Molecular Vulnerabilities in Fusion-Driven Neoplasms: Integrating Diagnostic Markers and Preclinical Drug Discovery

Structural alterations in the genome, particularly those leading to fusion oncogenes, represent cornerstone events in the biology of both solid and hematological malignancies. Over the past decade, these genetic rearrangements have evolved from serving as critical diagnostic and prognostic tools to becoming the linchpins for therapeutic intervention, especially within the framework of precision medicine. Advanced sequencing and molecular profiling technologies have vastly expanded our catalogue of clinically relevant fusion events, illuminating new targets for intervention. Yet, a pressing problem persists: resistance mutations frequently develop in response to targeted therapies, blunting their long-term efficacy and presenting a formidable barrier to durable patient benefit. Ongoing research continues to map fusion oncogene-driven pathways, but there remains a lack of streamlined translational workflows to turn these insights into timely and effective therapies.This Research Topic aims to accelerate the translation of molecular and structural discoveries into actionable clinical solutions for fusion-driven cancers. Central to this objective is the integration of computational methods, such as computer-aided drug design (CADD), virtual screening, and molecular dynamics, with robust experimental validation using advanced biological systems like 3D cell cultures and patient-derived organoids. A major focus is placed on drug repositioning, leveraging known compounds to target newly characterized fusion proteins or resistance variants. By fostering a multidisciplinary dialogue, the goal is to streamline the transition from detection and characterization to therapeutic innovation and functional validation, ultimately closing the current gap between genetic insight and clinical intervention.This Research Topic is focused on the translational workflow bridging the identification of fusion-driven biomarkers and the rational development of targeted therapies, while prioritizing studies that integrate computational and experimental approaches for robust preclinical evaluation. We welcome articles that address, but are not limited to, the following key themes:- Identification and characterization of genomic rearrangements and diagnostic biomarkers- Drug repositioning strategies for novel and resistance-associated fusion oncoproteins- Application of CADD, virtual screening, and molecular dynamics in drug discovery- Functional validation of drug candidates using in vitro 3D models and organoids- Mechanistic studies of resistance evolution and synergistic combinatorial therapiesWe invite Original Research, Reviews, Mini-Reviews, and Perspectives, with particular encouragement for studies that demonstrate the biological relevance of in silico findings through experimental validation. Studies relying solely on descriptive bioinformatics or clinical trials without functional insights will not be considered.Edwin Emilio Valdivia Malqui holds patent EP24176410.9 Topic editors: Luca Mologni, Mohammed BOUACHRINE Source: https://www.frontiersin.org/research-topics/79140/molecular-vulnerabilities-in-fusion-driven-neoplasms-integrating-diagnostic-markers-and-preclinical-drug-discovery