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View article: Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer
Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer Open
Xevinapant is an orally bioavailable antagonist of select members of the inhibitor of apoptosis protein family. Despite promising phase II data, combining xevinapant with chemoradiotherapy (CRT) failed to improve outcomes in the phase III …
View article: The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models
The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models Open
Reovirus type 3 Dearing (RT3D) is an oncolytic, double-stranded RNA virus. To identify potential RT3D drug-viral sensitizer, here we use a high-throughput screen of therapeutic agents and find a PARP-1 inhibitor, talazoparib, as a top hit.…
View article: Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion
Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion Open
Cytoplasmic pattern recognition receptors (PRR) for double-stranded RNA, such as RIG-I/MDA5, are key mediators of anti-viral responses. Here we screen for synergistic drug-virotherapy combinations and find that the reovirus type III Dearin…
View article: PBRM1 directs PBAF to pericentromeres and protects centromere integrity
PBRM1 directs PBAF to pericentromeres and protects centromere integrity Open
The specialised structure of the centromere is critical for effective chromosome segregation, but its repetitive nature makes it vulnerable to rearrangements. Centromere fragility can drive tumorigenesis, but protective mechanisms preventi…
View article: Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy
Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy Open
The combination of radiotherapy/chemoradiotherapy and immune checkpoint blockade can result in poor outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Here, we show that combining ATR inhibition (ATRi…
View article: Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T-cell receptor signalling
Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T-cell receptor signalling Open
Background Over the past decade, cancer immunotherapies have revolutionized the treatment of melanoma; however, responses vary across patient populations. Recently, baseline tumor size has been identified as an independent prognostic facto…
View article: PBRM1 directs PBAF to pericentromeres and protects centromere integrity
PBRM1 directs PBAF to pericentromeres and protects centromere integrity Open
The specialised structure of the centromere is critical for effective chromosome segregation, but its repetitive nature makes it vulnerable to rearrangements. Centromere fragility can drive tumorigenesis, but protective mechanisms preventi…
View article: Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T cell receptor signalling
Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T cell receptor signalling Open
Background Over the past decade, cancer immunotherapies have revolutionised the treatment of melanoma; however, responses vary across patient populations. Recently, baseline tumour size has been identified as an independent prognostic fact…
View article: PARP inhibitors enhance reovirus-mediated cell killing through the death-inducing signaling complex (DISC) with an associated NF-κB-regulated immune response
PARP inhibitors enhance reovirus-mediated cell killing through the death-inducing signaling complex (DISC) with an associated NF-κB-regulated immune response Open
Oncolytic Reovirus type 3 Dearing (RT3D), is a naturally occurring double-stranded (ds) RNA virus that is under development as an oncolytic immunotherapy We used an unbiased high-throughput cytotoxicity screen of different targeted therape…
View article: Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent anti-PD-L1- and anti-NKG2A-based adjuvant immunotherapy
Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent anti-PD-L1- and anti-NKG2A-based adjuvant immunotherapy Open
Despite some success in other cancer types, the results of combining radiotherapy/chemoradiotherapy and immune checkpoint blockade have been disappointing in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). For…
View article: Supplementary Figures 1-5 and Supplementary Table 1 from Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma
Supplementary Figures 1-5 and Supplementary Table 1 from Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma Open
Supplementary Figure 1 Growth kinetics for all 786-0 xenografts included in the analysis from Figure 1; Supplementary Figure 2 Details of the in vitro angiogenesis assay; Supplementary Figure 3 Isolation of a sunitinib-refractory sub-line …
View article: Data from Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma
Data from Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma Open
Sunitinib and pazopanib are antiangiogenic tyrosine kinase inhibitors (TKI) used to treat metastatic renal cell carcinoma (RCC). However, the ability of these drugs to extend progression-free and overall survival in this patient population…
View article: Data from Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma
Data from Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma Open
Sunitinib and pazopanib are antiangiogenic tyrosine kinase inhibitors (TKI) used to treat metastatic renal cell carcinoma (RCC). However, the ability of these drugs to extend progression-free and overall survival in this patient population…
View article: Supplementary Figures 1-5 and Supplementary Table 1 from Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma
Supplementary Figures 1-5 and Supplementary Table 1 from Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma Open
Supplementary Figure 1 Growth kinetics for all 786-0 xenografts included in the analysis from Figure 1; Supplementary Figure 2 Details of the in vitro angiogenesis assay; Supplementary Figure 3 Isolation of a sunitinib-refractory sub-line …
View article: Data from ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment
Data from ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment Open
Purpose:ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the tumor microenvironmen…
View article: Data from ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment
Data from ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment Open
Purpose:ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the tumor microenvironmen…
View article: Supplementary Data from ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment
Supplementary Data from ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment Open
Supplementary figures and tables
View article: Supplementary Data from ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment
Supplementary Data from ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment Open
Supplementary figures and tables
View article: CDK4/6 inhibition and dsRNA sensor agonism co-operate to enhance anti-cancer effects through ER stress and immune modulation of tumour cells
CDK4/6 inhibition and dsRNA sensor agonism co-operate to enhance anti-cancer effects through ER stress and immune modulation of tumour cells Open
Cytoplasmic pattern recognition receptors (PRRs) for double-stranded RNA (RIG-I/MDA5) are key mediators of anti-viral responses. PRR agonists, such as dsRNA oncolytic Reovirus type 3 Dearing (Rt3D), potently activate RNA sensors. We used a…
View article: Single-cell level temporal profiling of tumour-reactive T cells under immune checkpoint blockade
Single-cell level temporal profiling of tumour-reactive T cells under immune checkpoint blockade Open
The blockade of the immune checkpoints PD-1 and CTLA-4 enhances T cell response. However, it is largely unknown how antigen-reactive T cells regulate their checkpoint expression in vivo and whether and how the checkpoint blockade can chang…
View article: CD4 T cell dynamics shape the immune response to combination oncolytic herpes virus and BRAF inhibitor therapy for melanoma
CD4 T cell dynamics shape the immune response to combination oncolytic herpes virus and BRAF inhibitor therapy for melanoma Open
Background Combination herpes simplex virus (HSV) oncolytic virotherapy and BRAF inhibitors (BRAFi) represent promising immunogenic treatments for BRAF mutant melanoma, but an improved understanding of the immunobiology of combinations is …
View article: SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells
SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells Open
SOX11 is an embryonic mammary epithelial marker that is normally silenced prior to birth. High SOX11 levels in breast tumours are significantly associated with distant metastasis and poor outcome in breast cancer patients. Here, we show th…
View article: Author response: SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells
Author response: SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract SOX11 is an embryonic mammary epithelial m…
View article: Combining BRAF inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of BRAF-mutant thyroid cancer
Combining BRAF inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of BRAF-mutant thyroid cancer Open
Background The aggressive clinical behavior of poorly differentiated and anaplastic thyroid cancers (PDTC and ATC) has proven challenging to treat, and survival beyond a few months from diagnosis is rare. Although 30%–60% of these tumors c…
View article: Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases
Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases Open
The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of inducing angiogenesis, some cancers vascularize by the non-angiogenic mechanism of vessel co-option. Here…
View article: Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models
Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models Open
Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Important…