iFIT & TüCAD2 Joint Seminar Lecture with Mallika Singh, PhD
Targeting the oncogenic state of RAS with tri-complex inhibitors
on behalf of the iFIT spokespersons and TüCAD2 spokesperson, it is our pleasure to inform you about and invite you to the Joint Seminar Lecture that will take place
on Tuesday, October 22nd at 12:30 pm (CEST)
at Big Lecture Hall in the ENT Clinic (HNO Klinik, Elfriede-Aulhorn-Straße 5 , 72076 Tübingen).
Our guest speaker, Mallika Singh, PhD (Revolution Medicines, Redwood City, USA) will give a talk on
“Targeting the oncogenic state of RAS with tri-complex inhibitors”.
KRAS oncogenic driver mutations occur in approximately 30% of all human cancers, and most frequently in pancreas, colon and lung tumors. Small molecule inhibitors that selectively target the inactive, GDP-bound state of KRAS G12C mutant proteins have demonstrated clinical efficacy in NSCLC as monotherapies albeit almost all treated patients relapse, highlighting an unmet medical need for improved outcomes for this patient population. Furthermore, there are no currently approved RAS-targeted therapy options for the majority of patients with non-G12C RAS mutant cancer, in particular patients with PDAC where over 90% have RAS mutant tumors.
Mallika Singh and her team have designed a series of tri-complex inhibitors that specifically target the GTP-bound, active state of RAS (RAS(ON)). These small molecule inhibitors bind non-covalently to an abundant intracellular protein, cyclophilin A (CypA). The resulting binary complex selectively engages RAS(ON), forming a tri-complex that sterically inhibits RAS interaction with downstream effectors. Her team has generated mutant-selective inhibitors that covalently engage RAS(ON) G12C (RMC-6291) or RAS(ON) G12D (RMC-9805). In addition, RMC-6236 is a RAS(ON) multi-selective inhibitor that non-covalently inhibits the active, GTP-bound state of mutant and wild-type variants of the canonical RAS isoforms (KRAS, NRAS, and HRAS). She will describe the mechanism of action of these investigational agents and the preclinical profiles that support their clinical evaluation in RAS-addicted cancers as monotherapies and combination therapy regimens as RAS(ON) inhibitor doublets.
As a special feature of this program, the iFIT will sponsor free lunch packages! (First come, first serve)
All members of the University Hospital and University of Tübingen are invited to participate!
We look forward to this Seminar Series session and to see you there!
