Empowered Patient Podcast Using Targeted Pan-RAS Inhibitors to Fight RAS-Driven Cancers with Dr. Tariq Arshad Qualigen Therapeutics
Dr. Tariq Arshad is the Senior Vice President and Chief Medical Officer at Qualigen Therapeutics, addressing multiple types of RAS-driven cancers. While researchers understand RAS's role in tumorgenesis and have identified which cancers are RAS-driven, RAS has been considered an undruggable target. With a pan-RAS approach inhibiting KRAS, HRAS and NRAS, the three isoforms of RAS, Qualigen is identifying drug candidates showing strong anti-tumor efficacy.
Tariq elaborates, "That was so difficult to do because when you look at the KRAS protein itself, it's a complicated, three-dimensional structure that constantly changes. The opening, or the aperture, where a small molecule can attach and inhibit the G12C moiety or specifically the cysteine amino acid, which is targeted by these inhibitors, it appears for a very, very short period of time. It's nothing short of a miracle of bioengineering, and specifically medicinal chemistry that we've been able to identify these inhibitors that can target that subcomponent, that very small aperture within the overall KRAS protein, without, as you're saying, impacting the function of the overall protein."
"The field is moving towards understanding why this lack of durability exists and is trying to understand whether it's due to the emergence of other mutations, whether it's due to the emergence of wild-type RAS, or whether it's due to other factors. One of the theories that is emerging behind the emergence of this KRAS resistance is the fact that there are other RAS isoforms that exist in the same tumor. They allow a mechanism in which the tumorigenesis can bypass KRAS, even though it's inhibited, and signal into the cell to convert it into a cancer cell. It now becomes important for us to understand how we can address that potential mechanism of resistance."
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