For localized chondrosarcomas, complete surgical removal is the most critical and often only curative treatment. The tumors are largely resistant to chemotherapy and radiation, making a successful, clean-margin surgery the primary determinant of a patient's long-term outcome.
A common diagnostic pitfall for rare sarcomas is the "oops surgery," where a surgeon removes a presumed benign mass that is later found to be malignant. This complicates definitive treatment, as the entire track of the initial surgery may also need to be removed to prevent recurrence.
Chondrosarcomas arise from chondrocytes, cells adapted to low-oxygen, low-nutrient joint environments. This cellular resilience makes them inherently resistant to traditional chemotherapies, which are most effective against cells with high metabolic and division rates.
Despite its name, the mesenchymal subtype of chondrosarcoma has a unique gene fusion that makes its biology distinct. Consequently, treatment follows protocols for Ewing sarcoma, including neoadjuvant chemotherapy, rather than the surgery-first approach used for conventional chondrosarcomas.
The IDH1 enzyme, part of the Krebs cycle, is mutated in up to 60% of chondrosarcomas, driving cancer growth. Drugs like Ivosidenib block this mutated enzyme, showing how basic metabolic pathways from textbooks are now at the forefront of targeted cancer therapy.
Researchers are exploring combination therapies for chondrosarcoma's heterogeneity. One strategy is to combine IDH1 inhibitors, which may work better on lower-grade tumors, with DR5 agonists, potentially more effective on higher-grade tumors, to attack different components of the cancer simultaneously.