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Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA.
(2017-12-12)
The immunosuppressive protein PD-L1 is upregulated in many cancers and contributes to evasion of the host immune system. The relative importance of the tumor microenvironment and cancer cell-intrinsic signaling in the ...
Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization.
(2015-12-06)
During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. ...
Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.
(2017-01)
Germline aberrations in critical DNA-repair and DNA damage-response (DDR) genes cause cancer predisposition, whereas various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality ...
Combining DNA damaging therapeutics with immunotherapy: more haste, less speed.
(2018-02)
The idea that chemotherapy can be used in combination with immunotherapy may seem somewhat counterproductive, as it can theoretically eliminate the immune cells needed for antitumour immunity. However, much preclinical ...
Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development.
(2019-01)
Cellular models for siRNA and small molecule high-throughput screening have been widely used in the last decade to identify targets for drug discovery. As an example, we present a twofold readout approach based on cell ...
In Vivo Characterization of 4 68Ga-Labeled Multimeric RGD Peptides to Image αvβ3 Integrin Expression in 2 Human Tumor Xenograft Mouse Models.
(2018-08)
αvβ3 integrins play an important role in angiogenesis and cell migration in cancer and are highly expressed on the activated endothelial cells of newly formed blood vessels. Here, we compare the targeting characteristics ...
The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations.
(2018-01)
Immunotherapy has led to a paradigm shift in the treatment of some malignancies, providing long-term, durable responses for a subset of patients with advanced cancers. Increasingly, research has identified links between ...
SHOC2 phosphatase-dependent RAF dimerization mediates resistance to MEK inhibition in RAS-mutant cancers.
(2019-06-10)
Targeted inhibition of the ERK-MAPK pathway, upregulated in a majority of human cancers, has been hindered in the clinic by drug resistance and toxicity. The MRAS-SHOC2-PP1 (SHOC2 phosphatase) complex plays a key role in ...
Dual blockade of the PI3K/AKT/mTOR (AZD8055) and RAS/MEK/ERK (AZD6244) pathways synergistically inhibits rhabdomyosarcoma cell growth in vitro and in vivo.
(AMER ASSOC CANCER RESEARCH, 2013-08-05)
PURPOSE: To provide rationale for using phosphoinositide 3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathway inhibitors to treat rhabdomyosarcomas, a major cause of pediatric and adolescent cancer deaths. ...
Dichloroacetate induces autophagy in colorectal cancer cells and tumours.
(NATURE PUBLISHING GROUP, 2014-07-15)
BACKGROUND: Dichloroacetate (DCA) has been found to have antitumour properties. METHODS: We investigated the cellular and metabolic responses to DCA treatment and recovery in human colorectal (HT29, HCT116 WT and HCT116 ...