Growth Factor Signaling and Resistance to Cancer Chemotherapy
Zunyan Dai, Ying Huang and Wolfgang Sadee
Affiliation: Program of Pharmacogenomics,Department of Pharmacology, College of Medicine and Public health, TheOhio State University, 5168 Graves Hall, 333 West 10th Avenue,Columbus, OH 43210, USA
Keywords: pharmacogenomics, growth factors, growth factor receptors, growth factor signaling, chemoresistance, mechanisms of chemoresistance, antibody inhibitors, small molecular-weight inhibitors
Multiple mechanisms contribute to chemoresistance, eventually leading to failure of cancer chemotherapy. Deregulated growth factor signaling pathways promote cell proliferation and render cancer cells resistant to apoptosis, a common mechanism of chemoresistance. Therefore, inhibitors of growth factor signaling, including antibodies and small molecules, are promising drug candidates for chemotherapy, either given alone or as adjuvants to overcome general drug resistance. While dramatic responses have been attained in some cases, innate or acquired resistance to these novel anticancer drugs is common and limits broad applicability. Treatment failure may arise from complexity of growth factor signaling, with numerous parallel pathways and diverse downstream events. This review discusses the use of pharmacogenomics, assessing multiple growth factor signaling pathways and complex chemoresistance mechanisms. Monitoring expression profiles and activating mutations in growth factor receptors holds promise for the design of individualized therapy with a combination of drugs.
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