Sacco Paola Claudia, Gridelli Cesare
a Division of Medical Oncology , 'S.G. Moscati' Hospital , Avellino , Italy.
Expert Opin Emerg Drugs. 2017 Sep;22(3):213-222. doi: 10.1080/14728214.2017.1369952.
Mitosis is necessary to sustain life and is followed immediately by cell division into two daughter cells. Microtubules play a key role in the formation of the mitotic spindle apparatus and cytokinesis at the end of mitosis. Various anti-microtubule agents such as taxanes and vinca alkaloids are widely used in the treatment of advanced non-small cell lung cancer (NSCLC) but their use is associated with hematologic toxicity profile, acquired resistance and hypersensitivity reactions. Areas covered: The Nab-paclitaxels are the more recent antimitotic agents approved in NSCLC showing a better tolerability and activity when compared to previous ones. Despite this, the outcome of patients with advanced non-small cell lung cancer is poor. Due to the key role of mitosis, research is focused on the identification of new mitotic drug targets other than microtubule inhibitors, such as cell cycle targets, aurora kinases and Polo-like kinases. Expert opinion: Despite improvements in chemotherapeutic choices and supportive care, the majority of patients experience a deteriorating quality of life and significant toxicities associated to a poor outcome. Thus, the therapeutic management of patients with advanced NSCLC represents an ongoing challenge and novel agents targeting mitosis are under investigation.
有丝分裂对于维持生命是必要的,并且紧接着会发生细胞分裂形成两个子细胞。微管在有丝分裂纺锤体装置的形成以及有丝分裂末期的胞质分裂过程中起着关键作用。各种抗微管药物,如紫杉烷类和长春花生物碱,被广泛用于治疗晚期非小细胞肺癌(NSCLC),但其使用与血液学毒性特征、获得性耐药和超敏反应相关。涵盖领域:纳米白蛋白结合型紫杉醇是最近在NSCLC中获批的抗有丝分裂药物,与之前的药物相比,显示出更好的耐受性和活性。尽管如此,晚期非小细胞肺癌患者的预后仍然很差。由于有丝分裂的关键作用,研究集中在识别除微管抑制剂之外的新的有丝分裂药物靶点,如细胞周期靶点、极光激酶和波罗样激酶。专家观点:尽管化疗选择和支持治疗有所改善,但大多数患者的生活质量仍在恶化,且与不良预后相关的毒性反应严重。因此,晚期NSCLC患者的治疗管理仍然是一项持续的挑战,针对有丝分裂的新型药物正在研究中。