Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Adv Exp Med Biol. 2019;1164:199-206. doi: 10.1007/978-3-030-22254-3_15.
Cancer cell heterogeneity is a universal feature of human tumors and represents a significant barrier to the efficacy and duration of anticancer therapies, especially targeted therapeutics. Among the heterogeneous cancer cell populations is a subpopulation of relatively quiescent cancer cells, which are in the G0/G1 cell-cycle phase and refractory to anti-mitotic drugs that target proliferative cells. These slow-cycling cells (SCCs) preexist in untreated tumors and frequently become enriched in treatment-failed tumors, raising the possibility that these cells may mediate therapy resistance and tumor relapse. Here we review several general concepts on tumor cell heterogeneity, quiescence, and tumor dormancy. We discuss the potential relationship between SCCs and cancer stem cells (CSCs). We also present our current understanding of how SCCs and cancer dormancy might be regulated. Increasing knowledge of SCCs and tumor dormancy should lead to identification of novel molecular regulators and therapeutic targets of tumor relapse, residual diseases, and metastasis.
肿瘤细胞异质性是人类肿瘤的普遍特征,也是抗癌疗法(尤其是靶向治疗)疗效和持续时间的重大障碍。在异质性肿瘤细胞群体中,存在一小部分相对静止的肿瘤细胞,它们处于 G0/G1 细胞周期阶段,对针对增殖细胞的抗有丝分裂药物具有抗性。这些缓慢循环的细胞(SCCs)预先存在于未经治疗的肿瘤中,并且在治疗失败的肿瘤中经常富集,这增加了这些细胞可能介导治疗抵抗和肿瘤复发的可能性。在这里,我们回顾了几个关于肿瘤细胞异质性、静止和肿瘤休眠的一般概念。我们讨论了 SCCs 与癌症干细胞(CSCs)之间的潜在关系。我们还介绍了我们目前对 SCCs 和癌症休眠如何受到调节的理解。对 SCCs 和肿瘤休眠的认识不断提高,应能确定肿瘤复发、残留疾病和转移的新的分子调节剂和治疗靶点。