Colin Lindsay, Clinical Senior Lecturer in Thoracic Oncology at The University of Manchester, shared a post on LinkedIn:
“We have been working on this new Cancer Discovery report for a few years.
So delighted to see the hard work of many team members rewarded, particularly Will McDaid and Helen Adderley who have done nothing but demonstrate endless graft together (apart from when Avril Lavigne was on).
Many amazing external academic collaborators to thank – Sophie de Carne, Phil East, Mihaela Aldea, Benjamin Besse, Heather Wakelee, Ernest Nadal, Sonia Castillo Lluva and all at the French IFCT team.
If you want to know as much as there is to know about translation of KRAS codon 13 towards clinical gain in the lung cancer clinic, then please take a look:
- NSCLC with codon 13 (particularly G13C) relies on common co-mutations to accelerate its ‘oncopotency’ but codon 13 changes are sufficient for transformation.
- These co-mutations likely offset some of the immune checkpoint blockade benefit that is typically associated with higher PD-L1 and TMB disease.
- We use a unique (ON)-state KRAS G13C inhibitor, RMC-8839, demonstrating its activity across isogenic/initiation and advanced models of NSCLC.
- We highlight that G13C has a particular vulnerability to common chemotherapies, showing combination synergy with RMC-8839 in an in vivo setting.
Having the opportunity to work so closely with Revolution Medicines for this report has been an endless education – massive thanks to Kyle Seamon, Matthew Holderfield, Jan Smith and Mallika Singh for all their interest in our program. If you want to know every biochemical update about RMC-8839 and also other rarer KRAS mutants, please take a look at their manuscript that is out now in the same issue of Cancer Discovery.
Last thing is to mention is that this project started with a clinical observation – that KRAS codon 13 mutations frequently co-mutate with NF1 – underlining that we would be nowhere without the interest and commitment of our patients in research and clinical trials. In the last week I have seen those affected by codon 13 who are still struggling – we’ll not be complacent and continue to push forward at every opportunity.”
Title: Targeting KRAS codon 13 mutations using direct combination approaches in non-small cell lung cancer
Authors: William J. McDaid, Helen Adderley, Paolo D. d’Arienzo, Ana Sofia Parreira, Laura C. Woodhouse, Yongxian Zhuang, Sonia Castillo-Lluva, Kirsten L. Tinsley, James Cooksedge, Martin J. Baker, Joshua Searle, Katherine D. Brown, Mathew Carter, Mihaela Aldea, Arianna Marinello, Jacqueline V. Aredo, Nadia Gomez Serra, Maria Bisbe, Philip East, Sophie de Carné Trécesson, Fabrice Barlesi, Marie Wislez, Benjamin Besse, Heather A. Wakelee, Ernest Nadal, Fiona Blackhall, David C. Wedge, Matthew Holderfield, Jacqueline A. M. Smith, Mallika Singh, Kyle J. Seamon, Angeliki Malliri, Colin R. Lindsay
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