Nicholas Hornstein, an Assistant Professor at Northwell Health, recently posted on LinkedIn:
“Conventionally, drug development follows a linear path.
This typically involves: creating the drug, administering it, observing resistance emerge, and then devising subsequent strategies.
However, that’s not the approach Revolution Medicines is taking.
During AACR26, they unveiled RM-055, a truly novel concept.
Even before DaraxONRASib is widely available, they are already developing solutions to anticipated resistance.
Mechanism of action:
- Mutant RAS proteins often exhibit significant resistance to GAP-mediated hydrolysis
- This characteristic maintains RAS in its active conformation
- With RM-055, they have identified a method to boost this hydrolysis
RM-055 demonstrates the ability to:
- re-establish hydrolysis in mutant RAS
- mitigate resistance observed in daraxonrasib-resistant models
- elicit activity even within RAS-amplified contexts
This represents a highly insightful strategy for addressing this therapeutic area.
It moves beyond merely presenting ‘our new inhibitor.’
Instead, it signals: we anticipate resistance to our treatment, so we are proactively developing solutions.
This forward-thinking approach is key to curing cancer, rather than relying on redundant therapies (I truly hope to see fewer new PD1 programs).”
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