With the recent clinical approval of sotorasib, the first drug targeting KRASG12C, a milestone was reached in the treatment of lung cancer.
While initial drug response is remarkable, resistance occurs rapidly and most patients relapse. A better understanding of the mechanisms of action involved in the response and the development of resistance to these drugs is required. Interestingly, KRASG12C inhibitors induce profound changes in the expression of genes involved in the modulation of the tumour microenvironment, suggesting an opportunity to tackle the development of resistance by combining these drugs with immunotherapy.
On 3 February 2022, DDW will host a free event Reorganisation of the tumour microenvironment in response to KRASG12C inhibition in a model of lung adenocarcinoma.
It will take place at 2PM GMT, 3PM CET.
Register for free here.
The event will feature the expertise of:
Luca Mazzitelli, Science and Technology Advisor, 10x Genomics, who will discuss resolving complex biology with single cell and spatial multiomics.
Jean-Baptiste Guillerme, who will present on TotalSeq reagents for single cell multiomics and will explain how to uncover unique phenotypes and understand protein and RNA expression on a single-cell level with TotalSeq oligo-conjugated antibodies.
Sophie de Carne, Project Research Scientist, The Francis Crick Institute will discuss the reorganisation of the tumour microenvironment in response to KRASG12C inhibition. She will reveal that to understand the effect of inhibiting oncogenic RAS signalling on the tumour microenvironment, she used an orthotopic mouse model of lung cancer carrying a KrasG12C mutation, the 3LL cell line, and treated 3LL-tumour-bearing mice with MRTX1257. She performed CITE-Seq on these tumours and measured the changes in immune cell representation and the differential gene expression occurring in these immune cells after treatment. It was observed that the profound remodelling of the macrophage compartment after treatment was consistent with what our lab recently published in this model using imaging mass cytometry.