美国加州大学戴维斯分校一个研究小组最近发现了一种可以阻断肾癌细胞自我修复的新方法，这一成果有望使肾癌化疗更为有效，也更易承受。
癌细胞最典型的特点就是能够快速复制，而肾癌是最难治疗的癌症之一，因为它在扩散到其他器官之前通常并无明显症状。目前的一些肾癌化疗方案可以减缓癌细胞复制，延长患者存活期，但药物毒性也会导致严重副作用。有关专家指出，如果能进一步提高肾癌化疗的有效性，就可以最大限度杀死癌细胞，减少化疗次数和用药量，从而减少患者痛苦。
研究小组在新一期《癌症生物学和疗法》杂志上介绍说，在包括肾癌在内的多种癌症中，p21基因都扮演了重要角色，它帮助修复癌细胞的脱氧核糖核酸（DNA），尤其在面对肾癌化疗药物攻击时，它可以帮助癌细胞自我修复，从而降低化疗有效性。科研人员试图找到能够阻断p21基因通路的“特效”化合物。
据研究负责人罗伯特·魏斯介绍，他们经过多次实验，终于发现3种很特别的化合物能够显著降低p21基因的表达，阻断肾癌细胞自我修复的过程，使化疗药物更加容易对癌细胞产生作用。
研究小组还将深入研究这3种化合物，以确定它们能发挥效用的最低浓度，并进一步优化它们的抗癌特性。之后，他们将把3种化合物与标准的肾癌化疗方案相结合，以探索出新的疗法。（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer Biology & Therapy，volume 7, issue 12, 2015 - 2022，See-Hyoung Park，Ruiwu Liu
High throughput screening of a small molecule one-bead-one-compound combinatorial library to identify attenuators of p21 as chemotherapy sensitizers
See-Hyoung Park, Xiaobing Wang, Ruiwu Liu, Kit S. Lam and Robert H Weiss
Kidney cancer is notoriously difficult to treat when metastatic due to its resistance to conventional chemotherapy. p21 is a cyclin kinase inhibitor which, in many tumor cell lines, conveys an anti-apoptotic function through its induction by the DNA damage responsive p53 pathway, such that attenuation of p21 sensitizes several disparate cancer cell lines to DNA-damaging chemotherapy. Since clinical applications with therapeutic antisense and siRNA approaches are problematic, we sought to discover other methods to inhibit p21 which are more readily translatable to the clinic. Utilizing an on-bead enzyme-linked colorimetric binding assay, we screened a diverse one-bead-one-compound combinatorial small molecule library, and identified 12 candidate compounds which bind p21. Each of the 12 candidate compounds was synthesized and tested individually, and 3 ligands were found which had the highest p21 binding affinity and yielded similar chemical structure. These 3 compounds caused dose-dependent cytotoxicity as well as apoptosis when exposed to two RCC cell lines. In addition, these compounds sensitized cells to apoptosis when incubated with doxorubicin such that a lower dose of doxorubicin was required in the presence of the compounds for equivalent cell killing. Interestingly, a representative of the 3 compounds decreased p21 levels by specific induction of ubiquitin-dependent proteosome degradation. Thus, by high throughput screening of thousands of candidate small molecules, we have identified compounds which attenuate p21, cause RCC cell apoptosis, and sensitize RCC cells to DNA-damaging chemotherapy. These compounds are currently being evaluated in in vivo assays as potential novel therapeutic for RCC.
