Cancer
Cell culture and mouse studies suggest jointly inhibiting PI3K and either PIM2, TACC1, ZAK, ZFR or ZNF565 could help treat breast cancer. An shRNA screen in a human breast cancer cell line treated with a pan-PI3K inhibitor tool compound identified five genes -- PIM2, TACC1, ZAK, ZFR and ZNF565 -- whose knockdown increased apoptosis compared with control shRNA. In a xenograft mouse model of breast cancer, intratumoral delivery of the PI3K inhibitor plus siRNAs targeting PIM2, TACC1, ZAK, ZFR or ZNF565 decreased tumor cell viability compared with the inhibitor plus an off-target siRNA, or vehicle plus any of the five targeted siRNAs. Also in the model, intratumoral delivery of the PI3K inhibitor plus either of two ZAK inhibitor tool compounds increased tumor cell apoptosis compared with either ZAK inhibitor alone. Next steps include identifying and testing new PIM2, TACC1, ZAK, ZFR, ZNF565 and/or PI3K inhibitors.
Jasco Pharmaceuticals LLC has JP-11646, an oral PIM2 inhibitor, in preclinical testing to treat multiple myeloma (MM)...