Sobhani Navid, Corona Silvia P, Zanconati Fabrizio, Generali Daniele
Department of Medical, Surgery & Health Sciences, University of Trieste, Trieste, Italy.
Department of Radiation Oncology, Peter MacCallum Cancer Center, Moorabbin Campus, Australia.
Genes Cancer. 2017 Mar;8(3-4):495-496. doi: 10.18632/genesandcancer.138.
Malignant Mesothelioma (MM) is a rare and aggressive form of tumour that affects the lining of the internal organs for which current treatments have not been proven to be very effective. P16 tumour suppressor encoding CDKN2A gene is often downregulated in MM. This protein is a cyclin dependent kinase 4 and 6 inhibitor, that normally phosphorylates RB1, which has to be un-phosphorylated in order to block cell-cycle at G1 in normal cells. Adding CDK inhibitor molecules to MM in pre-clinical studies has been proven to restore the normal function of p16, blocking thereby MM cell cycle at G1. Future randomised phase III studies with CDK4/6 inhibitors in MM carrying relevant CDK4/6, cyclin D1/3 or p16 aberrations will be warranted.
恶性间皮瘤（MM）是一种罕见且侵袭性强的肿瘤形式，会影响内部器官的内膜，目前的治疗方法尚未被证明非常有效。编码CDKN2A基因的P16肿瘤抑制因子在MM中常常下调。这种蛋白质是一种细胞周期蛋白依赖性激酶4和6抑制剂，通常会磷酸化RB1，而在正常细胞中，RB1必须去磷酸化才能在G1期阻断细胞周期。在临床前研究中，向MM中添加CDK抑制剂分子已被证明可恢复p16的正常功能，从而在G1期阻断MM细胞周期。未来有必要对携带相关CDK4/6、细胞周期蛋白D1/3或p16畸变的MM患者进行CDK4/6抑制剂的随机III期研究。
