PTEN deficiency confers colorectal cancer cell resistance to dual inhibitors of FLT3 and aurora kinase A

PTEN is a tumor suppressor found mutated in many cancers. From a synthetic lethality drug screen with PTEN-isogenic colorectal cancer cells, we found that mutant-PTEN cells were resistant to dual inhibitors of FLT3 and aurora kinase-A, including KW2449 and ENMD-2076. KW2449 significantly reduced the viability of wildtype-PTEN cells causing apoptosis, while little effect was observed in mutant-PTEN counterparts. Transcriptome profiling showed that members of PI3K-AKT signaling pathway were strongly changed in cells after KW2449 treatment, indicating a potential role of the pathway in drug resistance.

Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Yifan Liu, Eun Ju Yang, Baoyuan Zhang, Zhengqiang Miao, Changjie Wu, Junfang Lyu, Kaeling Tan, Terence Chuen Wai Poon, Joong Sup Shim Tags: Original Articles Source Type: research