Chondrosarcoma Resistance to Radiation Therapy: Origins and,Potential Therapeutic Solutions

Antoine Gilbert 1, Mihaela Tudor 2,3, Juliette Montanari 1, Kevin Commenchail 1 , Diana Iulia Savu 2 ,Paul Lesueur 4,5,6 and François Chevalier 1,*

Simple Summary: This review article aims in describing the origins of chondrosarcoma radiation-resistance and proposes several potential solutions in order to improve the treatment, in regard with
tumor grade and characteristics.

Abstract: Chondrosarcoma is a malignant cartilaginous tumor that is particularly chemoresistant and radioresistant to X-rays. The first line of treatment is surgery, though this is almost impossible
in some specific locations. Such resistances can be explained by the particular composition of the tumor, which develops within a dense cartilaginous matrix, producing a resistant area where the
oxygen tension is very low. This microenvironment forces the cells to adapt and dedifferentiate into cancer stem cells, which are described to be more resistant to conventional treatments. One of the
main avenues considered to treat this type of tumor is hadrontherapy, in particular for its ballistic properties but also its greater biological effectiveness against tumor cells. In this review, we describe
the different forms of chondrosarcoma resistance and how hadrontherapy, combined with other treatments involving targeted inhibitors, could help to better treat high-grade chondrosarcoma