Editerial

Translational Disease Mechanisms: From Vascular Injury to Metabolic and Tumor Microenvironments

Sang Hyun Ahn¹ 

Vascular dysfunction, metabolic dysregulation, and remodeling of the tumor microenvironment are not independent pathophysiological processes. Rather, they constitute a single, integrated axis that operates across a wide spectrum of major diseases. Networks governing inflammation, endothelial injury, fibrosis, angiogenesis, and cellular stress responses underlie disease initiation and progression, spanning cardiovascular emergencies such as acute coronary syndrome, metabolic disorders represented by MAFLD, hepatic steatosis, and fibrosis, as well as tumor growth and metastasis driven by cancer-associated fibroblast (CAF)–mediated stromal dynamics. This integrative perspective marks a paradigm shift from traditional organ- or disease-centered approaches toward an interventional and systems-based medical framework that conceptualizes vascular, metabolic, stromal, and immune interactions as a continuous pathophysiological spectrum.

Special Issue 2 highlights this transition by showcasing how basic biology, preclinical research, clinical intervention, and emerging precision technologies converge around a shared disease mechanism axis.

The case report entitled “Successful Primary PCI in a 78-Year-Old Female Patient With Two STEMIs Due to Total Occlusion of the Distal RCA” exemplifies the clinical modulation of acute coronary syndrome pathophysiology through timely vascular intervention. In this report, rapid diagnosis of distal RCA total occlusion in an elderly female patient with inferior STEMI was followed by thrombus aspiration, drug-eluting stent implantation, and IVUS-guided post-dilatation, successfully restoring TIMI 3 flow without complications. This case underscores the critical value of time-sensitive vascular rescue in minimizing ischemia–reperfusion injury. Importantly, it provides clinical evidence that advanced age alone should not preclude PCI, reinforcing image-guided intervention as a cornerstone strategy for myocardial preservation and long-term prognosis—fully aligned with the Special Issue’s focus on vascular pathophysiology-driven precision intervention.

The article “CAF Markers in Cancers: Periostin and Stromal Signatures in Colon Cancers” elucidates the heterogeneity of cancer-associated fibroblasts and identifies periostin-driven stromal signaling as a central molecular axis promoting epithelial–mesenchymal transition, angiogenesis, and metastasis in colorectal cancer. By integrating a spectrum of CAF markers—including POSTN, FAP, PDGFRβ, PDPN, S100A4, and LTBP2—from a multi-omics perspective, the study establishes a robust pathophysiological framework for stromal–vascular–tumor interactions. Furthermore, it proposes the clinical translational potential of stromal-targeted strategies such as periostin-directed radiopharmaceuticals and blocking antibodies. These findings support the use of CAF patterns as signaling-based biomarkers and therapeutic targets, enabling patient stratification according to stromal subtypes and positioning stromal vascular remodeling as a critical focus of precision oncology. This work represents a key contribution driving the Special Issue’s paradigm of stroma-based precision cancer therapy.

The study “From Bench to Therapy: Human Fatty Liver Organoid Models for Disease Mechanism Discovery and Precision Drug Development” addresses the limitations of systemic anti-angiogenic therapies, particularly the activation of compensatory angiogenic pathways following VEGF inhibition. To overcome these challenges, the authors highlight local vascular-targeted delivery strategies—such as TAE, TACE, HAIC, and EUS-FNI—as emerging therapeutic paradigms. These approaches enable high intratumoral drug accumulation, minimize systemic toxicity, and induce central ischemia and cellular necrosis through image-guided localized administration. The potential scalability of automated, high-efficiency delivery platforms and their synergistic application with immunotherapies position these strategies as next-generation precision treatments aimed at mechanistically suppressing tumor angiogenesis, in strong alignment with the objectives of this Special Issue.

 Similarly, “Emerging Vascular-Targeted Strategies for Gastric Cancer: A Novel Local Delivery Approach” emphasizes tumor angiogenesis as a major driver of poor prognosis and therapeutic resistance in gastric cancer. The study presents compelling clinical evidence that localized vascular-targeted drug delivery can overcome the resistance and toxicity limitations of systemic anti-angiogenic therapy. By maximizing intratumoral drug concentration while minimizing systemic exposure, these image-guided approaches effectively block compensatory neovascularization commonly observed with VEGF-based therapies. Notably, their applicability to elderly and chemotherapy-intolerant patients, as well as their potential integration with immunotherapy, supports the development of patient-tailored precision oncology platforms. This work redefines interventional vascular-targeted therapy as a core axis of next-generation precision medicine.  

Collectively, the studies in this Special Issue address distinct diseases yet converge on a shared pathophysiological continuum characterized by vascular-driven metabolic disruption, stromal and immune reprogramming, and altered therapeutic responsiveness. In vascular medicine and oncology alike, localized vascular-targeted drug delivery strategies transcend the limitations of systemic anti-angiogenic agents, offering refined interventional precision that suppresses therapeutic resistance while minimizing toxicity.

Looking forward, these insights are expected to catalyze the development of combined vascular-targeted local delivery with immunomodulatory and anti-fibrotic therapies, CAF and periostin-based patient stratification strategies, and organoid-CRISPR-AI platforms for predictive drug response modeling. Such advances will accelerate precision stromal-targeted therapeutics and facilitate cross-disease drug discovery by targeting shared vascular-metabolic-stromal pathways across cardiovascular, metabolic, and oncologic conditions. 

Future medicine must move beyond rigid organ- or disease-specific boundaries and embrace a systems-level framework centered on the dynamic interplay among vascular, metabolic, stromal, and immune networks. The contributions in this Special Issue collectively support this transformation, offering a translational roadmap that integrates interventional, molecular, and precision medicine strategies grounded in the continuity of in vivo pathophysiology.

HRP will continue to strengthen its role as a translational medicine platform journal, fostering cross-disciplinary collaboration and enabling the conversion of mechanistic insights into clinical value. We hope this Special Issue stimulates interdisciplinary dialogue and contributes to the expansion of an integrated research ecosystem spanning vascular, metabolic, and tumor biology.

Together for Global Health.

Editorial Board of Healthcare Research and Practice

Global Health Research Network (GHRN)