An Overview of Advancements in the Bone Metastases in Endocrine Cancers: From Molecular Insights to Clinical Applications

Abstract

Bone metastases in endocrine cancers pose a major clinical challenge, significantly impacting patient morbidity and survival. This review highlights recent advancements in understanding the mechanisms of tumor-bone interactions, emphasizing the roles of osteoclast and osteoblast activity, immune modulation, and tumor dormancy. Novel diagnostic approaches, including advanced imaging modalities such as [68Ga]Ga-DOTA-FAPI-04 PET/CT and liquid biopsy techniques, have improved early detection and monitoring of metastatic progression. Additionally, therapeutic strategies have evolved with the development of bone-modifying agents (BMAs), targeted radionuclide therapies, and emerging immunotherapies, offering new avenues for treatment. Despite these advancements, skeletal-related events (SREs) remain a significant concern, underscoring the need for further research into optimizing treatment protocols and mitigating therapy resistance. Future research should focus on precision medicine approaches that integrate molecular profiling, artificial intelligence (AI) driven diagnostics, and personalized treatment strategies. Combination therapies, including bisphosphonates, denosumab, and novel Wnt or RANKL inhibitors, show promise in disrupting the metastatic cycle and improving patient outcomes. Additionally, the role of the tumor microenvironment in endocrine cancers with bone metastases requires further exploration to identify new therapeutic targets. Expanding clinical trials and fostering a multidisciplinary approach among oncologists, endocrinologists, and orthopedic specialists will be crucial in refining treatment strategies and enhancing the quality of life for affected patients.