Anaplastic thyroid cancer (ATC), a rare yet highly aggressive malignancy, continues to represent a major clinical challenge.

A recent review published in Genes & Diseases offers a comprehensive overview of the molecular mechanisms, diagnostic approaches, and therapeutic strategies driving current and future management of this lethal disease.

ATC, accounting for a small percentage of thyroid cancers, progresses rapidly and resists conventional therapies, underscoring the urgency for innovative treatment paradigms.

At the core of ATC’s pathogenesis are genetic aberrations, with prominent alterations in MAPK and PI3K-AKT-mTOR signalling pathways.

These dysregulated pathways promote unchecked cellular proliferation, survival, and metastasis.

Mutations in genes such as BRAF, RAS, PIK3CA, TP53, and TERT have emerged as key drivers of ATC development and progression.

Understanding the interplay between these mutations has enabled refined subclassifications of ATC, potentially informing personalised therapeutic approaches.

The review emphasises the significance of targeted therapies, especially BRAF and MEK inhibitors, in improving patient outcomes.

In particular, dual inhibition strategies have demonstrated efficacy in shrinking tumours and enabling surgical interventions.

While trimodal therapy—a combination of surgery, chemotherapy, and radiation—remains the cornerstone for localised disease, its limitations in advanced ATC highlight the need for additional therapeutic avenues.

Immunotherapy has gained traction as a complementary modality.

The tumour microenvironment of ATC, marked by immune cell infiltration and PD-L1 overexpression, presents opportunities for immune checkpoint inhibitors.

However, response rates remain variable, and research is ongoing to optimise patient selection and treatment combinations.

Diagnostic innovations are also covered in detail, including the comparative efficacy of fine needle aspiration (FNA) versus core needle biopsy (CNB) and the utility of 18F-FDG PET/CT imaging in staging and treatment planning.

Advances in immunohistochemical markers and liquid biopsies hold promise for earlier detection and real-time monitoring of therapeutic response.

The article concludes by highlighting the emerging role of mitochondrial metabolism as a therapeutic target and the potential of novel agents, including nanoparticles and oncolytic viruses, to enhance radioiodine uptake and overcome therapeutic resistance.

Source: Compuscript Ltd