From Resistance to Sensitivity: Insights and Implications of Biphasic Modulation of Autophagy by Sunitinib
Abdel-Aziz, Amal Kamal; Abdel-Naim, Ashraf B; Shouman, Samia; Minucci, Saverio; Elgendy, Mohamed;
Abstract
Sunitinib, a multityrosine kinase inhibitor, is currently the standard first-line therapy in metastatic renal cell carcinoma (mRCC) and is also used in treating patients with pancreatic neuroendocrine and imatinib-resistant gastrointestinal stromal tumors (GIST). Nevertheless, most patients eventually relapse secondary to intrinsic or acquired sunitinib resistance. Autophagy has been reported to contribute to both chemo-sensitivity and -resistance. However, over the last few years, controversial regulatory effects of sunitinib on autophagy have been reported. Since gaining insights into the underlying molecular insights and clinical implications is indispensible for achieving optimum therapeutic response, this minireview article sheds light on the role of a network of prosurvival signaling pathways recently identified as key mediators of sunitinib resistance with established and emerging functions as autophagy regulators. Furthermore, we underscore putative prognostic biomarkers of sunitinib responsiveness that could guide clinicians toward patient stratification and more individualized therapy. Importantly, innovative therapeutic strategies/approaches to overcome sunitinib resistance both evaluated in preclinical studies and perspective clinical trials are discussed which could ultimately be translated to better clinical outcome.
Other data
Title | From Resistance to Sensitivity: Insights and Implications of Biphasic Modulation of Autophagy by Sunitinib | Authors | Abdel-Aziz, Amal Kamal ; Abdel-Naim, Ashraf B; Shouman, Samia; Minucci, Saverio; Elgendy, Mohamed | Keywords | Mcl-1; Sunitinib; autophagy; cancer; mTOR; resistance | Issue Date | 2017 | Publisher | FRONTIERS MEDIA SA | Journal | Frontiers in pharmacology | ISSN | 1663-9812 | DOI | 10.3389/fphar.2017.00718 | PubMed ID | 29066973 | Scopus ID | 2-s2.0-85030983208 | Web of science ID | WOS:000412576300001 |
Attached Files
File | Description | Size | Format | Existing users please Login |
---|---|---|---|---|
FromResistance.pdf | 756.46 kB | Adobe PDF | Request a copy |
Similar Items from Core Recommender Database
Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.