Andrew J. Aguirre

KRASG12C Inhibition Remodels the Non-Small Cell Lung Cancer Surfaceome to Uncover Targetable Vulnerabilities

This study shows that KRASG12C inhibitors alter the surface proteome of lung cancer cells, revealing FOLR1 as a new target when combined with an antibody drug conjugate.

KRAS inhibition drives adaptive surfaceome remodeling and reveals ALPP/ALPPL2 as a targetable vulnerability in pancreatic cancer

This study identifies ALPP/ALPPL2 as a targetable vulnerability in pancreatic cancer by analyzing proteomic changes induced by KRAS inhibition and developing an antibody drug conjugate.

Context-specific genetic interaction mapping reveals combinatorial KRAS/FGFR dependence in pancreatic cancer

The paper identifies combinatorial KRAS/FGFR dependence in pancreatic cancer through genetic interaction mapping and shows that combined inhibition overcomes resistance.

De novo design of protease-activatable cytokine prodrugs

This study designs protease-activatable cytokine prodrugs to reduce toxicity while maintaining antitumor efficacy in tumor models.

Tumor-tropic E. coli engineered as living T and NK cell engagers

This paper develops LIME, a bacterial platform that engagers T and NK cells to target tumors, showing enhanced cytotoxicity and immune response in preclinical models.

GLIS3 Marks a Neural-like Progenitor Cell State that Drives Metastasis in Pancreatic Ductal Adenocarcinoma

This study identifies Glis3 as a key transcription factor driving metastasis in PDAC by promoting a neural-like progenitor cell state.

Characterization and therapeutic suppression of KEAP1-NRF2-driven resistance to KRAS inhibitors in pancreatic and lung cancer

This study identifies KEAP1 loss as a resistance mechanism to KRAS inhibitors in pancreatic and lung cancer and shows that combining glutamine inhibition with KRAS inhibitors can overcome this resistance.

Integrated inference of cancer gene expression from cell-free plasma chromatin

APEX infers cancer gene expression from plasma cfChIP-seq data, outperforming existing methods and enabling subtype classification and biomarker identification.

Cancers modulate p53 truncal neoantigen display to evade T cell detection

This study identifies that cancers limit p53 neoantigen display on MHC molecules, evading T cell detection through immune selection and ERAP1-mediated destruction.

VEGFR2 blockade overcomes acquired KRAS G12D inhibitor resistance driven by PI3Kγ activation

This paper identifies VEGFA-VEGFR2 signaling driven by PI3Kγ activation as a mechanism of acquired resistance to KRAS G12D inhibitors and shows that blocking this pathway restores drug sensitivity in resistant cancer models.

De novo pyrimidine biosynthesis inhibition synergizes with BCL-XL targeting in pancreatic cancer

This study identifies that combining DHODH inhibition with BCL-XL targeting synergistically induces apoptosis in pancreatic cancer, offering a new combination therapy strategy.

Cell states and neighborhoods in distinct clinical stages of primary and metastatic esophageal adenocarcinoma

The paper analyzes multiomic data from primary and metastatic esophageal adenocarcinoma tumors to identify cell states and their spatial interactions, linking them to clinical outcomes.

Comprehensive structure-function analysis reveals gain- and loss-of-function mechanisms impacting oncogenic KRAS activity

This study uses deep mutational scanning to analyze KRAS variants, identifying gain- and loss-of-function mechanisms and their impact on oncogenic activity.

Defining protein variant functions using high-complexity mutagenesis libraries and enhanced mutant detection software ASMv1.0

The paper introduces a method to screen large variant libraries with mutations across wide regions using improved mutant detection software, enabling accurate variant calling and counting from sequencing data.

Massively parallel phenotyping of variant impact in cancer with Perturb-seq reveals a shift in the spectrum of cell states induced by somatic mutations

The paper uses Perturb-seq to assess the phenotypic impact of somatic variants in cancer, revealing a continuum of gain-of-function KRAS variants.

Single-nucleus and spatial transcriptomics of archival pancreatic cancer reveals multi-compartment reprogramming after neoadjuvant treatment

This study uses single-nucleus and spatial transcriptomics to analyze pancreatic cancer before and after neoadjuvant treatment, revealing changes in cell states and immune infiltration that may inform therapy.

The enteric nervous system of the human and mouse colon at a single-cell resolution

The paper profiles the enteric nervous system of human and mouse colon at single-cell resolution, revealing diverse neuron subsets and shared transcriptional programs between species.