Macrophages can be co-opted to contribute to neoplastic, neurologic, and inflammatory diseases. Colony stimulating factor 1 receptor (CSF1R)-dependent macrophages and other inflammatory cells can suppress the adaptive immune system in cancer and contribute to angiogenesis, tumor growth, and metastasis. CSF1R-expressing osteoclasts mediate bone degradation in osteolytic cancers and cancers that metastasize to bone. In the rare disease tenosynovial giant cell tumor (TGCT), aberrant CSF1 expression...
#2Wulin Jiang(UNC: University of North Carolina at Chapel Hill)H-Index: 4
Last. Shawn Hingtgen(UNC: University of North Carolina at Chapel Hill)H-Index: 20
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Converting human fibroblasts into personalized induced neural stem cells (hiNSCs) that actively seek out tumors and deliver cytotoxic agents is a promising approach for treating cancer. Herein, we provide the first evidence that intravenously-infused hiNSCs secreting cytotoxic agent home to and suppress the growth of non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). Migration of hiNSCs to NSCLC and TNBC in vitro was investigated using time-lapse motion analysis, which ...
Recent studies have revealed that targeting amino acid metabolic enzymes is a promising strategy in cancer therapy. Acute myeloid leukemia (AML) downregulates the expression of argininosuccinate synthase (ASS1), a recognized rate-limiting enzyme for arginine synthesis, and yet displays a critical dependence on extracellular arginine for survival and proliferation. This dependence on extracellular arginine, also known as arginine auxotrophy, suggests that arginine deprivation would be a treatment...
BRAF-targeted therapies including vemurafenib (Zelboraf®) induce dramatic cancer remission, however, drug resistance commonly emerges. The purpose was to characterize a naturally-occurring canine cancer model harboring complex features of human cancer, to complement experimental models to improve BRAF-targeted therapy. A phase I/II clinical trial of vemurafenib was performed in pet dogs with naturally-occurring invasive urothelial carcinoma (InvUC) harboring the canine homologue of human BRAFV60...
Last. Andrew Bakshi(Peter MacCallum Cancer Centre)H-Index: 16
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Monotherapy with poly (ADP-ribose) polymerase (PARP) inhibitors is effective for the subset of castrate-resistant prostate cancer (CRPC) with defects in homologous recombination (HR) DNA repair. New treatments are required for the remaining tumours, and an emerging strategy is to combine PARP inhibitors with other therapies that induce DNA damage. Here we tested whether PARP inhibitors are effective for HR-proficient CRPC, including AR-null tumours, when used in combination with CX-5461, a small...
Last. Kwangok P. Nickel(UW: University of Wisconsin-Madison)H-Index: 7
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M6620, a selective ATP-competitive inhibitor of the ATM and RAD3-related (ATR) kinase, is currently under investigation with radiation in patients with non-small cell lung cancer (NSCLC) brain metastases. We evaluated the DNA damage response (DDR) pathway profile of NSCLC and assessed the radiosensitizing effects of M6620 in a preclinical NSCLC brain metastasis model. Mutation analysis and transcriptome profiling of DDR genes and pathways was performed on NSCLC patient samples. NSCLC cell lines ...
#2Grace A. McCarthy(OHSU: Oregon Health & Science University)H-Index: 1
Last. Aditi Jain(Thomas Jefferson University)H-Index: 7
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Pancreatic Ductal Adenocarcinoma (PDAC) is a lethal aggressive cancer, in part due to elements of the microenvironment (hypoxia, hypoglycemia) that cause metabolic network alterations. The FDA approved anti-helminthic Pyrvinium Pamoate (PP) has been previously shown to cause PDAC cell death, although the mechanism has not been fully determined. We demonstrated that PP effectively inhibited PDAC cell viability with nanomolar IC50s (9-93nM) against a panel of PDAC, patient-derived, and murine orga...
Last. Hyekyung P Cho(St. Jude Children's Research Hospital)
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Pediatric sarcomas represent a heterogeneous group of malignancies that exhibit variable response to DNA damaging chemotherapy. Schlafen family member 11 protein (SLFN11) increases sensitivity to replicative stress and has been implicated as a potential biomarker to predict sensitivity to DNA damaging agents (DDA). SLFN11 expression was quantified in 220 children with solid tumors using immunohistochemistry. Sensitivity to the PARP inhibitor talazoparib (TAL) and the topoisomerase I inhibitor ir...
Trophoblast cell surface antigen 2 (TROP2) is highly expressed on various epithelial tumors and correlates with poor prognosis. We developed the novel TROP2-directed antibody-drug conjugate (ADC), Datopotamab deruxtecan (Dato-DXd, DS-1062a), with a potent DNA topoisomerase I inhibitor (DXd), and evaluated its antitumor activity and safety profiles in preclinical models. The pharmacological activity and mechanism of action of Dato-DXd were investigated in several human cancer cell lines and xenog...
Inhibitors of apoptosis proteins (IAPs) are intracellular proteins, with important roles in regulating cell death, inflammation, and immunity. Here, we examined the clinical and therapeutic relevance of IAPs in colorectal cancer. We found that elevated expression of cIAP1 and cIAP2 (but not XIAP) significantly correlated with poor prognosis in patients with microsatellite stable (MSS) stage III colorectal cancer treated with 5-fluorouracil (5FU)-based adjuvant chemotherapy, suggesting their invo...