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Introduction
Ovarian cancer is the most severe gynecologic malignancy, causing 114,000 deaths a year globally. In the USA alone, an estimated 23,000 women are diagnosed with ovarian cancer each year and the 5-year survival rate is merely 30% (1). In the United States, ovarian cancer represents 3% of all the new cancer cases in women, and accounts for 5% of all the cancer deaths (2). The high mortality is partly due to the frequent resistance of ovarian cancer to chemotherapy regimens. Paclitaxel combined with platinum remains to be the first line chemotherapy for ovarian cancer. Paclitaxel is a small molecule cytotoxin targeting tubulin and has strong cytostatic and apoptotic effects. Unfortunately, while most patients initially respond to this combined chemotherapy, the majority of these (up to 75%) will eventually relapse within 18 months with many having drug resistant disease (3). Ovarian cancer cells develop drug resistance through different pathways depending on the drug used (4). Multiple mechanisms can mediate the development of paclitaxel resistance, including changes in: i) the regulation or repair of the primary target of the drug (DNA, microtubule); ii) drug retention (increased efflux or decreased uptake); iii) drug inactivation or sequestration; and iv) signaling pathways that affect cell cycle/apoptosis. Paclitaxel is known to be transported by the ATP-dependent efflux pump P-glycoprotein (multidrug resistance, MDR) and upregulation of MDR has been associated with clinical drug resistance to various agents (5,6).
There is an imperative need for the development of new treatment modalities to improve the management of ovarian cancer patients. Switch to alternative drugs with different therapeutic mechanisms is one strategy to overcome the resistance against the presently used drugs. However, limited success has been achieved with the use of second line chemotherapy following the recurrence of ovarian cancer or the resistance to the first line drugs (7). This failure is often caused by the activation of ‘generic’ resistance mechanism against multiple drugs sharing a specific feature. Rationalized design and targeted chemotherapy using modified drugs equipped with new features to avoid the resistance of cancer cells may potentially enhance the drug efficacy and reduce the toxicity of cancer therapies.
SST is a cyclic polypeptide hormone that is found in most human organs and tissues. SST has a broad range of cellular functions such...