarker assessment are therefore essential for translating the molecular subtyping of PDAC into clinically actionable treatment strategies, especially for aggressive subtypes like basal-like tumors. This readily deployable IHC-based approach can optimize therapy selection, maximizing patient benefits and minimizing exposure to ineffective and potentially toxic treatments. This review critically analyzes the ethical dimensions of this method, grounded in the principles of autonomy, beneficence, non-maleficence, and justice. The review urges the medical community to fully utilize the potential of IHC-driven molecular subtyping to improve outcomes in PDAC, while ensuring equitable and responsible access to the benefits of precision oncology for all patients. Full article

The importance of lipid molecules present at the level of cell membranes is already well known. They can act as secondary messengers, participating in signal transduction processes that regulate various organ functions; furthermore, their nature significantly influences cellular properties and functions. Recent studies have seen how the lipid composition of cell membranes is connected to the animal lifespan and the onset of several pathological conditions. While numerous studies have been conducted aimed at characterizing the membrane lipidomic profile in the human field, in the animal field, especially in pets, the number of studies is very limited. In recent years, preliminary analyses have been conducted to provide initial information on the composition of membrane fatty acids in healthy pets and those with chronic enteropathy. The results of these studies are very interesting as they highlight differences in fatty acid composition between the two groups of animals. Obviously, a greater number of works is needed to obtain more reliable results and to analyze how the membrane lipid composition can vary in different breeds and sizes of dogs and cats in an attempt to understand the mechanisms underlying it. The present review is divided into three main parts: the first one examines the close influence of fatty acids on membrane properties/functions, the second one presents the main lipidomic analyses conducted so far on companion animals, and the third and final part summarizes the latest works on the link between membrane lipid profiles and animal lifespans, also focusing on dietary and non-dietary strategies able to influence it. Membrane lipidomics allows us to obtain a concrete overview of an animal’s metabolism and nutrition; furthermore, lipid alterations could be used as biomarkers for the early diagnosis of pathologies. This represents an innovative tool in the veterinary field to monitor the metabolic/health status of animals. Full article

This experiment aimed to assess the effects of both preweaning nutrition and postweaning growth rate on the resilience of dairy heifers from birth to 20 months of age. Immune competence and metabolic characteristics were assessed via repeated vaccine immune challenges throughout early life. Heifers were subject to either a high or low preweaning nutritional treatment (high: 8 L vs. low: 4 L of milk per day). Calves in these treatment groups were then equally divided into either a high or low postweaning growth rate treatment until 20 months of age. Nutritional intake, growth and metabolic data can be found in a companion paper, while the current paper outlines the responses to the three immune challenges. In the preweaning phase, heifers on a high milk volume had superior immune competence, demonstrated by higher monocyte and eosinophil counts. All other immune biomarkers were not different between treatments. By 8 months of age, the differences in monocytes were lost; however, the differences in preweaning eosinophil counts remained at 8 months and through to 13 months of age. At 13 months of age, there were also three-way interaction effects of preweaning nutrition, postweaning growth rate and vaccination for white blood cell count and neutrophil count; however, the trends in these responses appear random and do not align towards any clear advantages of pre- or postweaning nutrition. Metabolic responses to the immune challenges do not suggest any form of carryover effect from the preweaning phase and seemed to reflect the nutritional input at the time. Full article

Recent advancements in molecular biology have led to the discovery of potential biomarkers for the diagnosis of acute kidney disease (AKD) and chronic kidney disease (CKD). The use of multiple biomarkers in the diagnosis of kidney disease has the potential to enhance both specificity and sensitivity, enabling early detection and intervention that could ultimately reduce morbidity and mortality rates. This review provides an overview of studies on urine and blood biomarkers and examines their utility and significance in various clinical settings. Further and continuous research is needed to support the application of these biomarkers in clinical practice to facilitate early diagnosis, guidance for different interventions, and the monitoring of disease progression. Full article

Polymerase chain reaction (PCR) chips are advanced, microfluidic platforms that have revolutionized biomarker discovery and validation because of their high sensitivity, specificity, and throughput levels. These chips miniaturize traditional PCR processes for the speed and precision of nucleic acid biomarker detection relevant to advancing drug development. Biomarkers, which are useful in helping to explain disease mechanisms, patient stratification, and therapeutic monitoring, are hard to identify and validate due to the complexity of biological systems and the limitations of traditional techniques. The challenges to which PCR chips respond include high-throughput capabilities coupled with real-time quantitative analysis, enabling researchers to identify novel biomarkers with greater accuracy and reproducibility. More recent design improvements of PCR chips have further expanded their functionality to also include digital and multiplex PCR technologies. Digital PCR chips are ideal for quantifying rare biomarkers, which is essential in oncology and infectious disease research. In contrast, multiplex PCR chips enable simultaneous analysis of multiple targets, therefore simplifying biomarker validation. Furthermore, single-cell PCR chips have made it possible to detect biomarkers at unprecedented resolution, hence revealing heterogeneity within cell populations. PCR chips are transforming drug development, enabling target identification, patient stratification, and therapeutic efficacy assessment. They play a major role in the development of companion diagnostics and, therefore, pave the way for personalized medicine, ensuring that the right patient receives the right treatment. While this tremendously promising technology has exhibited many challenges regarding its scalability, integration with other omics technologies, and conformity with regulatory requirements, many still prevail. Future breakthroughs in chip manufacturing, the integration of artificial intelligence, and multi-omics applications will further expand PCR chip capabilities. PCR chips will not only be important for the acceleration of drug discovery and development but also in raising the bar in improving patient outcomes and, hence, global health care as these technologies continue to mature. Full article

Background: New safety concerns about targeted anticancer agents (TAAs) often emerge in the first few years after their initial regulatory approval. Our aim was to determine whether new serious and potentially fatal adverse drug reactions (ADRs) continue to emerge in the updated drug labels of TAAs several years after their initial regulatory approval and whether their emergence can be predicted. Methods: The updated drug labels of TAAs approved by the U.S. Food and Drug Administration before July 2013 were analyzed. Serious and potentially fatal ADRs were identified in the Warnings & Precautions (WPs) and Boxed Warnings (BWs) sections of the updated drug labels. Generalized linear mixed models were used to examine the associations between the number of adverse drug reactions and time, drug type (small molecules vs. monoclonal antibodies), and the availability of companion diagnostics for biomarkers. Results: Among 37 eligible TAAs, 25 (68%) were small molecules and 11 (30%) had available companion diagnostics for the biomarkers. Time was a significant predictor of new WPs (p ˂ 0.001) and BWs (p = 0.008). The updated drug labels of the small molecules received significantly more new WPs (p = 0.042) as compared to monoclonal antibodies. The availability of the companion diagnostics for the biomarkers did not have an impact on the emergence of new ADRs. Conclusions: New serious ADRs of TAAs continue to emerge in updated drug labels several years after their initial regulatory approval. Oncologists, regulators, and payers should be aware of the changing risk–benefit ratios of approved TAAs. Full article

Cancer is a leading cause of death among companion animals, with many cases diagnosed at advanced stages when clinical signs have appeared, and prognosis is poor. Emerging diagnostic technologies, including Artificial Intelligence (AI)-enhanced imaging, liquid biopsies, molecular diagnostics, and nematode-based screening, can improve early detection capabilities in veterinary medicine. These tools offer non-invasive or minimally invasive methods to facilitate earlier detection and treatment planning, addressing the limitations of traditional diagnostics, such as radiography and tissue biopsies. Recent advancements in comparative oncology, which leverage the biological similarities between human and companion animal cancers, underscore their translational value in improving outcomes across species. Technological advances in genomics, bioinformatics, and machine learning are driving a shift toward precision medicine, enabling earlier detection, personalized treatments, and monitoring of disease progression. Liquid biopsy testing detects circulating tumor DNA and tumor cells, providing actionable insights into tumor genetics without invasive procedures. Imaging systems enhance diagnostic precision, offering consistent and accurate tumor identification across veterinary practices, while portable innovations like Caenorhabditis elegans-based screening provide accessible options for underserved regions. As these technologies migrate from human medicine to veterinary applications, they are poised to redefine cancer care for companion animals. This review highlights key advancements in diagnostic technologies and their application in veterinary oncology, with a focus on enhancing early detection, accessibility, and precision in cancer care. By fostering the adoption of these innovations, veterinary oncology can achieve a new standard of care, improving outcomes for both animals and humans through the lens of comparative oncology. Full article

Postbiotics are emerging as potential functional ingredients for companion animal diets. This study aimed to determine if a Saccharomyces cerevisiae-based postbiotic can alter cytokine and stress responses to exercise and transport stress in adult Labrador Retrievers. Dogs received 15 g ground corn germ (Control, n = 12), 7.5 g postbiotic (Low, n = 12), or 15 g postbiotic (High, n = 12), daily for 63 days. Exercise was twice weekly for 7 weeks, and a single transport per dog occurred in week 8. Fecal inflammatory biomarkers, serum chemistries, and complete blood counts were assessed at the beginning and end of the study. Serum cytokines were quantified before and 18–20 h after the first and last exercise runs. Gait analysis was assessed before and 24 h after the first and final runs. Saliva cortisol was measured before and after transportation. Treatment did not affect blood chemistries, gait, fecal biomarkers, or saliva cortisol (p ≥ 0.19). Eosinophils increased slightly in Controls (p = 0.01), though remained below 0.80 × 10⁹ cells/L. Most cytokines were unaffected by treatment (p ≥ 0.15), but there were minor changes in circulating monocyte chemoattractant protein-1 (p = 0.01) and IL-8 over time at the initial run (p = 0.03) and IL-10 in males (p = 0.02) in the Low dose dogs. The High dose decreased Blautia (p = 0.04) slightly and tended to decrease Fusobacterium abundances (p = 0.07). The Low dose tended to increase Clostridium hiranonis (p = 0.07) slightly. The tested S. cerevisiae postbiotic produced small changes in immune function and gut microbial species in dogs. Full article

The use of companion diagnostics has become a standard in precision oncology in the context of ongoing therapeutic innovation. However, certain limitations make their application imperfect in current practice. This position paper underscores the need to broaden the notion of companion testing, considering the potential of emerging technologies, including computational biology, to overcome these limitations. This wave of progress should impact not only our representation of the analytical tool itself but also the nature of the tumoral sample under analysis (liquid biopsies). The complex inter-relationship between companion test guided-personalized therapy, and health agency policies for new drug agreements will also be discussed. Full article

Abiraterone acetate (AA) serves as a medication for managing persistent testosterone production in patients with metastatic castration-resistant prostate cancer (mCRPC). However, its efficacy varies among individuals; thus, the identification of biomarkers to predict and follow treatment response is required. In this pilot study, we explored the potential of circulating microRNAs (c-miRNAs) to stratify patients based on their responsiveness to AA. We conducted an analysis of plasma samples obtained from a cohort of 33 mCRPC patients before and after three, six, and nine months of AA treatment. Using miRNA RT-qPCR panels for candidate discovery and TaqMan RT-qPCR for validation, we identified promising miRNA signatures. Our investigation indicated that a signature based on miR-103a-3p and miR-378a-5p effectively discriminates between non-responder and responder patients, while also following the drug’s efficacy over time. Additionally, through in silico analysis, we identified target genes and transcription factors of the two miRNAs, including PTEN and HOXB13, which are known to play roles in AA resistance in mCRPC. In summary, our study highlights two c-miRNAs as potential companion diagnostics of AA in mCRPC patients, offering novel insights for informed decision-making in the treatment of mCRPC. Full article

Background: Mental health disorders are the number one cause of maternal mortality and a significant maternal morbidity. This scoping review sought to understand the associations between social context and experiences during pregnancy and birth, biological indicators of stress and weathering, and perinatal mood and anxiety disorders (PMADs). Methods: A scoping review was performed using PRISMA-ScR guidance and JBI scoping review methodology. The search was conducted in OVID Medline and Embase. Results: This review identified 74 eligible English-language peer-reviewed original research articles. A majority of studies reported significant associations between social context, negative and stressful experiences in the prenatal period, and a higher incidence of diagnosis and symptoms of PMADs. Included studies reported significant associations between postpartum depression and prenatal stressors (n = 17), socioeconomic disadvantage (n = 14), negative birth experiences (n = 9), obstetric violence (n = 3), and mistreatment by maternity care providers (n = 3). Birth-related post-traumatic stress disorder (PTSD) was positively associated with negative birth experiences (n = 11), obstetric violence (n = 1), mistreatment by the maternity care team (n = 1), socioeconomic disadvantage (n = 2), and prenatal stress (n = 1); and inverse association with supportiveness of the maternity care team (n = 5) and presence of a birth companion or doula (n = 4). Postpartum anxiety was significantly associated with negative birth experiences (n = 2) and prenatal stress (n = 3). Findings related to associations between biomarkers of stress and weathering, perinatal exposures, and PMADs (n = 14) had mixed significance. Conclusions: Postpartum mental health outcomes are linked with the prenatal social context and interactions with the maternity care team during pregnancy and birth. Respectful maternity care has the potential to reduce adverse postpartum mental health outcomes, especially for persons affected by systemic oppression. Full article

Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it is estimated that the effect of the HPV vaccine will not be reflected in HNSCC prevalence until 2060. Efforts have begun to decrease morbidity of standard therapies for this disease, and its improved characterization is being leveraged to identify and target molecular vulnerabilities. Companion biomarkers for new therapies will identify responsive tumors. A more basic understanding of two mechanisms of HPV carcinogenesis in the head and neck has identified subtypes of HPV+ HNSCC that correlate with different carcinogenic programs and that identify tumors with good or poor prognosis. Current development of biomarkers that reliably identify these two subtypes, as well as biomarkers that can detect recurrent disease at an earlier time, will have immediate clinical application. Full article

Background: Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check this finding in our setting. Methods: A cross-sectional observational study (n: 572 psoriasis patients, 30% with PsA) was conducted. Different study variables were collected in detail, as well as classic cardiometabolic risk factors. The distribution of the HLA-Cw6 allele and the IFIH1/MDA5 gene variants previously linked to disease risk were determined in the study cohort and stratified according to the cardiometabolic comorbidity. Linear and logistic regression models were constructed to analyze these associations. Results: The study cohort included 309 men and 263 women, with a mean age of 46.7 years (SD 14.5) and a mean disease duration of 19.4 years (SD 14.8). We confirmed the known association between HLA-Cw6 and type I psoriasis (familial, severe, and early onset). Psoriasis severity (OR: 2.14), female sex (OR: 1.63), and the IFIH1/MDA5 rs1990760 TT genotype (OR: 1.62) were significantly related to PsA, while HLA-Cw6 was protective (OR: 0.65). HLA-Cw6 carriers showed a lower waist perimeter, lower BMI, and lower risk of both hypertension (OR: 0.52, p < 0.001) and diabetes (OR: 0.36, p < 0.001), but these findings were no longer apparent upon adjusting the regression models. No IFIH1/MDA5 gene variant was associated with any cardiometabolic risk factor. Conclusions: The influence of HLA-Cw6 on the cardiometabolic risk profile of psoriatic patients seems to be explained by other factors (age, sex, duration of the disease or arthritis) and not by this biomarker itself. Full article