| First Author | Liu XL | Year | 2018 |
| Journal | Cancer Lett | Volume | 433 |
| Pages | 273-282 | PubMed ID | 30003928 |
| Mgi Jnum | J:264244 | Mgi Id | MGI:6195912 |
| Doi | 10.1016/j.canlet.2018.07.011 | Citation | Liu XL, et al. (2018) Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3Kalpha-selective inhibitor CYH33 in breast cancer. Cancer Lett 433:273-282 |
| abstractText | PI3Ks are frequently hyper-activated in breast cancer and targeting PI3Kalpha has exhibited promising but variable response in preclinical and clinical settings. CYH33 is a novel PI3Kalpha-selective inhibitor in phase I clinical trial. We investigated the efficacy of CYH33 against breast cancer and explored potential predictive biomarkers. CYH33 potently restrained tumor growth in mice bearing human breast cancer cell xenografts and in R26-Pik3ca(H1047R);MMTV-Cre transgenic mice. CYH33 significantly inhibited proliferation of a panel of human breast cancer cells, while diversity in sensitivity has been observed. Cells harboring activating PIK3CA mutation, amplified HER2 were more responsive to CYH33 than their counterparts. Besides, cells in HER2-enriched or luminal subtype were more sensitive to CYH33 than basal-like breast cancer. Sensitivity to CYH33 has been further revealed to be associated with induction of G1 phase arrest and simultaneous inhibition of Akt and ERK. Sensitivity of patient-derived xenograft to CYH33 was also positively correlated with decrease in phosphorylated ERK. Taken together, CYH33 is a promising PI3Kalpha inhibitor for breast cancer treatment and decrease in ERK phosphorylation may indicate its efficacy, which provides useful clues for rational design of the ongoing clinical trials. |
