Model of tumor dormancy/recurrence after short-term chemotherapy.
Model of tumor dormancy/recurrence after short-term chemotherapy.
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DOI：
10.1371/journal.pone.0098021
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bachelder RE
中科院分区：
文献类型：
--
作者：
Li S;Kennedy M;Payne S;Kennedy K;Seewaldt VL;Pizzo SV;Bachelder RE
虽然许多肿瘤在新辅助化疗后会消退，但在大多数癌症患者治疗后都会检测到残留的肿瘤细胞。这些残留的肿瘤细胞被认为在恢复生长之前保持休眠多年，导致肿瘤复发。考虑到复发性肿瘤最常导致患者死亡，因此迫切需要研究驱动肿瘤休眠/复发的信号通路。我们已经开发了肿瘤休眠/复发的体外模型。肿瘤细胞（乳腺或前列腺）短期暴露于临床相关剂量的化疗可富集休眠肿瘤细胞群。在去除化疗后几天，休眠的肿瘤细胞恢复增殖能力并建立集落，类似于肿瘤复发。来自“复发性”集落的肿瘤细胞表现出增加的化疗抗性，类似于癌症患者中复发性肿瘤的治疗抗性。先前使用长期化疗选择模型的研究确定了驱动肿瘤耐药性的获得性突变。相比之下，我们的短期化疗暴露模型富集了慢循环、休眠、化疗耐药的肿瘤细胞亚群，其可以在药物去除后恢复生长。研究通过短期化疗富集的休眠肿瘤细胞中的独特信号通路有望确定预防肿瘤复发的新治疗靶点。
Although many tumors regress in response to neoadjuvant chemotherapy, residual tumor cells are detected in most cancer patients post-treatment. These residual tumor cells are thought to remain dormant for years before resuming growth, resulting in tumor recurrence. Considering that recurrent tumors are most often responsible for patient mortality, there exists an urgent need to study signaling pathways that drive tumor dormancy/recurrence. We have developed an in vitro model of tumor dormancy/recurrence. Short-term exposure of tumor cells (breast or prostate) to chemotherapy at clinically relevant doses enriches for a dormant tumor cell population. Several days after removing chemotherapy, dormant tumor cells regain proliferative ability and establish colonies, resembling tumor recurrence. Tumor cells from “recurrent” colonies exhibit increased chemotherapy resistance, similar to the therapy resistance of recurrent tumors in cancer patients. Previous studies using long-term chemotherapy selection models identified acquired mutations that drive tumor resistance. In contrast, our short term chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that can resume growth after drug removal. Studying unique signaling pathways in dormant tumor cells enriched by short-term chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence.
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影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
影响因子：
3.8
作者：
Brunsvig, Paal Fr;Andersen, Anders;Olsen, Harald
通讯作者：
Olsen, Harald
DOI：
10.1152/ajpheart.01052.2008
发表时间：
2008-12-01
影响因子：
4.8
作者：
Liu, Jinbao;Zheng, Hanqiao;Wang, Xuejun
通讯作者：
Wang, Xuejun
药物补偿和治疗超出进展 - 耐药性的刺激性。
DOI：
10.1038/nrclinonc.2013.158
发表时间：
2013-10
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Kuczynski EA;Sargent DJ;Grothey A;Kerbel RS
通讯作者：
Kerbel RS
影响因子：
45.3
作者：
Weiss, RB;Woolf, SH;Norton, L
通讯作者：
Norton, L