Porta Camillo, Paglino Chiara, Mutti Luciano
Medical Oncology and Laboratory of Pre-Clinical Oncology and Developmental Therapeutics, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy.
Biologics. 2008 Dec;2(4):601-9. doi: 10.2147/btt.s2383.
Ribonucleases are a superfamily of enzymes which operate at the crossroads of transcription and translation, catalyzing the degradation of RNA; they can be cytotoxic because the cleavage of RNA renders indecipherable its information. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models. The maximum tolerated dose emerging from phase I studies was 960 g/m(2), with renal toxicity as the main dose-limiting toxicity. A large phase II trial showed that ranpirnase has disease-modifying activity against malignant mesothelioma. Ranpirnase proved to be superior to doxorubicin in a phase III trial, while preliminary results of another large, phase III trial, suggest that the combination of ranpirnase and doxorubicin could be more effective than doxorubicin alone. In all the above studies, ranpirnase seems to act mainly as a cytostatic rather than a cytotoxic drug, stabilizing progressive disease and potentially prolonging patients' survival. Ranpirnase may thus find its niche in combination with doxorubicin for mesothelioma as a second-line therapy, where no standard of care presently exists.
核糖核酸酶是一类酶的超家族，作用于转录和翻译的交叉点，催化RNA降解；它们可能具有细胞毒性，因为RNA的裂解会使其信息无法解读。兰瑞肽酶是一种新型核糖核酸酶，优先降解tRNA，从而导致蛋白质合成受到抑制，并最终导致细胞生长停滞和细胞毒性。兰瑞肽酶在多种肿瘤模型的体外和体内实验中均显示出抗肿瘤活性。I期研究得出的最大耐受剂量为960μg/m²，主要剂量限制性毒性为肾毒性。一项大型II期试验表明，兰瑞肽酶对恶性间皮瘤具有疾病改善活性。在一项III期试验中，兰瑞肽酶被证明优于阿霉素，而另一项大型III期试验的初步结果表明，兰瑞肽酶与阿霉素联合使用可能比单独使用阿霉素更有效。在上述所有研究中，兰瑞肽酶似乎主要作为一种细胞生长抑制剂而非细胞毒性药物发挥作用，稳定疾病进展并可能延长患者生存期。因此，兰瑞肽酶可能作为二线治疗药物，与阿霉素联合用于治疗间皮瘤，目前尚无标准的治疗方案。
