Does PARP Inhibition Sensitize Chondrosarcoma Cell Lines to Chemotherapy or Radiotherapy? Results From a Three-dimensional Spheroid Cell Model.

Background: Chondrosarcomas are well known for their resistance to conventional chemotherapy and radiotherapy treatment regimens, which is particularly detrimental in patients who have unresectable tumors. Recently, inhibition of poly(ADP-ribose) polymerase (PARP) by talazoparib was shown to sensitize chondrosarcoma cell lines to chemotherapy (temozolomide) or radiotherapy, irrespective of isocitrate dehydrogenase (IDH) mutation status. Because two-dimensionally grown cell lines have limitations and may not accurately represent the clinical response to drug treatment, we aimed to use a more representative three-dimensional alginate spheroid chondrosarcoma model.

A murine mesenchymal stem cell model for initiating events in osteosarcomagenesis points to CDK4/CDK6 inhibition as a therapeutic target.

Osteosarcoma is a high-grade bone-forming neoplasm, with a complex genome. Tumours frequently show chromothripsis, many deletions, translocations and copy number alterations. Alterations in the p53 or Rb pathway are the most common genetic alterations identified in osteosarcoma.

Targeting the NAD Salvage Synthesis Pathway as a Novel Therapeutic Strategy for Osteosarcomas with Low NAPRT Expression.

For osteosarcoma (OS), the most common primary malignant bone tumor, overall survival has hardly improved over the last four decades. Especially for metastatic OS, novel therapeutic targets are urgently needed. A hallmark of cancer is aberrant metabolism, which justifies targeting metabolic pathways as a promising therapeutic strategy.

Selection of Effective Therapies Using Three-Dimensional Modeling of Chondrosarcoma.

Chondrosarcomas are a group of cartilaginous malignant neoplasms characterized by the deposition of chondrogenic extracellular matrix. Surgical resection is currently the only curative treatment option, due to their high resistance to conventional chemotherapy and radiotherapy. Novel therapeutic treatment options may improve outcome.

Beyond the Influence of Mutations: Exploring Epigenetic Vulnerabilities in Chondrosarcoma.

Mutations in the isocitrate dehydrogenase ( or ) genes are common in enchondromas and chondrosarcomas, and lead to elevated levels of the oncometabolite D-2-hydroxyglutarate causing widespread changes in the epigenetic landscape of these tumors. With the use of a DNA methylation array, we explored whether the methylome is altered upon progression from mutant enchondroma towards high-grade chondrosarcoma. High-grade tumors show an overall increase in the number of highly methylated genes, indicating that remodeling of the methylome is associated with tumor progression.

Mass spectrometry imaging of endogenous metabolites in response to doxorubicin in a novel 3D osteosarcoma cell culture model.

Three-dimensional (3D) cell culture is a rapidly emerging field, which mimics some of the physiological conditions of human tissues. In cancer biology, it is considered a useful tool in predicting in vivo chemotherapy responses, compared with conventional two-dimensional (2D) cell culture. We have developed a novel 3D cell culture model of osteosarcoma composed of aggregated proliferative tumour spheroids, which shows regions of tumour heterogeneity formed by aggregated spheroids of polyclonal tumour cells.

Radiotherapy resistance in chondrosarcoma cells; a possible correlation with alterations in cell cycle related genes.

Background: Conventional chondrosarcomas are malignant cartilage tumors considered radioresistant. Nevertheless, retrospective series show a small but significant survival benefit for patients with locally advanced disease treated with radiotherapy. And, in daily practice when considered inoperable their irradiation is an accepted indication for proton beam radiotherapy.

The Future in Disease Models for Mass Spectrometry Imaging, Ethical Issues, and the Way Forward.

Mass Spectrometry Imaging (MSI) has evolved into a valuable tool for research into and the diagnosis of disease pathology. The ability to perform multiplex analysis of a wide range of molecules (e.g.