Congrats again to Faith Ryu on the gorgeous cover and our amazing team in the lab (Erik Blomain, Shaghayegh Soudi, Ziwei Wang, Anish Somani, and many more!). Thank you to all of our collaborators and grant support for making this possible! (8/8)

Key takeaway ✅: We think targeting resistant subclones will be critical to improve the response of sarcomas and other cancers to radiotherapy, and we are optimistic that tools like ctDNA analysis can help us identify approaches to help radiation kill these cells. (7/8)

Finally, we demonstrated that circulating tumor DNA can accurately measure subclonal architecture and non-invasively monitor sarcoma evolution during radiotherapy. (6/8)

By analyzing genes mutated in radiosensitive subclones that contracted during radiotherapy, we observed an enrichment in mutations affecting the calcium signaling pathway. Inhibiting calcium transporters made sarcoma cells more sensitive to radiotherapy. (5/8)

Using metrics of genetic divergence between regions to measure selection pressure, we found that radiotherapy increased evolutionary selection and led to the expansion of resistant subclonal cancer cells. (4/8)

We observed evidence of strong selection during sarcoma development with most untreated UPS displaying initial linear evolution followed by branching evolution later in tumor development. (3/8)

We performed spatial and temporal genomic profiling of undifferentiated pleomorphic sarcomas (UPS) treated with or without radiotherapy to study sarcoma evolution. (2/8) aacrjournals.org/cancerres/ar...