Unraveling molecular signatures in rare bone tumors and navigating the cancer pathway landscapes for targeted therapeutics

Rare cancers (RCs), which account for over 20% of cancer cases, face significant research and treatment challenges due to their limited prevalence. This results in suboptimal outcomes compared to more common malignancies. Rare bone tumors (RBTs) constitute 5–10% of rare cancer cases and pose unique diagnostic complexities. The therapeutic potential of anti-cancer drugs for RBTs remains largely unexplored. Identifying molecular alterations in cancer-related genes and their associated pathways is essential for precision medicine in RBTs. Small molecule inhibitors and monoclonal antibodies targeting specific RBT-associated proteins show promise. Ongoing clinical trials aim to define RBT biomarkers, subtypes, and optimal treatment contexts, including combination therapies and immunotherapeutic agents. This review addresses the challenges in diagnosing, treating, and studying RBTs, shedding light on the current state of RBT biomarkers, potential therapeutic targets, and promising inhibitors. Rare cancers demand attention and innovative solutions to improve clinical outcomes.