J. Downward

Imaging of MAP kinase dynamics reveals endocytic regulation of pulsatile signalling and network re-wiring in response to targeted therapy in EGFR-mutant non-small cell lung cancer

The paper uses single-cell imaging to show that drug-tolerant cells in EGFR-mutant lung cancer rewired ERK signaling through endocytic pathways and adhesion complexes, driven by YAP and PTPRS.

Spatial proteomic analysis of a lung cancer model reveals regulatory T cells attenuate KRAS-G12C inhibitor-induced immune responses

The paper identifies regulatory T cells as mediators of resistance to KRAS-G12C inhibitors and anti-PD-1 therapy through spatial proteomic analysis of lung cancer models.

A targetable PREX2/RAC1/PI3Kβ signalling axis confers resistance to clinically relevant therapeutic approaches in melanoma

This study identifies a druggable PREX2/RAC1/PI3Kβ signalling axis in BRAF-mutant melanoma that confers resistance to therapies and can be targeted to improve treatment outcomes.

Combining RASG12C(ON) inhibitor with SHP2 inhibition sensitises immune excluded lung tumours to immune checkpoint blockade: a strategy for turning cold tumours hot

This paper shows that combining RASG12C(ON) and SHP2 inhibitors can make cold lung tumors responsive to immune checkpoint blockade by altering the tumor microenvironment and enhancing anti-tumor immunity.

CRISPR/Cas9 screen identifies KRAS-induced COX-2 as a driver of immunotherapy resistance in lung cancer

The paper identifies KRAS-induced COX-2 as a driver of immunotherapy resistance in lung cancer through CRISPR/Cas9 screening and shows targeting COX-2 enhances immune checkpoint blockade efficacy.

Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis

This study identifies ZDHHC20 as a palmitoyl transferase promoting pancreatic cancer metastasis by affecting tumor-immune interactions, with no effect on proliferation or primary tumor growth.

Therapeutic KRASG12C inhibition drives effective interferon-mediated anti-tumour immunity in immunogenic lung cancers

KRASG12C inhibition enhances anti-tumour immunity in immunogenic lung cancers by upregulating interferon signaling through Myc repression, but only synergizes with immune checkpoint blockade in highly immunogenic models.

Oncogenic RAS activity predicts response to chemotherapy and outcome in lung adenocarcinoma

This study develops a transcriptional signature to measure RAS pathway activity in lung adenocarcinoma, showing it better predicts chemotherapy response and prognosis than KRAS mutation status.

Characterisation of tumour immune microenvironment remodelling following oncogene inhibition in preclinical studies using an optimised imaging mass cytometry workflow

The paper optimises an imaging mass cytometry workflow to study TME remodelling in mouse models after KRAS G12C inhibitor treatment.

An immunogenic model of KRAS-mutant lung cancer for study of targeted therapy and immunotherapy combinations

This paper develops an immunogenic mouse model of KRAS-mutant lung cancer that responds to immunotherapy and reveals immune responses target endogenous retroviral antigens rather than neoantigens.