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Advances in the Translational Preclinical Research
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Advances in the Translational Preclinical Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 May 2026 | Viewed by 5728

Special Issue Editor

Dr. Mariano Gabri

E-Mail Website
Guest Editor
Centro de Oncología Molecular y Traslacional, Universidad Nacional de Quilmes, Bernal B1876BXD, Argentina
Interests: cancer; active immunotherapy; TACA; aberrant glycosylation; mimicry

Special Issue Information

Dear Colleagues,

Despite significant advances in cancer research, substantial challenges persist in the fight against this disease. Translational preclinical research plays a crucial role in this process by generating essential data to enhance drug efficacy, minimize toxicity, and establish effective management protocols. In the early stages of developing a novel therapy, the drug discovery process focuses on identifying and developing compounds that specifically target validated cancer pathways. Once a lead compound is selected, it undergoes an optimization process to improve its potency, selectivity, and safety profile. Throughout this process, in silico, in vitro, and in vivo experiments are conducted to deepen the understanding of the biological mechanisms underlying the evaluated cancer treatment. This Special Issue seeks to showcase original preclinical research focused on the evaluation of innovative drugs and treatments, also highlighting ongoing efforts to translate scientific discoveries into effective cancer therapies with the potential to benefit patients.

Dr. Mariano Gabri
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • translational preclinical research
  • drug discovery
  • cancer therapies
  • in vitro and in vivo experiments
  • biological mechanisms

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Published Papers (4 papers)

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Research

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17 pages, 1525 KB  
Article
Novel Mixed Cancer-Cell Models Designed to Capture Inter-Patient Tumor Heterogeneity for Accurate Evaluation of Drug Combinations
by Sampreeti Jena, Daniel C. Kim, Adam M. Lee, Weijie Zhang, Kevin Zhan, Radwa M. Elmorsi, Yingming Li, Scott M. Dehm and R. Stephanie Huang
Int. J. Mol. Sci. 2026, 27(1), 413; https://doi.org/10.3390/ijms27010413 - 30 Dec 2025
Cited by 2 | Viewed by 738
Abstract
Disease heterogeneity across a diverse patient cohort poses challenges to cancer drug development due to inter-patient variability in treatment responses. However, current preclinical models fail to depict inter-patient tumor heterogeneity, leading to a high failure rate when translating preclinical leads into clinical successes. [...] Read more.
Disease heterogeneity across a diverse patient cohort poses challenges to cancer drug development due to inter-patient variability in treatment responses. However, current preclinical models fail to depict inter-patient tumor heterogeneity, leading to a high failure rate when translating preclinical leads into clinical successes. We integrated the expression profiles of prostate cancer (PC) lines and castration-resistant PC (CRPC) patient tumors to identify cell-lines that transcriptomically match distinct tumor subtypes in a clinical cohort. Representative cell-lines were co-cultured to create “mixed-cell” models depicting inter-patient heterogeneity in CRPC, which were employed to assess drug combinations. When drug combinations previously tested in CRPC clinical cohorts were assessed to establish proof of concept, in vitro responses measured in our models concurred with their known clinical efficacy. Additionally, novel drug combinations computationally predicted to be efficacious in heterogeneous tumors were evaluated. They demonstrated preclinical efficacy in the mixed-cell models, suggesting they will likely benefit heterogeneous patient cohorts. Furthermore, we showed that the current practice of screening cell-lines/xenografts separately and aggregating their responses, failed to detect their efficacy. We believe that the application of our models will enhance the accuracy of preclinical drug assessment, thereby improving the success rate of subsequent clinical trials. Full article
(This article belongs to the Special Issue Advances in the Translational Preclinical Research)
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42 pages, 5506 KB  
Article
From Genetic Engineering to Preclinical Safety: A Study on Recombinant Human Interferons
by Thelvia I. Ramos, Carlos A. Villacis-Aguirre, Emilio Lamazares, Viana Manrique-Suárez, Felipe Sandoval, Cristy N. Culqui-Tapia, Sarah Martin-Solano, Rodrigo Mansilla, Ignacio Cabezas, Oliberto Sánchez, Sergio Donoso-Erch, Natalie C. Parra, María A. Contreras and Nelson Santiago-Vispo
Int. J. Mol. Sci. 2025, 26(24), 11982; https://doi.org/10.3390/ijms262411982 - 12 Dec 2025
Viewed by 1508
Abstract
There is a critical gap in the preclinical research of recombinant human interferons (rhIFNα-2b and rhIFN-γ), as most studies focus on modified variants, which complicates the understanding of the native molecules’ properties. This study addresses this limitation by comprehensively evaluating the structural stability [...] Read more.
There is a critical gap in the preclinical research of recombinant human interferons (rhIFNα-2b and rhIFN-γ), as most studies focus on modified variants, which complicates the understanding of the native molecules’ properties. This study addresses this limitation by comprehensively evaluating the structural stability and intrinsic toxicity of purified IFNs. Our findings confirm that both interferons retain their bioactivity (antiviral, antiproliferative, and immunomodulatory) and exhibit remarkable stability under controlled conditions. Accelerated stability assays showed that neither protein lost biological potency after 18 days at various temperatures, supporting their potential as liquid formulations. Acute and sub-chronic toxicity studies in rodent, non-rodent, and higher-organism animal models showed no signs of toxicity, even at doses 100 to 300 times higher than therapeutic levels. These assays, combined with the absence of pyrogens, support a favorable safety profile for clinical use, with no evidence of systemic or structural damage. This work establishes a reproducible experimental model and lays the groundwork for future preclinical evaluations. We underscore the importance of characterizing the safety profile of active pharmaceutical ingredients from the earliest stages of biopharmaceutical development to ensure a safe and well-founded transition to human clinical trials. Furthermore, these results open the door for the development of advanced formulations and alternative routes of administration, such as the intranasal route, an area with significant potential. Full article
(This article belongs to the Special Issue Advances in the Translational Preclinical Research)
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Review

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19 pages, 1083 KB  
Review
Circulating RNA as a Functional Component of Liquid Biopsy in Cancer: Concepts, Classification, and Clinical Applications
by Kyung-Hee Kim and Byong Chul Yoo
Int. J. Mol. Sci. 2026, 27(5), 2403; https://doi.org/10.3390/ijms27052403 - 5 Mar 2026
Viewed by 615
Abstract
Liquid biopsy has become an integral component of precision oncology, with circulating tumor DNA serving as the dominant analyte for genomic profiling and disease monitoring. However, DNA-based approaches are intrinsically limited in their ability to capture dynamic cellular states, functional adaptation, and tumor–host [...] Read more.
Liquid biopsy has become an integral component of precision oncology, with circulating tumor DNA serving as the dominant analyte for genomic profiling and disease monitoring. However, DNA-based approaches are intrinsically limited in their ability to capture dynamic cellular states, functional adaptation, and tumor–host interactions. Circulating RNA has emerged as a complementary class of liquid biopsy biomarkers that reflects active transcriptional programs and systemic biological responses. In this review, we conceptualize circulating RNA as a liquid transcriptome and propose a structured classification framework based on physical carriers, RNA biotypes, and layers of biological interpretation. We describe how circulating RNA signals encode tissue-of-origin information, cell-state dynamics, and host immune responses, thereby enabling system-level insight into cancer biology beyond mutation-centric analyses. Recent large-scale profiling efforts and advances in extracellular RNA characterization further support the biological relevance and analytical feasibility of circulating RNA across diverse biofluids. We discuss emerging applications of circulating RNA across the cancer continuum, including early cancer detection and multi-cancer screening, tissue-of-origin inference, longitudinal monitoring of treatment response, detection of adaptive resistance, and immunotherapy stratification. In parallel, we critically examine key technical, analytical, and computational challenges that currently limit reproducibility and clinical translation, emphasizing the importance of standardized workflows, transparent reporting, and multi-center validation. Finally, we outline future directions for integrating circulating RNA with genomic and proteomic biomarkers, supported by advances in artificial intelligence and machine learning. Collectively, this review positions circulating RNA as a functionally informative and clinically promising component of next-generation liquid biopsy strategies in oncology. Full article
(This article belongs to the Special Issue Advances in the Translational Preclinical Research)
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21 pages, 1675 KB  
Review
Modeling Glioblastoma with Brain Organoids: New Frontiers in Oncology and Space Research
by Laura Begani, Luigi Gianmaria Remore, Stefania Ragosta, Massimiliano Domenico Rizzaro, Laura Guarnaccia, Giovanni Andrea Alotta, Laura Riboni, Monica Rosa Miozzo, Emanuela Barilla, Chiara Gaudino, Marco Locatelli, Emanuele Garzia, Giovanni Marfia and Stefania Elena Navone
Int. J. Mol. Sci. 2025, 26(21), 10664; https://doi.org/10.3390/ijms262110664 - 1 Nov 2025
Cited by 1 | Viewed by 2444
Abstract
Glioblastoma (GBM) is the most malignant primary brain tumor, characterized by extensive heterogeneity, invasiveness, infiltrating behavior, and resistance to standard therapies, including radiation and temozolomide (TMZ). Despite considerable efforts in investigating its pathophysiology, GBM represents one of the most challenging cancers to treat, [...] Read more.
Glioblastoma (GBM) is the most malignant primary brain tumor, characterized by extensive heterogeneity, invasiveness, infiltrating behavior, and resistance to standard therapies, including radiation and temozolomide (TMZ). Despite considerable efforts in investigating its pathophysiology, GBM represents one of the most challenging cancers to treat, with a median survival rate under 15 months and a 5-year survival rate below 5%. A major barrier to progress in GBM therapy development is the lack of reliable preclinical models that faithfully recapitulate the tumor’s molecular heterogeneity, invasive behavior, and complex microenvironment. Traditional cell lines and xenograft models often fail to reflect the key pathological features of human GBM, including immune suppression, vascular abnormalities, and treatment resistance. In recent years, attention has focused on the development of numerous clinically relevant GBM models based on brain organoids as a powerful “disease-in-a-dish” model. They strongly mimic GBM key histopathological and molecular features, such as the tumor’s cellular heterogeneity, genetic landscape, and microenvironment, enabling more accurate studies of tumor biology, invasion, and therapeutic response in a controlled in vitro setting. Notably, research in microgravity offers a unique and promising platform to study cancer biology under conditions that enhance tissue self-organization, mimic aspects of tumor growth, and potentially unveil novel therapeutic vulnerabilities. This review compares organoids to conventional preclinical models, tracing their historical development and salient features, focusing on the preparation and use of organoids in GBM research. We also introduce a novel and promising field of organoid application: space-based organoid brain research. Full article
(This article belongs to the Special Issue Advances in the Translational Preclinical Research)
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