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Apr 26, 2026
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Nicholas Hornstein: Anticipating Resistance and Revolution Medicines’ Proactive Strategy for RAS Therapy

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Nicholas Hornstein, Assistant Professor at Northwell Health, shared a post on LinkedIn:

“Drug development is supposed to be linear.

Build the drug – use the drug – resistance shows up – then figure out what to do next.

And not what Revolution Medicines is doing.

At AACR26, they disclosed RM-055, which honestly, is a unique concept.

Before DaraxONRASib is even fully in the world, they’re building around resistance.

How it works:

  • Most mutant RAS proteins are relatively resistant to GAP-mediated hydrolysis
  • That helps keep RAS in the active state
  • They’ve found a way to enhance that hydrolysis with RM-055

RM-055 can:

  • restore hydrolysis in mutant RAS
  • flatten daraxonrasib-resistant models
  • generate activity even in RAS-amplified settings

That’s a very smart way to think about this space.

Not just ‘here’s our inhibitor.’

More like: we already know resistance to our drug is coming, so let’s start building now.

That’s how we cure cancer, not more me-toos (if I hear about another new PD1 program, I’m going to cry).”

Nicholas Hornstein

Other articles featuring Nicholas Hornstein on OncoDaily.

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