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Article
Open AccessIntegrin α11β1 in tumor fibrosis: more than just another cancer-associated fibroblast biomarker?
There is currently an increased interest in understanding the role of the tumor microenvironment (TME) in tumor growth and progression. In this context the role of integrins in cancer-associated fibroblasts (C...
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Article
Open AccessUnsupervised determination of lung tumor margin with widefield polarimetric second-harmonic generation microscopy
The extracellular matrix (ECM) is amongst many tissue components affected by cancer, however, morphological changes of the ECM are not well-understood and thus, often omitted from diagnostic considerations. Po...
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Article
Open AccessIntegrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Only a fraction of NSCLC harbor actionable driver mutations and there is an urgent need for patient-derived model systems tha...
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Role of the Extracellular Matrix in Tumor Stroma: Barrier or Support?
Extensive evidence exists to functionally implicate stromal cancer-associated fibroblasts in tumor progression. Data from experimental cancer models has questioned the exclusive tumor-supportive function of th...
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Article
Open AccessThe Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors
Cancer cells bearing distinct KRAS mutations exhibit variable sensitivity to SHP2 inhibitors (SHP2i). Here we show that cells harboring KRAS Q61H are uniquely resistant to SHP2i, and investigate the underlying...
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Article
PD-L1 as a biomarker of response to immune-checkpoint inhibitors
Immune-checkpoint inhibitors targeting PD-1 or PD-L1 have already substantially improved the outcomes of patients with many types of cancer, although only 20–40% of patients derive benefit from these new thera...
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Article
Open AccessPatient-derived tumor xenograft and organoid models established from resected pancreatic, duodenal and biliary cancers
Patient-derived xenograft (PDX) and their xenograft-derived organoid (XDO) models that recapitulate the genotypic and phenotypic landscape of patient cancers could help to advance research and lead to improved...
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Article
Open AccessChronic obstructive pulmonary disease prevalence and prediction in a high-risk lung cancer screening population
Chronic obstructive pulmonary disease (COPD) is an underdiagnosed condition sharing risk factors with lung cancer. Lung cancer screening may provide an opportunity to improve COPD diagnosis. Using Pan-Canadian...
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Article
Open AccessTowards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor
Esophageal adenocarcinoma has few known recurrent mutations and therefore robust, reliable and reproducible patient-specific models are needed for personalized treatment. Patient-derived organoid culture is a ...
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Article
A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer
Background Resistance to Epidermal Growth Factor inhibition (EGFRi) in patients with KRAS wild-type (wt) Colorectal Cancer (CRC) may occur as a result of PI3K/AKT/mTOR signaling. We conducted a study to establish...
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Article
Open AccessProtein-altering germline mutations implicate novel genes related to lung cancer development
Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We fin...
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Article
A drug discovery platform to identify compounds that inhibit EGFR triple mutants
Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease. Historically, therapeutics targeting RTKs have been identified using in vitro kinase assays...
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Article
Rho guanine nucleotide exchange factor ARHGEF10 is a putative tumor suppressor in pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal human cancers, with 5-year patient survival rates of <5%. Activating mutations in KRAS are the predominant oncogenic drivers of PDAC but are ...
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Article
Open AccessPIDD interaction with KEAP1 as a new mutation-independent mechanism to promote NRF2 stabilization and chemoresistance in NSCLC
Chemotherapy resistance is a major problem in non-small cell lung cancer (NSCLC) treatment. A major mechanism of chemoresistance involves stabilization of the NRF2 transcription factor. NRF2 levels are normall...
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Article
Open AccessTargeting late-stage non-small cell lung cancer with a combination of DNT cellular therapy and PD-1 checkpoint blockade
Though immune checkpoint blockade (ICB) against PD-1 has shown success in the treatment of lung cancer, not all patients respond. We have previously shown that adoptive transfer of double negative T (DNT) cell...
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Article
Open AccessHuman double negative T cells target lung cancer via ligand-dependent mechanisms that can be enhanced by IL-15
The advents of novel immunotherapies have revolutionized the treatment of cancer. Adoptive cellular therapies using chimeric antigen receptor T (CAR-T) cells have achieved remarkable clinical responses in B ce...
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Article
Open AccessONECUT2 is a driver of neuroendocrine prostate cancer
Neuroendocrine prostate cancer (NEPC), a lethal form of the disease, is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, which results in resistance to AR-t...
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Article
Open AccessTyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation
Deregulation of the RAS GTPase cycle due to mutations in the three RAS genes is commonly associated with cancer development. Protein tyrosine phosphatase SHP2 promotes RAF-to-MAPK signaling pathway and is an esse...
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Article
Open AccessFine map** of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
The basis for associations between lung cancer and major histocompatibility complex genes is not completely understood. Here the authors further consider genetic variation within the MHC region in lung cancer ...
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Article
Open AccessIdentification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk
Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chr...
