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RAC1P29S Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance.
(2019-07)
RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study the role of RAC1P29S in melanoma development and reveal that RAC1P29S activates PAK, AKT, and a ...
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 ...
Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer.
(2019-09)
KRAS represents an excellent therapeutic target in lung cancer, the most commonly mutated form of which can now be blocked using KRAS-G12C mutant-specific inhibitory trial drugs. Lung adenocarcinoma cells harboring KRAS ...
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 ...
HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation.
(BIOMED CENTRAL LTD, 2017-01-31)
BACKGROUND: Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced ...
Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei.
(AMER ASSOC CANCER RESEARCH, 2017-01-01)
AZD6738 is an orally active ATR inhibitor (ATRi) currently in phase I clinical trials. We found in vitro growth inhibitory activity of this ATRi in a panel of human cancer cell lines. We demonstrated radiosensitization by ...
CHK1 Inhibition Radiosensitizes Head and Neck Cancers to Paclitaxel-Based Chemoradiotherapy.
(AMER ASSOC CANCER RESEARCH, 2016-09-01)
Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths, with increasingly more cases arising due to high-risk human papillomavirus (HPV) infection. Cisplatin-based chemoradiotherapy is a ...
PARK2 Depletion Connects Energy and Oxidative Stress to PI3K/Akt Activation via PTEN S-Nitrosylation.
(CELL PRESS, 2017-03-16)
PARK2 is a gene implicated in disease states with opposing responses in cell fate determination, yet its contribution in pro-survival signaling is largely unknown. Here we show that PARK2 is altered in over a third of all ...
Single-Cell Dynamics Determines Response to CDK4/6 Inhibition in Triple-Negative Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2017-09-15)
Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer that is associated with a poor prognosis. We evaluated the activity of CDK4/6 inhibitors across the TNBC subtypes and investigated ...