Pre-Conference Workshop Day

Workshop A

Approaching the Use of Biologics for RAS Isoform Selective Inhibition

Tuesday 23 February: 10:30-12:00

Mutant RAS signalling is a main cause of cancer. The protein-protein interaction (PPI) of mutant RAS proteins in cancer have been validated as a target for drugging but PPIs are hard to drug, causing an additional level of difficulty in attenuating mutant RAS. Biologics, such as macromolecules like intracellular antibody fragments, provide a molecular biology alternative to conventional RAS drugs because they can attain high affinity, isoform-selectivity and can be potent PPI inhibitors. They can also can be engineered to carry warheads that can activate endogenous cellular processes such as proteasomal degradation that can selectively remove RAS isoforms. Through advancing method for delivery biologics (macrodrugs) to cancer cells, we can provide a new approach to therapy of mutant RAS
expressing cancers.

Topics to be covered

  • What kind of biologics can be used to interfere with mutant RAS function?
  • Comparison of RAS-effector protein-protein interaction inhibition using biologics or using compounds
  • Addition of degrader warheads on anti-RAS biologics to induce mutant RAS degradation and comparison to PROTAC
  • How can we achieve delivery of biologics (macrodrugs) to cancers?

Workshop Leaders

Terry Rabbits Institute of Cancer Research

Terry Rabbits
Professor of Molecular Immunology
Institute of Cancer Research London

12:00-13:00 Morning Break and Virtual Networking

Workshop B

Exploring Preclinical Translation for Targeted Therapies Against KRAS Mutant Tumours

Tuesday 23 February: 13:00-14:30

With the RAS community making continual and important progression, it is vital to consider how we can advance our KRAS/MAPK targets beyond preclinical phases, in order to provide an optimal therapy against cancers. As such, we must outline necessary considerations and rational approaches to streamline progression of effective and safe candidates through the clinic.

Topics to be covered

  • How does resistance to MAPK pathway inhibitors arise in KRAS mutant tumors, and how can we take it into account while translating targeted therapies to the clinic?
  • How can we better identify rational drug combinations to overcome resistance to single target therapies?
  • Exploring the real-world case study of the advancement of combining SHP2 & ERK inhibitors beyond preclinical
  • How can preclinical stage studies be optimised to streamline the progression into clinic?

Workshop Leaders

Sara Mainardi

Sara Mainardi
Senior Postdoctoral Fellow
Netherlands Cancer Institute

14:30-15:30 Afternoon Break

Workshop C

From NMR to Cyro-EM – Exploring Imaging Techniques Essential to RAS Progression

Tuesday 23 February: 15:30-17:00

Despite multiple advances in the field of Ras biology propelled by technological innovations, there are still important lessons to learn when it comes to the structure and dynamics of RAS, but also the biophysical and biochemical properties of complex protein-protein interactions that drive signal transduction. As such, conventional imaging approaches do not suffice to aid the progression and success of RAS targeted therapies. Multiple imaging and spectroscopic approaches and techniques, explored and combined, are essential to understand this complex protein fully, and ensure preclinical candidates make it to the clinic.

Topics to be covered

  • Outlining the landscape of conventional imaging approaches and exploring the potential limitations of using these in preclinical phases
  • How can we harness NMR to investigate molecular interactions and Optimise RAS targeted therapies?
  • How can we use multiple techniques to understand the biophysical and biochemical properties of RAS?
  • Discussing the utility of Cryo-EM technology, its future potentials and possible limitations

Workshop Leaders

Vadim Gaponenko Univeristy of Illinois

Vadim Gaponeko
Professor in the Department of Biochemistry & Molecular Genetics
University of Illinois at Chicago