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 Pdf