BioCentury
ARTICLE | Distillery Therapeutics

Cancer

July 10, 2018 9:38 PM UTC

Patient sample and cell culture studies suggest promoting IGFBP5 expression or inhibiting POU2F3 or IGF1R could help treat POU2F3-expressing small cell lung cancer (SCLC). In tumor samples from SCLC patients, levels of IGF1R were higher, and levels of its negative regulator IGFBP5 were lower, in tumors expressing high levels of POU2F3 than in tumors expressing low levels of POU2F3. In human SCLC cell lines, cells expressing high levels of POU2F3 were more sensitive to a tool compound IGF1R inhibitor than cells expressing low levels of POU2F3. In four of the cell lines expressing high levels of POU2F3, shRNA-mediated knockdown of POU2F3 decreased proliferation compared with a non-specific shRNA, and in two of the cell lines, overexpression of IGFBP5 decreased proliferation compared with normal IGFBP5 expression. Next steps could include testing POU2F3 inhibition in animal models of POU2F3-expressing SCLC.

Amgen Inc., NantWorks LLC and Takeda Pharmaceutical Co. Ltd. have ganitumab (AMG 479), a mAb antagonist of IGF1R, in Phase III testing to treat sarcoma and Phase II testing to treat colorectal cancer, ovarian cancer and solid tumors...