Molecular Mechanism, Pathogenesis, and Precision Therapeutics in Thyroid Cancer

Dear Colleagues,

Thyroid cancer incidence has risen steadily worldwide, presenting a significant clinical and public health challenge. While most cases have an excellent prognosis with standard treatment, a subset of patients with advanced, metastatic, or radioiodine-refractory disease face limited therapeutic options and poor outcomes. The last two decades have witnessed a paradigm shift in our understanding of thyroid cancer, driven by the comprehensive molecular characterization of its various subtypes. The discovery of key driver mutations (e.g., in BRAF, RAS, RET, TERT) and altered signaling pathways (MAPK, PI3K/AKT) has not only refined diagnostic and prognostic stratification but also paved the way for the development of molecularly targeted agents.

However, the rapid evolution of this field brings new complexities. Primary and acquired resistance to targeted therapies, the role of the tumor microenvironment and immune landscape, and the need for reliable biomarkers for early detection and monitoring remain critical unsolved issues. This Special Issue seeks to compile cutting-edge research that deepens our fundamental understanding of thyroid cancer biology and directly translates these discoveries into novel, precise therapeutic strategies to improve patient survival and quality of life.

This Special Issue aims to provide a comprehensive forum for disseminating high-quality research on the translational science of thyroid cancer. We welcome submissions that bridge the gap between foundational molecular discoveries and clinical application, focusing on elucidating pathogenic mechanisms and developing precision therapeutics.

This topic is firmly within the scope of the International Journal of Molecular Sciences, which emphasizes molecular biology, molecular pathology, and molecular aspects of disease mechanisms and therapeutics. The focus is deliberately tailored to be neither too broad nor too narrow, ensuring a cohesive collection of at least 10 articles that will offer a valuable snapshot of the field's current state and future directions. Upon successful completion, this collection may be considered for printing in book form.

In this Special Issue, original research articles and reviews (systematic, scoping, or comprehensive) are welcome. Research areas may include, but are not limited to, the following:

• Molecular Pathogenesis: Studies on novel genetic, epigenetic, and transcriptomic drivers of initiation, progression, and dedifferentiation.
• Tumor Microenvironment and Immunology: Investigations into stromal interactions, immune cell infiltration, and mechanisms of immune evasion in thyroid cancer.
• Preclinical Models and Drug Discovery: Development and use of novel cell lines, organoids, or animal models for testing targeted therapies and combination strategies.
• Resistance Mechanisms: Research elucidating how tumors evade current targeted therapies (e.g., kinase inhibitors) and strategies to overcome resistance.
• Precision Diagnostics and Biomarkers: Discovery and validation of molecular biomarkers for diagnosis, risk stratification, prognosis, and monitoring via tissue or liquid biopsy.
• Clinical Translational Studies: Clinical trials or correlative studies investigating the efficacy, safety, and molecular predictors of response to new therapeutic agents.

I look forward to receiving your outstanding contributions.

Prof. Dr. Laura Sterian Ward
Guest Editor

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