Hiromichi Ebi

Sep 16, 2024 | nature.com | Yoshiaki Nakamura |Jun Watanabe |Naoya Akazawa |Kozo Kataoka |Yoshinori Kagawa |Kun-Huei Yeh | +10 more

AbstractThe interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC).

Jul 18, 2024 | nature.com | Hidenori Kitai |Yu Yang |Rui Yamaguchi |Hiromichi Ebi |David Wildes |Mallika Singh | +1 more

AbstractCurrent KRASG12C (OFF) inhibitors that target inactive GDP-bound KRASG12C cause responses in less than half of patients and these responses are not durable. A class of RASG12C (ON) inhibitors that targets active GTP-bound KRASG12C blocks ERK signaling more potently than the inactive-state inhibitors. Sensitivity to either class of agents is strongly correlated with inhibition of mTORC1 activity.

Dec 14, 2023 | nature.com | Yuta Adachi |Nicola J Armstrong |Stephanie Claire Bridgeman |Tuan Zea Tan |Jean Paul Thiery |Hiromichi Ebi | +1 more

AbstractDespite the promising antitumor activity of SHP2 inhibitors in RAS-dependent tumours, overall responses have been limited by their narrow therapeutic window. Like with all MAPK pathway inhibitors, this is likely the result of compensatory pathway activation mechanisms. However, the underlying mechanisms of resistance to SHP2 inhibition remain unknown. The E3 ligase SMURF2 limits TGFβ activity by ubiquitinating and targeting the TGFβ receptor for proteosome degradation.