NOTCH4 and hepatocellular carcinoma: NOTCH1,42 NOTCH3,43 and NOTCH4 (ref. 37) have all been associated with poor prognosis in HCC, including larger tumor size and metastasis, although one study suggests a dominant role for NOTCH1 over NOTCH3.42 Other evidence suggests that blocking NOTCH signaling in liver cancer cells using a pan-NOTCH γ-secretase inhibitor suppresses cell proliferation, and this appears to be independent of NOTCH1 dysregulation.36 Further evidence suggests that NOTCH2 on its own can drive HCC growth in human and mouse models of HCC and in patients.43,44