Combination strategies to overcome drug resistance in metastatic colorectal cancer
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AbstractDescription: Colorectal cancer is a leading cause of cancer-related death worldwide. In recent years, monoclonal antibodies targeting EGFR (cetuximab and panitumumab) or VEGFR (bevacizumab) have achieved improved disease control in patients with chemo-refractory mCRC. However, only a small percentage of mCRC patients are sensitive to these targeted therapies and they will eventually become refractory to the treatment. Human antigen R (HuR) is a RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. Many of the HuR target mRNAs encode proteins important for tumorigenesis, angiogenesis, and tumor metastasis. HuR overexpression is known to correlate with high-grade malignancy and poor prognosis in CRC. Novel small molecule HuR inhibitors have been identified by high throughput screening with promising anticancer activity. We discuss the potential circumvention of resistance to EGFR/VEGFR targeted therapy by HuR inhibitors via the inhibition of bypass and compensatory membrane growth factors, including VEGF, IGF and ERBB2.
Acceptance Date04/11/2018
All Author(s) ListWU Mingxia Mia, TO Kin-Wah Kenneth
Name of ConferenceAmerican Association of Pharmaceutical Scientists Annual Meeting 2018
Start Date of Conference04/11/2018
End Date of Conference07/11/2018
Place of ConferenceWashington D.C., USA
Country/Region of ConferenceUnited States of America
LanguagesEnglish-United States

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