Cosper serves as principal investigator on the project, working alongside co-principal investigators Emma Watson, PhD, of UMass Chan Medical School and Jason Sheltzer, PhD, of Stanford University. The three researchers developed the collaboration after meeting through a Chromosomal Instability Workshop that brought together experts in the field.

The project focuses on radioligand therapy (RLT), an emerging form of cancer treatment in which a radioactive isotope is attached to a molecule that selectively binds cancer cells. Lutetium-177, an FDA-approved radionuclide used to treat metastatic prostate cancer and neuroendocrine tumors, has demonstrated significant clinical benefit, yet the biological mechanisms that determine why some patients respond while others develop resistance remain largely unknown.

Building on preliminary studies made possible by a pilot grant from the UW Initiative for Theranostic and Particle Therapy (ITPT) with assistance from the Small Animal Imaging & Radiotherapy Facility (SAIRF), Cosper’s laboratory discovered that Lutetium-177 induces significant chromosome missegregation during cell division, a process known as chromosomal instability. The ASPIRE-funded research will investigate how low levels of ongoing chromosome missegregation may drive the development of treatment resistance by promoting tumor evolution and identify specific genetic alterations that influence sensitivity to radioligand therapy.

Using two innovative libraries representing approximately 2,100 unique oncogenes and cancer-associated mutations, the team will conduct comprehensive analyses aimed at uncovering biomarkers of treatment response and identifying new therapeutic targets. The findings could help improve the effectiveness of radioligand therapies and guide more personalized treatment strategies for patients with cancer.