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ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment.
(AMER ASSOC CANCER RESEARCH, 2019-06-01)
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 ...
PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma.
(AMER ASSOC CANCER RESEARCH, 2019-06-01)
PURPOSE: The prevention and treatment of metastatic sarcoma are areas of significant unmet need. Immune checkpoint inhibitor monotherapy has shown little activity in sarcoma and there is great interest in identifying novel ...
ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma.
(NATURE PUBLISHING GROUP, 2019-05-09)
Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug ...
Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders.
(AMER CHEMICAL SOC, 2020-04-23)
Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). ...
Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation.
(AMER SOC CLINICAL INVESTIGATION INC, 2019-08-08)
Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are ...
Androgen receptor splice variant-7 expression emerges with castration resistance in prostate cancer.
(AMER SOC CLINICAL INVESTIGATION INC, 2019-01-02)
BACKGROUND: Liquid biopsies have demonstrated that the constitutively active androgen receptor splice variant-7 (AR-V7) associates with reduced response and overall survival from endocrine therapies in castration-resistant ...
Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo.
(SPRINGER, 2020-07-01)
PURPOSE: Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we examined poly(ADP-ribose) polymerase 1 (PARP1) ...
Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non-small Cell Lung Cancer.
(AMER ASSOC CANCER RESEARCH, 2019-07-01)
PURPOSE: Hypoxia is associated with poor prognosis and is predictive of poor response to cancer treatments, including radiotherapy. Developing noninvasive biomarkers that both detect hypoxia prior to treatment and track ...
A new method for the high-precision assessment of tumor changes in response to treatment.
(OXFORD UNIV PRESS, 2018-08-01)
MOTIVATION: Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both development and also in response to treatment. The ...
A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds.
(CELL PRESS, 2016-09-22)
The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the ...