In this publication we report how oncofetal CS is regulated in osteosarcoma, the most serious bone cancer worldwide affecting mainly children and young adults. Osteosarcoma cells grow under chronic stress inflicted by the tumor microenvironment. To survive chronic stress, osteosarcoma must find ways to adapt to harsh conditions.

In this publication, we report that oncofetal CS is regulated by, and required for, the cellular stress response to unfolded proteins. When osteosarcoma cells encounter proteotoxic stress, they respond by increasing oncofetal CS content that in turn supports survival under acute and chronic cell stress. We find that oncofetal CS is required for survival of osteosarcoma during stress conditions. Targeting oncofetal CS presentation on proteoglycans impairs the cellular stress response leading to cell death. We also find that oncofetal CS-dependent stress management supports metastatic tumor growth by protecting osteosarcoma cells from cell death induced by loss of cellular attachment (Anoikis).

Oncofetal CS constitutes a potential ‘Achilles heel’ in osteosarcoma that could be targeted by Vartumab-based therapies.

Read more about it here: https://doi.org/10.1038/s41419-026-09151-9