Conor C. Lynch
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View article: PRDM16 Regulates Prostate Cancer Cell Dormancy and Prevents Bone Metastatic Outgrowth
PRDM16 Regulates Prostate Cancer Cell Dormancy and Prevents Bone Metastatic Outgrowth Open
Understanding dormancy in prostate cancer (PCa) is challenging due to model availability. Here, using murine and human PCa cell lines, we generated a stress-induced model of dormancy in vitro and demonstrated that the phenotype could be su…
View article: Unc-51 Like Kinase 3 (ULK3) is essential for autophagy and cell survival in multiple myeloma
Unc-51 Like Kinase 3 (ULK3) is essential for autophagy and cell survival in multiple myeloma Open
Despite the availability of effective therapies such as proteasome inhibitors, multiple myeloma (MM) patients relapse with refractory disease. To identify new therapeutic targets, we assessed RNA sequencing data from CD138+ MM patient cell…
View article: Epigenetic Plasticity Drives Carcinogenesis and Multi-Therapy Resistance in Multiple Myeloma
Epigenetic Plasticity Drives Carcinogenesis and Multi-Therapy Resistance in Multiple Myeloma Open
We demonstrate that carcinogenesis and multi-therapy resistance in multiple myeloma (MM)—a treatable yet incurable plasma cell malignancy—are driven by epigenetic dysregulation. In this new paradigm, genomic and cytogenetic events unlock e…
View article: Data from The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma
Data from The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma Open
Several therapeutic agents have been approved for treating multiple myeloma, a cancer of bone marrow–resident plasma cells. Predictive biomarkers for drug response could help guide clinical strategies to optimize outcomes. In this study, w…
View article: Supplementary Data from The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma
Supplementary Data from The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma Open
This file contains four supplementary tables S1 - S4 and eight supplementary figures S1 - S8.
View article: Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed / refractory multiple myeloma
Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed / refractory multiple myeloma Open
Multiple myeloma (MM) patients are often refractory to targeted therapies including proteasome inhibitors (PIs). Here, analysis of RNA sequencing data derived from 672 patients with newly diagnosed or relapsed/refractory disease identified…
View article: The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma
The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma Open
Several therapeutic agents have been approved for treating multiple myeloma, a cancer of bone marrow–resident plasma cells. Predictive biomarkers for drug response could help guide clinical strategies to optimize outcomes. In this study, w…
View article: Emerging roles for stromal cells in bone metastasis
Emerging roles for stromal cells in bone metastasis Open
The skeleton is a common site of cancer metastasis and malignancy with the resultant lesions often being incurable. Interactions between metastatic cancer cells and the bone microenvironment are critical for cancer cell survival, outgrowth…
View article: #1. Acid ceramidase (ASAH1) is a key mediator of drug resistance in relapsed/refractory multiple myeloma
#1. Acid ceramidase (ASAH1) is a key mediator of drug resistance in relapsed/refractory multiple myeloma Open
View article: The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease
The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease Open
Multiple myeloma (MM) is an osteolytic malignancy that is incurable due to the emergence of treatment resistant disease. Defining how, when and where myeloma cell intrinsic and extrinsic bone microenvironmental mechanisms cause relapse is …
View article: A broad scope, a broad readership, and a broad purpose
A broad scope, a broad readership, and a broad purpose Open
The long battle with cancer began centuries ago and despite many victories, the overall incidence continues to rise and it sometimes feels like that we are losing the war. The high rates and mortality of cancer have brought an increasing b…
View article: How circulating tumor cluster biology contributes to the metastatic cascade: from invasion to dissemination and dormancy
How circulating tumor cluster biology contributes to the metastatic cascade: from invasion to dissemination and dormancy Open
Circulating tumor cells (CTCs) are known to be prognostic for metastatic relapse and are detected in patients as solitary cells or cell clusters. Circulating tumor cell clusters (CTC clusters) have been observed clinically for decades and …
View article: γδ-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer
γδ-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer Open
Immune checkpoint blockade has been largely unsuccessful for the treatment of bone metastatic castrate-resistant prostate cancer (mCRPC). Here, we report a combinatorial strategy to treat mCRPC using γδ-enriched chimeric antigen receptor (…
View article: Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment
Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment Open
In human prostate to bone metastases and in a novel rodent model that recapitulates prostate tumor–induced osteolytic and osteogenic responses, we found that osteoclasts are a major source of the proteinase, matrix metalloproteinase (MMP)-…
View article: Data from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics
Data from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics Open
Synergistic action of kinase and BET bromodomain inhibitors in cell killing has been reported for a variety of cancers. Using the chemical scaffold of the JAK2 inhibitor TG101348, we developed and characterized single agents which potently…
View article: Supplementary Tables S1-S3 and Figures S1-S11 from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics
Supplementary Tables S1-S3 and Figures S1-S11 from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics Open
Table S1: Crystallographic data collection and refinement statistics Table S2: Inhibitory activity against other BET bromodomains Table S3: Bromodomain profiling data Fig. S1: Detailed binding interactions of compounds 1 - 5 in BRD4-1 Fig.…
View article: Supplementary Tables S4, S5 from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics
Supplementary Tables S4, S5 from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics Open
Table S4: Kinome profiling data (Microsoft Excel sheet) Table S5: Cell line screening data (Microsoft Excel sheet)
View article: Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment
Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment Open
In human prostate to bone metastases and in a novel rodent model that recapitulates prostate tumor–induced osteolytic and osteogenic responses, we found that osteoclasts are a major source of the proteinase, matrix metalloproteinase (MMP)-…
View article: Data from Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth
Data from Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth Open
Bone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor- or host-derived MMP-2 contributes to brea…
View article: Data from Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth
Data from Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth Open
Bone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor- or host-derived MMP-2 contributes to brea…
View article: Data from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics
Data from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics Open
Synergistic action of kinase and BET bromodomain inhibitors in cell killing has been reported for a variety of cancers. Using the chemical scaffold of the JAK2 inhibitor TG101348, we developed and characterized single agents which potently…
View article: Supplementary Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment
Supplementary Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment Open
Supplementary Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment
View article: Supplementary materials from Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth
Supplementary materials from Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth Open
Table S1. UV calibration line parameters for BMMPI quantification. Figure S1. MMP-2 expression in murine and human breast cancer cell lines and BMMPI structure. Figure S2. Selective MMP-2 inhibition by the BMMPIs ML104 and ML115. Figure S3…
View article: Supplementary materials from Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth
Supplementary materials from Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth Open
Table S1. UV calibration line parameters for BMMPI quantification. Figure S1. MMP-2 expression in murine and human breast cancer cell lines and BMMPI structure. Figure S2. Selective MMP-2 inhibition by the BMMPIs ML104 and ML115. Figure S3…
View article: Supplementary Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment
Supplementary Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment Open
Supplementary Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment
View article: Supplementary Tables S1-S3 and Figures S1-S11 from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics
Supplementary Tables S1-S3 and Figures S1-S11 from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics Open
Table S1: Crystallographic data collection and refinement statistics Table S2: Inhibitory activity against other BET bromodomains Table S3: Bromodomain profiling data Fig. S1: Detailed binding interactions of compounds 1 - 5 in BRD4-1 Fig.…
View article: Supplementary Tables S4, S5 from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics
Supplementary Tables S4, S5 from Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics Open
Table S4: Kinome profiling data (Microsoft Excel sheet) Table S5: Cell line screening data (Microsoft Excel sheet)
View article: Data from Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma–Induced Osteolysis and Reduces Overall Survival
Data from Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma–Induced Osteolysis and Reduces Overall Survival Open
Multiple myeloma promotes systemic skeletal bone disease that greatly contributes to patient morbidity. Resorption of type I collagen–rich bone matrix by activated osteoclasts results in the release of sequestered growth factors that can d…
View article: Supplementary Data from Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma–Induced Osteolysis and Reduces Overall Survival
Supplementary Data from Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma–Induced Osteolysis and Reduces Overall Survival Open
All Supplementary Figures and Legends
View article: Data from Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma–Induced Osteolysis and Reduces Overall Survival
Data from Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma–Induced Osteolysis and Reduces Overall Survival Open
Multiple myeloma promotes systemic skeletal bone disease that greatly contributes to patient morbidity. Resorption of type I collagen–rich bone matrix by activated osteoclasts results in the release of sequestered growth factors that can d…