Viral pathogens in bone- and bone-marrow derived malignancies: Friends or foes?

BONE: and bone-marrow associated cancers, including osteosarcoma, Ewing sarcoma, multiple myeloma, and various leukemias, are highly aggressive tumors with limited therapeutic options and poor outcomes. Viruses play a paradoxical role in these diseases, acting both as pathogenic drivers and as potential therapeutic agents. On one hand, oncogenic viruses such as Epstein-Barr virus (EBV), human T-cell leukemia virus type 1 (HTLV-1), and hepatitis viruses have been implicated in the initiation and progression of certain hematologic and skeletal malignancies. On the other hand, oncolytic viruses have emerged as promising 'friends,' engineered to selectively infect, lyse, and stimulate immune responses against malignant cells within the unique microenvironment of bone and bone marrow. This duality raises critical questions about how viral biology intersects with cancer pathogenesis and therapy. In this review, we explore the evidence for viral pathogens as both foes that contribute to tumorigenesis and friends that can be harnessed as novel therapeutic platforms. We further highlight delivery challenges, safety considerations, and translational opportunities that may shape the future of virotherapy for bone and marrow cancers.