There is No Role (yet) for Axillary Sentinel Lymph Node Biopsy in Inflammatory Breast Cancer
Ashley D. Marumoto1*, Shirley Cheng2, Naoto T. Ueno1
1University of Hawai'i Cancer Center Inflammatory Breast Cancer Clinic and Research Program, Honolulu, HI, USA
2The University of Hawai’i John A. Burns School of Medicine, Honolulu, HI, USA,
Axillary staging has evolved from routine axillary dissection to sentinel node biopsy with selective omission of axillary staging for patients with early-stage, non-inflammatory breast cancer. For patients with inflammatory breast cancer, axillary dissection remains technically and oncologically necessary. However, studies have demonstrated a trend away from guideline concordant axillary surgery for patients with IBC without the literature to support it. Improved understanding of the biology and genetic drivers of the disease, systemic and locoregional therapies, and techniques may offer opportunities to de-escalate axillary surgery. This summarizes the history and role of axillary surgery in patients with IBC as of January 2026.
DOI: 10.29245/2690-0009/2026/1.1312 View / Download PdfFrom Genetics to Functional Neuronal Biology: Emerging Paths in Precision Psychiatry for Depression
Daphna Laifenfeld1*, Talia Cohen Solal1
NeuroKaire Ltd, Tel Aviv, Israel
Major depressive disorder (MDD) is a common and disabling condition with highly variable treatment response. Despite the availability of multiple antidepressant therapies, treatment selection remains largely empirical, resulting in prolonged trial-and-error care. Precision psychiatry seeks to improve outcomes by aligning treatment decisions with patient-specific biology. In this commentary, we expand on recent advances in precision approaches to depression, focusing on the role of genetics and its integration with functional brain biology. Pharmacogenetic (PGx) testing is the most established precision tool in clinical psychiatry and provides clear clinical value by informing antidepressant metabolism, exposure, and tolerability. By reducing avoidable adverse effects and guiding dose optimization, PGx represents an essential first step toward more individualized treatment. However, PGx alone does not directly address the neurobiological mechanisms that determine antidepressant efficacy. We discuss emerging complementary approaches, including neuroimaging, electrophysiologic biomarkers, and computational models, and highlight shared challenges in achieving robust, patient-level prediction. We then consider patient-derived neuronal assays as a functional extension of genetic information. These systems enable direct assessment of antidepressant effects on neuroplasticity, the capacity of neurons to modify structure and function, in human neurons, while preserving the patient’s inherited genetic background. We propose that integrating established genetic tools with functional neuronal readouts offers a promising path toward accelerating treatment selection and advancing precision psychiatry in depression.
DOI: 10.29245/2690-0009/2026/1.1313 View / Download PdfMutational Signatures in Pediatric Hepatoblastoma: Molecular Mechanisms and Prognostic Potential
Gustavo Dib Dangoni1, Talita Ferreira Marques Aguiar2*, Guilherme Henrique Souza Bomfim3, Ana Cristina Victorino Krepischi1*
1Department of Genetics and Evolutionary Biology, Institute of Biosciences, Human Genome and Stem-Cell Research Center, University of São Paulo, São Paulo, Brazil
2Department of Pathology, Texas Children's Hospital, Texas, USA
3Department of Molecular Pathobiology, New York University College of Dentistry. New York, USA
Cancer genomes reflect both the accumulation of somatic mutations and the underlying mutational processes that generate them. While somatic mutation burden provides a quantitative measure of genomic alterations, mutational signatures capture the mechanistic footprints of endogenous and exogenous DNA damage and repair pathways. This distinction is crucial in pediatric cancers, which typically exhibit low mutation burden arising from biologically distinct, developmentally constrained mechanisms. Recent large-scale genomic studies demonstrate that pediatric tumors harbor a restricted repertoire of COSMIC mutational signatures, in contrast to findings in adult cancers, which exhibit broader mutational diversity driven by cumulative environmental exposures. In this review, we systematically revisit, synthesize, and critically re-evaluate the current evidence on mutational signatures in pediatric malignancies, with a focus on hepatoblastomas.
DOI: 10.29245/2690-0009/2026/1.1309 View / Download PdfEpigenetics in DNA Repair Mechanism and their Relation to Cancer
Salavoura Aikaterini
Children's Hospital Agia Sophia, Athens, Greece
The epigenetic model for the development of cancer is based on the concept that cancer develops due to overall hypomethylation of the genome with concomitant hypermethylation of promoters of oncogenes. Recent research unravels the epigenetic mechanisms of the malignant transformation of the cell and it contributes to the development of more efficient therapies.
Methods. Detailed investigation of recent literature on PubMed using the keywords DNA repair, epigenetics
Conclusions. It is known that a prominent mechanism of the surveillance of the integrity of the genome is the DNA repair system that protects the cell from deleterious insults by the recruitment of the DNA Damage Response (DDR). Mutations of the genes of this complex system are associated with immunodeficiencies and a predisposition to cancer. Recently, defects of the epigenetic DNA repair sequential regulation are described in cancer tissues. The epigenetic dysfunction involves changes in the methylation patterns of promoters and genes, aberrant histone modifications and the expression of variants, deregulation of histone readers and miRNA processing which will be analyzed in the review.
DOI: 10.29245/2690-0009/2026/1.1310 View / Download PdfRecent Developments in Preimplantation Genetic Testing and Embryo Selection
DOI: 10.29245/2690-0009/2025/2.1306 View / Download PdfSantiago Munné, PhD¹²³*, Jonathan Anomaly, PhD²
¹Progenesis, La Jolla, CA, USA
²Herasight, Morrisville, NC, USA
³Overture Life, Coral Gables, FL, USA
Genetic and Epigenetic Aspects Linked to The Etiology of Autism
Claudia L. Arberas
Honorary consultant of Sección Genética médica Hospital de niños Dr. R. Gutiérrez, Gallo 1330 - Buenos Aires – Argentina
Autism is a childhood-onset neurodevelopmental disorder characterized by high heritability, a complex genetic basis, and a wide range of phenotypic expressions. Its etiology is identified in a significant proportion of cases and may involve chromosomal abnormalities, pathogenic variations in several genes, or environmental factors. However, in many cases, the underlying causes remain unexplained, even after comprehensive genetic testing in accordance with ACMG (American College of Medical Genetics and Genomics) guidelines.
The complex phenotype of autism includes a "core triad" of symptoms—impaired social interaction, restricted and repetitive behaviors—often accompanied by additional conditions such as language impairments, intellectual disability, epilepsy, hyperactivity, anxiety, and various other comorbidities.
In this paper, I aim to explore the interplay between genetic, epigenetic, and environmental factors to better understand the potential pathogenic mechanisms underlying this disorder, which continues to show a rising global prevalence.
DOI: 10.29245/2690-0009/2025/1.1302 View / Download PdfRegulatory T Cells in Cancer Immunotherapy: From Tumor Microenvironment Dynamics to Bispecific Antibody Approaches
Meenakshi Tanwar1 and Muthukumaran Venkatachalapathy2
1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA
2Department of Pathology, Yale University, New Haven, CT, USA
Regulatory T (Treg) cells are crucial in maintaining immune homeostasis and preventing autoimmunity1. However, within the tumor microenvironment (TME), Tregs shift their role towards immune suppression. In cancer, the immune system develops resistance, contributing to a suppressive TME. The TME plays a vital role in tumorigenesis2, and tumor-infiltrating lymphocytes (TILs) are key components of this environment. These lymphocytes consist of various cell types, including natural killer (NK) cells, CD8+ cytotoxic T cells, CD4+ helper T cells and regulatory T cells. Various interactions and immune responses occur between tumor cells and neighboring cells through the circulatory and lymphatic systems. These interactions include the upregulation of immune checkpoint molecules, the secretion of immunosuppressive cytokines, and alterations in the metabolic environment of effector T cells, among other mechanisms. This facilitates the tumor cells to evade immune detection, escape the immune system, and promote tumor growth and survival. In recent years, immunotherapy has emerged as one of the most promising treatments for cancer, significantly transforming the therapeutic landscape of cancer care. By harnessing the power of the immune system, immunotherapies target and combats tumor cells. Regulatory T cells have become key targets in the development of new immunotherapeutic strategies due to their pivotal role in immune evasion of cancer cells3. In this review, we delve into the molecular characteristics and immunosuppressive mechanisms of Tregs in cancer, with a focus on key molecules CD25 (IL-2 receptor α chain) and TIGIT (T cell immunoreceptor with Ig and ITIM domains), which play significant roles in tumor immune evasion. We also discuss the potential of bispecific antibodies (BsAbs) as a therapeutic treatment for tumor by selectively targeting Tregs markers (CD25 and TIGIT) within the tumor microenvironment.
DOI: 10.29245/2690-0009/2025/1.1301 View / Download Pdf