Molecular mechanism of antitumor activity of taxanes in lung cancer (Review).
Lung cancer is the most common cause of cancer mortality in both male and female patients in the United States of America, as well as in the rest of the world. Over one million people are diagnosed with lung cancer every year worldwide. The taxane is one of the most powerful classes of novel antitumor agents and has become an integral part of several commonly used chemotherapy regimens in lung cancer management over the past few years. Although the ability of taxanes to disrupt microtubule dynamics is well documented, the molecular basis by which taxanes suppress cancer cell growth and induce apoptotic cell death is not clearly defined. In this review, we focus on the molecular mechanisms of the antitumor activity of taxanes (paclitaxel and docetaxel) in lung cancer, and discuss the interactions of taxanes with microtubules, the roles of cell cycle control and cell death induction in the anticancer action of taxanes, as well as the signal transduction pathways involved in the processes. In addition, we discuss the possible mechanisms of taxane resistance, because drug resistance to these anti-neoplastic agents affects therapy efficacy and is also a major obstacle in the clinic for the successful treatment of lung cancer. Understanding the molecular mechanisms underlying the antitumor effect of taxanes and the drug resistance to taxanes may lead to the design of biologically and pharmacologically targeted therapeutic strategies for taxane resistant tumors, and to the improvement of chemotherapy effect and cancer patient survival.
Zhao
Jinshun
J
The Mary Babb Randolph Cancer Center, and Department of Microbiology, Immunology and Cell Biology, West Virginia University Health Sciences Center, Morgantown, 26506, USA.
Kim
Jee Eun
JE
Reed
Eddie
E
Li
Qingdi Q
QQ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D002453:Cell Cycle; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction; D043823:Taxoids / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids