Citations 3
Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force
Pacenta, Holly , Allen‐Rhoades, Wendy , Langenau, David M. , Houghton, Peter J. , Keller, Charles , Heske, Christine M. , Deel, Michael D. , Linardic, Corinne M. , Stewart, Elizabeth , Turpin, Brian , Harrison, Douglas J. , Khan, Javed , Mascarenhas, Leo , Skapek, Stephen X. , Meyer, William H. , Hawkins, Douglas S. , Hingorani, Pooja , Laetsch, Theodore W. , Mascarenhas, Leo , Skapek, Stephen X , Laetsch, Theodore W , Hawkins, Douglas S , Allen-Rhoades, Wendy A , Shern, Jack F. , Chen, Eleanor Y. , Amatruda, James F. , Linardic, Corinne M
Journal of Clinical Medicine | April 1, 2021 | Volume: 10 | Issue: 7 | Pages: 1416
Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children’s Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. The task force was comprised of clinicians and basic scientists who collectively identified new agents for evaluation and prioritization in clinical trial testing. Here, we report the work of the task force including the framework upon which the decisions were rendered and review the top classes of agents that were discussed. Representative agents include poly-ADP-ribose polymerase (PARP) inhibitors in combination with cytotoxic agents, mitogen-activated protein kinase (MEK) inhibitors in combination with type 1 insulin-like growth factor receptor (IGFR1) inhibitors, histone deacetylase (HDAC) inhibitors, and novel cytotoxic agents.
Author response: tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish
Hayes, Madeline N. , Moore, Finola E., Tang, Qin , Blackburn, Patrick R. , Ramakrishnan, Ashwin , Reeder, Sophia M. , Nielsen, G. Petur , Hasserjian, Robert P. , Langenau, David M. , Ignatius, Myron S. , Garcia, Sara P. , Baxi, Kunal , Wang, Long, Jin, Alexander , Chen, Yidong , Chen, Eleanor Y. , Tirode, Franck , Ekker, Stephen C.
No container title available | September 7, 2018 | Volume: No volume available | Issue: No issue available | Pages: No page available
tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish
Hayes, Madeline N. , Moore, Finola E., Tang, Qin , Blackburn, Patrick R. , Baxi, Kunal , Wang, Long , Jin, Alexander , Ramakrishnan, Ashwin , Reeder, Sophia M. , Nielsen, G. Petur , Hasserjian, Robert P. , Tirode, Franck , Ekker, Stephen C. , Langenau, David M. , Tang, Qin , Blackburn, Patrick , Tirode, Franck , Ekker, Stephen C , Langenau, David M , Ignatius, Myron S. , Garcia, Sara P. , Chen, Yidong , Chen, Eleanor Y.
eLife | September 7, 2018 | Volume: 7 | Issue: No issue available | Pages: No page available
The TP53 tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni patients with germ line inactivation are predisposed to developing cancer. Here, we generated tp53 deleted zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive Natural Killer cell-like leukemia for which no animal model has been developed. Because the tp53 deletion was generated in syngeneic zebrafish, engraftment of fluorescent-labeled tumors could be dynamically visualized over time. Importantly, engrafted tumors shared gene expression signatures with predicted cells of origin in human tissue. Finally, we showed that tp53del/del enhanced invasion and metastasis in kRASG12D-induced embryonal rhabdomyosarcoma (ERMS), but did not alter the overall frequency of cancer stem cells, suggesting novel pro-metastatic roles for TP53 loss-of-function in human muscle tumors. In summary, we have developed a Li-Fraumeni zebrafish model that is amenable to large-scale transplantation and direct visualization of tumor growth in live animals.