Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics.

Radiation Segmentectomy for Early Hepatocellular Carcinoma is Curative.

In this Expert Opinion, we provide the rationale for concluding that radiation segmentectomy (using RADSEG method), a technique of administrating ablative, complete necrosis-inducing trans-arterial Yttrium-90 (Y90) radiotherapy in limited-disease burden hepatocellular carcinoma (HCC), is curative. Currently, curative options for early stage and other carefully selected HCC patients include transplantation, resection, and ablation. Because of issues with organ availability, co-morbidities preventing resection, and tumor size and location limiting ablation, other treatments are necessary for this selected patient population.

Mcl-1 is a Gatekeeper Molecule to Regulate the Crosstalk Between Ferroptotic Agent-Induced ER Stress and TRAIL-Induced Apoptosis.

We previously reported that ferroptosis interplays with apoptosis through the integration of two independent pathways: the endoplasmic reticulum (ER) stress signaling pathway and the mitochondria-dependent apoptotic signaling pathway. In this study, we investigated a potential gatekeeper molecule, Mcl-1, between the two signal transduction pathways. Morphology studies and cell death analyses confirmed that a combination treatment of ferroptotic agent erastin (ERA) and apoptotic agent TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) synergistically enhances TRAIL-induced apoptosis in human pancreatic adenocarcinoma BxPC3 and human colorectal carcinoma HCT116 cells.

Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors.

Background: Peripheral nerve sheath tumors (PNSTs) encompass entities with different cellular differentiation and degrees of malignancy. Spatial heterogeneity complicates diagnosis and grading of PNSTs in some cases. In malignant PNST (MPNST) for example, single cell sequencing data has shown dissimilar differentiation states of tumor cells.

Genomic sequencing in diverse and underserved pediatric populations: parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

Purpose: Limited evidence evaluates parents' perceptions of their child's clinical genomic sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research (CSER) consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.

Methods: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure.

Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.

Desmosomes are adhesive cell contacts abundant in tissues exposed to mechanical strain, such as the stratified and simple epithelia of the epidermis and mucous membranes, as well as the myocardium. Besides their role in mechanical cell cohesion, desmosomes also modulate pathways important for tissue differentiation, wound healing and immune responses. Dysfunctional desmosomes, resulting from pathogenic variants in genes encoding desmosomal components, autoantibodies targeting desmosomal adhesion molecules or inflammation, cause the life-threatening diseases arrhythmogenic cardiomyopathy and pemphigus and contribute to the pathogenesis of inflammatory bowel diseases.

Neratinib Efficacy in Patients With EGFR Exon 18-Mutant Non-Small-Cell Lung Cancer: Findings From the SUMMIT Basket Trial.

Background: Activating mutations in the epidermal growth factor receptor (EGFR) gene occur in 7% to 23% of patients with non-small-cell lung cancer (NSCLC). A small proportion of these (3-5%) are exon 18 mutations. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), had activity in the phase II SUMMIT basket study.

Dermatofibrosarcoma Protuberans, Version 1.2025, NCCN Clinical Practice Guidelines In Oncology.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma and affects an estimated 1,500 people annually in the United States. DFSP frequently exhibits extensive local infiltration. Initial treatment is through surgical excision, and care should be taken to ensure that negative margins are achieved to minimize recurrence.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2025.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide criteria for selecting individuals for screening and offer recommendations for evaluating and managing lung nodules detected during initial and subsequent annual screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Weight and Blood-Based Markers of Cachexia Predict Disability, Hospitalization and Worse Survival in Cancer Immunotherapy Patients.

Background: Cancer-associated cachexia can inhibit immune checkpoint inhibitor (ICI) therapy efficacy. Cachexia's effect on ICI therapy has not been studied in large cohorts of cancer patients aside from lung cancer. We studied associations between real-world routinely collected clinical cachexia markers and disability-free, hospitalization-free and overall survival of cancer patients.

The Current Role of Circulating Tumor DNA in the Management of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer-related death by 2030. Early identification is rare, with a 5-year overall survival (OS) of less than 10%. Advances in the understanding of PDAC tumor biology are needed to improve these outcomes.

Trends in Immunotherapy (IO) Use and Survival Among Patients With High-Incidence Stage IV Cancers Across the United States.

Background And Objectives: IO has transformed cancer management, but its adoption in advanced cancer patients varies by tumor type. With more Stage IV patients undergoing surgery, understanding site-specific outcomes in these challenging patients is essential. We aimed to evaluate IO use and survival trends for Stage IV cancer patients across high-incidence cancers in the US.

Robust collection and processing for label-free single voxel proteomics.

With advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk tissues. However, such bulk measurement lacks spatial resolution and obscures tissue heterogeneity, precluding proteome mapping of tissue microenvironment. Here we report an integrated wet collection of single microscale tissue voxels and Surfactant-assisted One-Pot voxel processing method termed wcSOP for robust label-free single voxel proteomics.

Implementation of patient-reported outcome dashboards within the electronic health record to support shared decision-making in serious chronic illness.

Background: Attending to patient-reported outcomes (PROs) using data visualisation dashboards could enhance shared decision-making (SDM) and care delivery for serious chronic illnesses. However, few studies have evaluated real-world strategies and resulting implementation outcomes of PRO dashboards.

Method: From June 2020 to January 2022, we implemented an electronic health record (EHR)-integrated PRO dashboard for advanced cancer and chronic kidney disease.

Real-World Treatment Patterns and Clinical Outcomes in Patients With Multiple Myeloma Previously Treated With Lenalidomide and an Anti-CD38 Monoclonal Antibody.

Background: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment.

Materials And Methods: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed.

Variance in development of early and late cardiotoxicities in patients with lymphoma and myeloma receiving CAR T-cell therapies.

Cardiovascular adverse events (CVAEs) are recognized complications of chimeric antigen receptor (CAR) T-cell therapies. However, data are lacking regarding subtypes of adverse events that develop in patients with different malignancies, and little is known about the timeframe in which different cardiotoxicities are most likely to occur post-CAR T-cell therapies. In this study, 211 patients, including 138 lymphoma patients and 66 myeloma patients who received CAR T-cell therapies were retrospectively identified.

Targeting the CD74 signaling axis suppresses inflammation and rescues defective hematopoiesis in -familial platelet disorder.

Familial platelet disorder (FPD) is associated with germline mutations, establishing a preleukemic state and increasing the risk of developing leukemia. Currently, there are no intervention strategies to prevent leukemia progression. Single-cell RNA sequencing ( = 10) combined with functional analysis of samples from patients with -FPD ( > 75) revealed that FPD hematopoietic stem and progenitor cells (HSPCs) displayed increased myeloid differentiation and suppressed megakaryopoiesis because of increased activation of prosurvival and inflammatory pathways.

It Is Not Just About Storing Energy: The Multifaceted Role of Creatine Metabolism on Cancer Biology and Immunology.

Creatine, a naturally occurring compound in mammals, is crucial in energy metabolism, particularly within muscle and brain tissues. While creatine metabolism in cancer has been studied for several decades, emerging studies are beginning to clarify the sometimes-contradictory role creatine has in either the promotion or inhibition of cancer. On one hand, creatine can directly enhance anti-tumor CD8+ T-cell activity and induce tumor apoptosis, contributing to antitumor immunity.

Injury-induced Neuregulin-ErbB signaling from muscle mobilizes stem cells for whole-body regeneration in Acoels.

The activation of progenitor cells near wound sites is a common feature of regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body regeneration are still incompletely understood. The acoel undergoes whole-body regeneration using Piwi+ pluripotent adult stem cells (neoblasts) that accumulate at amputation sites early in the regeneration process. The EGFR signaling pathway has broad roles in controlling proliferation, migration, differentiation, and cell survival across metazoans.

Chromatin hubs drive key regulatory networks in leukemia.

In this issue of Molecular Cell, Gambi, Boccalatte, Hernaez, et al. apply multiomics followed by genetic engineering to define then characterize epigenetic hubs that regulate processes crucial for T-ALL and use this insight to offer new avenues for therapeutic targeting.

Bacillus subtilis-derived-exopolysaccharide halts depigmentation and autoimmunity in vitiligo.

Vitiligo has a complex multifactorial etiology involving a T-cell mediated autoimmune response to cutaneous melanocytes. Microbial dysbiosis has been assigned a contributing role in vitiligo etiology. Treating vitiligo can be a challenging task and finding novel treatment approaches is crucial.

Cigarette Smoking and Symptom Burden: Baseline Results From Nine ECOG-ACRIN Cancer Clinical Trials.

Context: Approximately 11% of cancer survivors smoke postdiagnosis.

Objectives: Understanding the relationship between smoking and perceived cancer-related symptoms may inform tobacco treatment interventions for this population.

Methods: From 2017 to 2021, 740 adults in 9 ECOG-ACRIN trials provided baseline data.