Search Results (1,620)

Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in and functionally linked to the pathogenesis of IBD. Beyond the gastrointestinal manifestations, IBD patients frequently suffer from psychiatric comorbidities, particularly depression and anxiety. It remains unclear whether these disorders arise solely from reduced quality of life or whether they share overlapping biological mechanisms with IBD. This review aims to explore the bidirectional relationship between IBD and depressive disorders (DDs), with a focus on four key shared mechanisms: immune dysregulation, genetic susceptibility, alterations in gut microbiota composition, and dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. By examining recent literature, we highlight how these interconnected systems may contribute to both intestinal inflammation and mood disturbances. Furthermore, we discuss the reciprocal pharmacologic interactions between IBD and DDs: treatments for IBD, such as TNF-alpha and integrin inhibitors, have demonstrated effects on mood and anxiety symptoms, while certain antidepressants appear to exert independent anti-inflammatory properties, potentially reducing the risk or severity of IBD. Overall, this review underscores the need for a multidisciplinary approach to the care of IBD patients, integrating psychological and gastroenterological assessment. A better understanding of the shared pathophysiology may help refine therapeutic strategies and support the development of personalized, gut–brain-targeted interventions. Full article

Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article

Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy defined by the uncontrolled proliferation of lymphoid precursors. Accurate diagnosis and effective therapeutic strategies hinge on a comprehensive understanding of the genetic and molecular landscape of ALL. This review synthesizes the latest updates in cytogenetic and molecular classifications, emphasizing the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) revisions. Key chromosomal alterations such as BCR::ABL1 and ETV6::RUNX1 and emerging subtypes including Ph-like ALL, DUX4, and MEF2D rearrangements are examined for their prognostic significance. Furthermore, we assess novel diagnostic tools, notably next-generation sequencing (NGS) and optical genome mapping (OGM). While NGS excels at identifying point mutations and small indels, OGM offers high-resolution structural variant detection with 100% sensitivity in multiple validation studies. These advancements enhance our grasp of leukemogenesis and pave the way for precision medicine in both B- and T-cell ALL. Ultimately, integrating these innovations into routine diagnostics is crucial for personalized patient management and improving clinical outcomes. Full article

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial–mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Background: The progression of Alzheimer’s Disease (AD) deeply affects not only the diagnosed person but also their close relatives, who are often called to take on the role of informal caregivers. This transition is frequently unplanned and emotionally complex, yet poorly understood in its deeper processual dimensions. This study aims to explore and theorize the transition experienced by a family member becoming the primary informal caregiver for a person with advanced AD. Methods: A qualitative study based on the Constructivist Grounded Theory according to Charmaz’s approach (2006) was conducted. In-depth interviews were carried out with 10 participants who had become informal caregivers for a loved one with advanced AD. Data were analyzed using initial coding, focused coding, the constant comparative method, and theoretical coding. Results: Ten caregivers (mean age 39 years, range 35–54; nine females) of patients with advanced AD participated in the study. The analysis revealed a complex, emotionally intense caregiving experience marked by sacrifice, feelings of powerlessness, identity loss, and the necessity of sharing caregiving responsibilities. A core category emerged: A Silent and Certain Willingness to Care, representing the caregivers’ deep, often unconscious commitment to prioritize the care of their loved ones above their own needs. Four interconnected phases characterized the caregiving process: (1) The Changing Daily Life—involving significant sacrifices in personal and social life; (2) Feeling Powerless—confronting the inevitable decline without means to alter the course; (3) Losing Oneself—experiencing physical and psychological exhaustion and a sense of identity loss; and (4) Sharing with Others—seeking external support to sustain caregiving. These findings highlight the evolving nature of becoming a caregiver and the enduring dedication that sustains this role despite the challenges. Conclusions: The progression of AD deeply transforms the lives of caregivers, who become co-sufferers and active participants in the disease’s management. The results underscore the urgency of designing integrative care strategies—including psychological, social, and potentially technological support—that can enhance both patient outcomes and caregiver resilience. Grounded in real-world experiences, this study contributes to the broader neurodegeneration discourse by emphasizing caregiving as a critical factor in long-term disease management and therapeutic success. Full article

Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article

Clozapine, a second-generation antipsychotic known for its effectiveness in treating resistant schizophrenia, is often linked with serious hematological side effects, particularly neutropenia and agranulocytosis. This review investigates the underlying pathophysiological mechanisms of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA), outlines associated risk factors, and evaluates current clinical management strategies. Clozapine’s pharmacological profile, marked by its antagonism of dopamine D4 and serotonin receptors, contributes to both its therapeutic advantages and hematological toxicity. Epidemiological data show a prevalence of CIN and CIA at approximately 3.8% and 0.9%, respectively, with onset typically occurring within the first six months of treatment. Key risk factors include older age, Asian and African American ethnicity, female sex, and certain genetic predispositions. The development of CIN and CIA may involve bone marrow suppression and autoimmune mechanisms, although the exact processes remain partially understood. Clinical presentation often includes nonspecific symptoms such as fever and signs of infection, necessitating regular hematological monitoring in accordance with established guidelines. Management strategies include dosage adjustments, cessation of clozapine, and the administration of granulocyte colony-stimulating factors (G-CSF). Advances in pharmacogenomics show promise for predicting susceptibility to CIN and CIA, potentially improving patient safety. This review emphasizes the importance of vigilant monitoring and personalized treatment approaches to reduce the risks associated with clozapine therapy. Full article

Background: The dual nature of cannabis, as both a promising therapeutic tool and a widely used recreational substance with potential risks, raises important societal controversies, including its unclear impacts regarding mental health. This narrative review provides a comprehensive overview of cannabis, addressing (i) its historical context; (ii) its chemical composition and pharmacokinetics; (iii) its pharmacological effects; (iv) its negative impacts on physiological and mental health; (v) its potential use as a drug for the treatment of neurological and psychiatric disorders; (vi) its relationship with the gut microbiome and how this interaction might influence mental functioning; (vii) the pathophysiology, prevalence, comorbidities, and treatment strategies of cannabis use disorder; and (viii) social perspectives on its legalization. Results: Cannabis presents a complex chemical profile and pharmacokinetics that show promise in treating numerous neurological, psychiatric, and psychological conditions. However, its use carries risks, which depend on factors such as compound concentration, dosage, consumption method, frequency of use, and individual vulnerability. Cannabis use disorder seems to be less severe than other substance use disorders, but it still constitutes a significant concern, as its manifestation is not uniform across all users. Conclusions: Cannabis demands a thorough understanding that goes beyond simplistic explanations and prejudices, standing as a plant of substantial clinical significance and highlighting the importance of personalized approaches to its use and increased awareness of how individuals respond to its effects. Full article

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article