Sarcoma Models and Therapeutics Lab

Research

Our group focuses on three main areas of osteosarcoma research, with the overall aim of increasing therapeutic options for this disease.

1. Develop novel in vitro models

We develop patient-near models that will allow us to better study osteosarcoma development and mechanisms of chemoresistance. We focus on patient-derived cell cultures and biomimetic technologies such as organ-on-a-chip.

2. Explore how cellular quiescence mediates chemoresistance

We use functional molecular assays and in vitro models to explore how quiescence, the ability of cells to block proliferation temporarily, enables osteosarcoma cancer cells to avoid the effect of chemotherapy.

3. Identify novel therapeutic combinations using drug screening approaches

We use focused compound screenings to identify potential targets to be used in combination with standard of care treatment.

Group members

Selected publications

1. Usher I, O’Donnell P, Ligammari L … Cottone L and Flanagan AM. The TBXT germline rs2305089 single nucleotide polymorphism is associated with the Benign Notochordal Cell Tumour and chordoma. Journal of Pathology. Accepted.
2. Green D, van Ewijk R, Tirtei E, Andreou D, Baecklund F, Baumhoer D, Bielack SS, Botchu R, Boye K, Brennan B, Capra M, Cottone L, et al. Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement. Clin Cancer Res. 2024 Aug 15;30(16): 3395-3406.
3. Salomoni P, Flanagan AM, Cottone L. (B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer. Cell Death Differ. 2025 Jan;32(1): 66-77.
4. Haefliger S, Bubbear J, Davies C, Cottone L … Flanagan AM. Multifocal osteoclast-rich tumour in Paget bone disease and conventional giant cell tumour, two genetically distinct entities? Sequencing from a single case. Skeletal Radiol. 2024 Jan;53(1): 175-178.
5. Cottone L, Ligammari L, Lee HM … Flanagan AM. Aberrant paracrine signalling for bone remodelling underlies the mutant histone-driven giant cell tumour of bone. Cell Death Differ. 2022 Dec;29(12): 2459-2471.
6. Usher I, Ligammari L, Ahrabi S, Hepburn E, Connolly C, Bond GL, Flanagan AM, Cottone L. Optimizing CRISPR/Cas9 Editing of Repetitive Single Nucleotide Variants. Front Genome Ed. 2022 Jul 5;4: 932434.
7. Zhao T, Siu IM, Williamson T … Cottone L, Flanagan AM, Hann CL, Gallia GL. AZD8055 enhances in vivo efficacy of afatinib in chordomas. J Pathol. 2021 Sep;255(1): 72-83.
8. Cottone L, Cribbs AP, Khandelwal G … Flanagan AM. Inhibition of Histone H3K27 Demethylases Inactivates Brachyury (TBXT) and Promotes Chordoma Cell Death. Cancer Res. 2020 Oct 15;80(20): 4540-4551.
9. Cottone L, Eden N, Usher I … Flanagan AM. Frequent alterations in p16/CDKN2A identified by immunohistochemistry and FISH in chordoma. J Pathol Clin Res. 2020 Apr;6(2):113-123.
10. Amary F, Perez-Casanova L, Ye H, Cottone L, et al. Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement. Mod Pathol. 2019 Dec;32(12): 1762-1771.
11. Scheipl S, Barnard M, Cottone L … Flanagan AM. EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen. J Pathol. 2016 Jul;239(3): 320-34.