O. J. Sansom

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.

Oncogenic KRAS cells use Wnt signalling and cell dormancy to override homeostatic cell elimination mechanisms in adult pancreas.

This study shows that oncogenic KRAS cells in the adult pancreas evade elimination by using Wnt signaling and cell dormancy.

A Mutation-driven oncofetal regression fuels phenotypic plasticity in colorectal cancer

This study identifies an oncofetal cell state that contributes to resistance in colorectal cancer and shows that targeting both this state and LGR5+ CSCs is needed for effective treatment.

eIF4A1 is essential for reprogramming the translational landscape of Wnt-driven colorectal cancers

This study shows eIF4A1 is critical for supporting translational demands in Wnt-driven colorectal cancers, while eIF4A2 loss accelerates tumourigenesis, and eFT226 inhibits eIF4A1 function in these models.

ALDH1A3-acetaldehyde metabolism potentiates transcriptionalheterogeneity in melanoma

This study shows ALDH1A3 and ACSS2 coordinate acetaldehyde-acetyl-CoA metabolism with histone acetylation in melanoma, contributing to transcriptional heterogeneity and drug resistance.

KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo

This study shows that wild-type KRAS suppresses tumour growth and metastasis in KRAS mutant colorectal cancer while enhancing resistance to MEK inhibition.

Kras loss of heterozygosity promotes MAPK dependent pancreatic ductal adenocarcinoma and induces therapeutic sensitivity

This study shows that loss of wild-type Kras enhances oncogenic Kras signaling and promotes pancreatic ductal adenocarcinoma, while also increasing sensitivity to MEK1/2 inhibitors.

The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation

The paper shows that eIF4A2, a negative regulator of mRNA translation, promotes ECM deposition to accelerate HCC initiation by influencing integrin-mediated signaling and senescence exit.

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target

This study uses metabolomics to stratify colorectal cancer tissues and identifies adenosylhomocysteinase as a potential therapeutic target.

Mutation-induced phenotypic plasticity drives formation of a pro-metastatic tumour-intrinsic niche

This study identifies mutation-induced phenotypic plasticity as a driver of a pro-metastatic tumour-intrinsic niche in BRAF-mutant colorectal cancer.

Targeting a broad spectrum of KRAS-mutant cancers by hyperactivation-induced cell death

This study identifies SHANK3 as a RAS interactor that limits oncogenic KRAS signaling, and shows that disrupting its interaction with KRAS induces cell death in KRAS-mutant cancers.

Spatially Resolved Transcriptomics Deconvolutes Histological Prognostic Subgroups in Patients with Colorectal Cancer and Synchronous Liver Metastases

This study uses spatial transcriptomics to identify prognostic immune and stromal subgroups in colorectal cancer liver metastases, revealing distinct transcriptomic programs associated with survival outcomes.

Aspirin reprogrammes colorectal cancer cell metabolism and sensitises to glutaminase inhibition

This study shows aspirin reprograms colorectal cancer cell metabolism and increases sensitivity to glutaminase inhibition, suggesting potential for improved metabolic therapies in CRC.

MmCMS: Mouse models' Consensus Molecular Subtypes of colorectal cancer

The paper develops three methods to classify mouse colorectal cancer models into human CMS subtypes, finding that pathway-level classifiers outperform gene-level ones for accurate subtype identification.

β-catenin obstructs γδ T cell immunosurveillance in colon cancer through loss of BTNL expression

This study shows that β-catenin signaling in colon cancer cells reduces BTNL expression, impairing γδ T cell immunosurveillance and promoting tumor progression.

mTORC1 activity is essential for disease progression in chronic lymphocytic leukemia

This study shows that mTORC1 is essential for CLL progression in mice, with rapamycin effectively targeting eEF2 to inhibit proliferation and MCL1 expression.

Biological misinterpretation of transcriptional signatures in tumour samples can unknowingly undermine mechanistic understanding and faithful alignment with preclinical data

The paper shows that transcriptional signatures in tumour samples can be misinterpreted due to stromal influences, affecting alignment with preclinical data.

Loss of BCL-3 sensitises colorectal cancer cells to DNA damage, revealing a role for BCL-3 in double strand break repair by homologous recombination

This study shows that loss of BCL-3 increases DNA damage and reduces homologous recombination in colorectal cancer cells, suggesting BCL-3 as a potential target to enhance DNA damage therapy response.

Maturation, developmental site, and pathology dictate murine neutrophil function

This study identifies Ly6G expression levels as a marker for neutrophil maturation stages and shows spleen-derived neutrophils mature faster with distinct transcriptional profiles.

Rpl24Bst mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K

The paper shows that Rpl24Bst mutation suppresses colorectal cancer by enhancing eEF2 phosphorylation through eEF2K, reducing protein synthesis and tumorigenesis.

The extracellular matrix controls stem cell specification and crypt morphology in the developing and adult gut

This study shows that extracellular matrix components, specifically laminin, control stem cell specification and crypt morphology in the gut, with laminin promoting adult stem cell features and crypt-like structures.

Cyclocreatine suppresses prostate tumorigenesis through dual effects on SAM and creatine metabolism

This study identifies cyclocreatine as a dual-action inhibitor of prostate cancer by blocking the phosphagen system and increasing S-adenosyl methionine levels.

Absent expansion of pericentral hepatocytes and altered physiology in Axin2CreERT2 mice

This study re-evaluates lineage tracing in Axin2CreERT2 mice and reports absence of pericentral hepatocyte expansion and altered Wnt pathway physiology.

Active elimination of intestinal cells drives oncogenic growth in organoids

The paper shows cancer cells in organoids eliminate wild-type cells through apoptosis and JNK signaling, promoting their own growth by forcing cell death and fate change in competing cells.

LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency

This study shows that LRG1 promotes tumor vascular dysfunction and suppresses immunotherapy effectiveness, with its inhibition enhancing therapeutic outcomes in mouse cancer models.

RAL GTPases mediate EGFR-driven intestinal stem cell hyperproliferation and tumourigenesis.

This study shows RAL GTPases activate EGFR/MAPK signaling in intestinal stem cells, promoting proliferation and tumorigenesis, but are independent of oncogenic RAS.

KRASG12D mutant cells are outcompeted by wild type neighbours in adult pancreas in an EPHA2-dependent manner.

This study shows that KRASG12D mutant cells are outcompeted by wild-type cells in the adult pancreas, dependent on EphA2 signaling, leading to tissue clearance and reduced premalignant lesions.

Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer

This study identifies EpCAMlo colon cancer cells with phenotypic plasticity, linking Wnt/β-catenin signaling and EMT activation to metastasis and poor prognosis.

Aspirin-mediated DKK-1 increase rescues Wnt-driven stem-like phenotype in human intestinal organoids

The paper shows aspirin reduces Wnt-driven stem-like traits in intestinal organoids by increasing DKK-1, suggesting a mechanism for its anti-cancer effects.

Non-canonical HIF-1 stabilization is essential for intestinal tumorigenesis

This study shows that non-canonical HIF-1 stabilization is crucial for intestinal tumorigenesis, independent of hypoxia, by affecting both epithelial and microenvironmental oncogenic processes.