Peptide Research Laboratories, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Curr Drug Deliv. 2011 Jan;8(1):2-10. doi: 10.2174/156720111793663633.
Somatostatin receptors (SSTRs), especially SSTR subtype 2, are found expressed at relatively higher levels in many tumor cells and in tumoral blood vessels relative to normal tissues. This creates an opportunity for developing various cytotoxic SST conjugates that selectively target SSTR2-specific sites. Accordingly, some potent chemotherapeutic agents such as camptothecin (CPT), methotrexate (MTX), paclitaxel (PTX) and doxorubicin (DOX) have been coupled to SSTR2-preferential somatostatin (SST) analogs. These new cytotoxic SST conjugates display significant SSTR-selective anti-tumor abilities in many different types of tumors. For instance, the CPT-SST conjugate JF-10-81, in which CPT is coupled to the N-terminus of a SSTR2-specific SST analog (JF-07-69), had wide ranging anti-tumor and anti-angiogenic ability. This conjugate also showed an ability to overcome multi-drug resistance (MDR) in SSTR-over-expressing and CPT-insensitive human pancreatic carcinoid BON cells. Notably, another DOX-SST conjugate, AN-238, made by coupling pyrrolino-DOX to the SST analog RC-121, displayed indirect anti-tumor activity against SSTR-negative, non-small cell lung cancer H-157 tumor growth by directly targeting SSTR-positive tumoral vessels of host mice. These cytotoxic SST conjugates should deliver chemotherapeutic agents to receptor-specific sites, enhance anti-tumor efficacy, reduce toxic side effects to normal tissues, and to some extent, overcome MDR. These and other peptide conjugates may possibly represent a newer generation of receptor-targeted cancer therapeutics. This review discusses the progress with reference to SST-based and SSTR-selective cytotoxic cancer therapy.
生长抑素受体（SSTRs），特别是 SSTR 亚型 2，在许多肿瘤细胞和肿瘤血管中相对较高水平表达，而在正常组织中则表达较低。这为开发各种细胞毒性 SST 缀合物提供了机会，这些缀合物可以选择性地靶向 SSTR2 特异性位点。因此，一些有效的化疗药物，如喜树碱（CPT）、甲氨蝶呤（MTX）、紫杉醇（PTX）和多柔比星（DOX），已被连接到 SSTR2 优先的生长抑素（SST）类似物上。这些新的细胞毒性 SST 缀合物在许多不同类型的肿瘤中显示出显著的 SSTR 选择性抗肿瘤能力。例如，CPT-SST 缀合物 JF-10-81，其中 CPT 连接到 SSTR2 特异性 SST 类似物（JF-07-69）的 N 端，具有广泛的抗肿瘤和抗血管生成能力。该缀合物还显示出克服 SSTR 过度表达和 CPT 不敏感的人胰腺类癌 BON 细胞中多药耐药（MDR）的能力。值得注意的是，另一种 DOX-SST 缀合物 AN-238，是通过将吡咯啉-DOX 连接到 SST 类似物 RC-121 制成的，通过直接靶向宿主小鼠的 SSTR 阳性肿瘤血管，对 SSTR 阴性、非小细胞肺癌 H-157 肿瘤生长显示出间接的抗肿瘤活性。这些细胞毒性 SST 缀合物应将化疗药物递送到受体特异性部位，增强抗肿瘤疗效，减少对正常组织的毒性副作用，并在某种程度上克服 MDR。这些和其他肽缀合物可能代表新一代的受体靶向癌症治疗药物。本文综述了基于 SST 和 SSTR 选择性细胞毒性癌症治疗的进展。
