The two faces of FBW7 in cancer drug resistance |
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Authors: | Wang Zhiwei Fukushima Hidefumi Gao Daming Inuzuka Hiroyuki Wan Lixin Lau Alan W Liu Pengda Wei Wenyi |
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Affiliation: | Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. |
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Abstract: | Chemotherapy is an important therapeutic approach for cancer treatment. However, drug resistance is an obstacle that often impairs the successful use of chemotherapies. Therefore, overcoming drug resistance would lead to better therapeutic outcomes for cancer patients. Recently, studies by our own and other groups have demonstrated that there is an intimate correlation between the loss of the F-box and WD repeat domain-containing 7 (FBW7) tumor suppressor and the incurring drug resistance. While loss of FBW7 sensitizes cancer cells to certain drugs, FBW7-/- cells are more resistant to other types of chemotherapies. FBW7 exerts its tumor suppressor function by promoting the degradation of various oncoproteins that regulate many cellular processes, including cell cycle progression, cellular metabolism, differentiation, and apoptosis. Since loss of the FBW7 tumor suppressor is linked to drug resistance, FBW7 may represent a novel therapeutic target to increase drug sensitivity of cancer cells to conventional chemotherapeutics. This paper thus focuses on the new functional aspects of FBW7 in drug resistance. |
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Keywords: | cancer drug resistance FBW7 Mcl‐1 p53 tumor suppressor |
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