乳腺癌干细胞抵抗放射治疗及化疗的调控机制

Radiation resistance and chemoresistance of cancer stem cells in human breast cancer

据中国城市癌症报告统计,乳腺癌是中国城市女性发病率最高的癌症。尽管乳腺癌早期原位切除及放射治疗和化疗(简称放化疗)后,患者的5年和10年生存率较好,但依旧有小部分癌细胞逃逸、潜伏和扩散,导致乳腺癌复发和转移。未治愈乳腺癌中,约70%发生肺转移,60%发生骨转移和肝转移,15%发生脑转移。肿瘤干细胞是肿瘤组织中存在的少量具有干细胞特征的细胞亚群,有极强的再生肿瘤能力以及天然放化疗抵抗能力,被视作乳腺癌复发、转移的主要原因。靶向肿瘤干细胞的研究,为人类彻底攻克恶性肿瘤带来了希望。乳腺癌组织中具备乙醛脱氢酶(+)、CD44^+ CD24^-Lin^-等特征的细胞亚群已经被证实是乳腺肿瘤干细胞。笔者总结了乳腺肿瘤干细胞的鉴定、起源、特征、调控机制、放化疗不敏感的原因及临床靶向治疗的研究进展,供同行参考。

According to the statistic data of cancer in China, breast cancer has the highest incidence in female residents in cities of China. Although the traditional therapies, including surgery, radiation therapy, chemotherapy and hormone therapy have led to the increased 5-year and 10-year survival, there are still a small number of cancer cells survived from treatment, causing cancer recurrence and/or metastasis. Around 70% of survived breast cancer can metastasize to the lung, 60% to the bone and liver and 15% to the brain. Breast cancer stem cells, a subpopulation of breast cancer cells carrying stem cell properties, have strong ability to regenerate tumor and natural resistance to radiation and chemotherapy, which may be responsible for cancer recurrence and metastasis. The strategies targeting at cancer stem cell bring new hope for the treatment of cancer in the near future. In human breast cancer tissues, ALDH positive cells and CD44^+CD24^-Lin^- cells have been identified as breast cancer stem cells. In this review, we discussed the identification, origin, properties, regulatory mechanism of breast cancer stem cells and the resistance against radiation and chemotherapy, as well as the advances of clinical targeted therapy.