Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma

Chondrosarcomas can be classified into various forms according to the presence or absence of a precursor lesion, location, and histological subtype. The new 2020 World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone classifies chondrogenic bone tumors as benign, intermediate (locally aggressive), or malignant, and separates atypical cartilaginous tumors (ACTs) and chondrosarcoma grade 1 (CS1) as intermediate and malignant tumors. respectively. Furthermore, the classification categorizes chondrosarcomas (including ACT) into eight subtypes: central conventional (grade 1 vs. 2–3), secondary peripheral (grade 1 vs. 2–3), periosteal, dedifferentiated, mesenchymal, and clear cell chondrosarcoma. Most chondrosarcomas are the low-grade, primary central conventional type. The rarer subtypes include clear cell, mesenchymal, and dedifferentiated chondrosarcomas. Comprehensive analysis of the characteristic imaging findings can help differentiate various forms of chondrosarcomas. However, distinguishing low-grade chondrosarcomas from enchondromas or high-grade chondrosarcomas is radiologically and histopathologically challenging, even for experienced radiologists and pathologists.

Section: Targets and Novel Treatment Optionsmentioning

confidence: 99%

Classification of Chondrosarcoma: From Characteristic to Challenging Imaging Findings

Kim

Lee

2023

“…If an IDH1 mutation is present, IDH1 inhibitors (e.g., ivosidenib) may be considered. Overall, the evidence for these substances is low [ 95 , 96 ].…”

Section: Chondrosarcomamentioning

confidence: 99%

Surgical Treatment of Bone Sarcoma

Bläsius

Delbrück

Hildebrand

et al. 2022

Bone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has improved for affected patients over the past decades, bone sarcomas are still critical conditions that require an interdisciplinary diagnostic and therapeutic approach. While radiotherapy plays a role especially in Ewing sarcoma and chemotherapy in Ewing sarcoma and osteosarcoma, surgery remains the main pillar of treatment in all three entities. After complete tumor resection, the created bone defects need to be reconstructed. Possible strategies are implantation of allografts or autografts including vascularized bone grafts (e.g., of the fibula). Around the knee joint, rotationplasty can be performed or, as an alternative, the implantation of (expandable) megaprostheses can be performed. Challenges still associated with the implantation of foreign materials are aseptic loosening and infection. Future improvements may come with advances in 3D printing of individualized resection blades/implants, thus also securing safe tumor resection margins while at the same time shortening the required surgical time. Faster osseointegration and lower infection rates may possibly be achieved through more elaborate implant surface structures.

“…Nonconventional treatments for chondrosarcoma include molecularly-targeted therapies, epigenetic approaches, immunotherapy, and herbal therapies [ 33 , 36 ]. Some of the targets for chondrosarcoma therapies involve mutations of isocitrate dehydrogenases IDH1 and IDH2 [ 37 , 38 , 39 , 40 ], angiogenesis [ 41 , 42 ], cyclin-dependent kinases (CDK) [ 43 ], tyrosine kinase inhibitor [ 44 ], mechanisms involved in the signaling pathway of Rapamycin (mTOR) [ 45 , 46 ], agents of hypomethylation, and histone deacetylase (HDAC) [ 47 , 48 , 49 ]. Clinical studies involving immune checkpoint inhibition are in the early stages and show promising results despite patients’ mixed responses to some inhibitors [ 50 , 51 , 52 ].…”

Section: Introductionmentioning

confidence: 99%

Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions

Gilbert

Tudor

Montanari

et al. 2023

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.