Ibrahim Halil Sahin: Our article on KRAS targeting approaches for patients with CRC is now out
Ibrahim Halil Sahin, Assistant Professor at UPMC Hillman Cancer Center, shared a post on X/Twitter:
“Our article on KRAS targeting approaches for patients with CRC is now out
In this exciting article we summarized the recent progress which resulted in practice changing outcomes and elaborated on future opportunities
Here are some key points below.
KRAS G12C is a specific mutation in which glycine is mutated into cysteine and this aa change opened paths for the drug development with covalent inhibitors due to sulfate molecule in cysteine aa
KRAS G12C has also other intrinsic characteristics allowed to develop drugs to lock it in its inactive form
Currently there are several G12C inhibitors in development most of which will likely make it to bedside
Most common resistance mechanisms to G12C inhibitors include secondary MAPK and RTK alterations such as other KRAS mutations
Although initial thought was that we can only have effective KRAS inhibitors with covalent inhibitors, there are research suggesting otherwise and removal of covalent warheads of G12C inhibitors revealed biological effective panKRAS and PanRAS inhibitors
Most of panKRAS and panRAS inhibitors do not form covalent bonds
Unlike several other disease, use of EGFR blockade is quite critical for KRAS targeting and also for all EGFR downstream inhibitors given rebound activation of EGFR when its downstream is inhibited (we learned this from BRAF as well)
Targeting RAS oncogenes will allow us to create more therapeutic approaches and strategies.
There is more hope in our horizon than it was ever before. Progress will continue to evolve to change the course of cancer”
Source: Ibrahim Halil Sahin/X
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