KRAS / RAS targeting: from platform to Phase 3
First-generation G12C drugs (sotorasib, adagrasib) bind KRAS in the off state. After treatment, RTK feedback reloads KRAS into the on state.
KRAS is essentially a molecular switch that bounces between an active GTP-bound state and an inactive GDP-bound state. G12C inhibition works when it traps KRAS in its off state; binding by an inhibitor is irreversible; we have already seen emergence of resistance. #AACR26 3/x https://t.co/33fl3Hf4xN
Heat 8 · 6 likes · 1 reply · 1 repost
Kayla Tyskiewicz, Markus Hippich, Tristan Cates, Gervaise Henry, Gilad Silberberg, Nicole Spanburg, Madeline Westcott, Daniel Ciznadija, Michael Boice, Paul Heverly, Frank Smith, Marianna Zipeto, Stefano Cairo, Sebastian Brabetz
Read the abstract →Seema nadir, Sumaiya Binte Hamid, Mati Ur Rehman, Azhar Hussain Rajabali, Kulsoom K. Ghias, Arooj Shafiq
Read the abstract →Silvia Coma, Ian Smith, Cristina Caffarra Malvezzi, Clint A. Stalnecker, Emilia Berardelli, Enrico Patrucco, Fusheng Zhou, Channing Der, Chiara Ambrogio, David G. DeNardo, Jonathan A. Pachter
Read the abstract →Ahmad A. Tarhini, Monica Chen, Jia Liu, Varun Monga, Victoria Atkinson, Sarina A. Piha-Paul, Bartosz Chmielowski, Benjamin Herzberg, Charlotte Lemech, Prachi Bhave, Ganessan Kichenadasse, Gerald Falchook, Janice Mehnert, Andrae Vandross, Mohamad Salkeni, Meredith McKean, David Wages, Ann Marie Kennedy, Meagan B. Ryan, John Clark, Abdulaziz Nanah, Michael J. Fossler, Philip Komarnitsky, Igor Puzanov
Read the abstract →Kanwal Pratap Raghav, Jun Zhang, Myung-Ah Lee, Jingdong Zhang, John Park, Yanqiao Zhang, Susana Rosello Keranen, Byoung Chul Cho, Herbert Ho Fung Loong, Cheng Chen, Huan Li, Shaonan Wang, Yandong Shen, Zifei Fan, Qian Chen, Hui Wang, Jing Zhang, George Zhi Jian Chen, Jayesh Desai, Antoine Hollebecque
Read the abstract →Source: x.com · x.com