Editorial [Hot topic: Receptor-Targeted Cancer Therapy (Guest Editor: Li-Chun Sun)]
Conventional radiotherapy and chemotherapy have been applied to treatments after surgery or advanced/metastatic cancers. However, the applications have been limited, partly due to non-specificity that results in toxic side effects and to the eventual multi-drug resistance (MDR) that results from prolonged treatments. Considerable interest has been placed on receptor-targeted cancer therapy following the development of monoclonal antibody (mAb) technology by Kohler and Milstein in 1975. Certain receptors, such as somatostatin (SST) receptors (SSTRs) and gastrin releasing peptide (GRP) receptors, are found aberrantly expressed in much higher concentrations in many cancer cells than they are in normal cells. Peptides and mAbs used as drugdelivery systems have been broadly applied in receptor-targeted tumor imaging and radiotherapy/chemotherapy. During recent years, receptor-targeted nanotechnology has been developed as well. Generally, receptor-targeted therapeutics could increase efficacy and specificity, decrease toxic side effects and MDR. A classical example of increasing therapeutic specificity is that the SSTR2-specific AN-238, a conjugate of an octapeptide SST analog and 2-pyrrolino-DOX, displays potent indirect antitumor activity against human SSTR-negative non-SCLC NCI-H157 xenografts by directly targeting SSTR-positive tumor blood vessels of the host mice. However, these approaches display their own advantages and disadvantages, although great progress has been made. Peptides have some extra advantages. For instance, they are easy to synthesize and optimize and can be quickly investigated for their therapeutic potential since many peptides are relatively small molecules with very few amino acids. Many of these peptides undergo rapid internalization, quick circulatory clearance and good tumor tissue-penetrating ability. But peptides have a short half-life and lack both selectivity and high affinity compared to mAbs. mAbs have limited tumor penetration due to their large size and antigen heterogeneity to cancer cells, but have the advantages of high affinity, specificity and stability. Furthermore, antibodies need much more time to be taken up by tumors. Fab fragments of antibodies are quickly taken up by tumors, but rapid and high renal accumulation with low tumor-uptake rates limits their applications. Nanoparticles can be easily taken up by cancer cells and also by normal cells. In this thematic issue, we collect eight papers from different fields including receptor-targeted applications of nanoparticles, peptides and antibodies. Our attempt is to show the most current progression in these fields.
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Document Type: Research Article
Publication date: January 1, 2011
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