小柯机器人

意大利米兰大学Marco Cosentino Lagomarsino、都灵大学Alberto Bardelli等研究人员合作揭示结直肠癌持久细胞的群体动态和突变率特征。相关论文于2022年7月11日在线发表在《自然—遗传学》杂志上。

研究人员开发了一个定量框架，通过结合实验特征和数学建模来研究持久细胞。研究人员发现，在结直肠癌中，一部分持久细胞缓慢复制。经临床批准的靶向治疗会诱导转向耐药的持久细胞，并使其突变率暂时增加7-50倍，从而增加持久细胞衍生的耐药细胞数量。这些发现表明，治疗可能影响癌细胞的持久性和突变性，并将抑制易出错的DNA聚合酶作为限制肿瘤复发的一种策略。

据介绍，令人信服的证据表明，癌症持久细胞是对靶向治疗长期疗效的一个主要限制。然而，癌症宿主细胞的表型和种群动态仍然不清楚。

附：英文原文

Title: A modified fluctuation-test framework characterizes the population dynamics and mutation rate of colorectal cancer persister cells

Author: Russo, Mariangela, Pompei, Simone, Sogari, Alberto, Corigliano, Mattia, Crisafulli, Giovanni, Puliafito, Alberto, Lamba, Simona, Erriquez, Jessica, Bertotti, Andrea, Gherardi, Marco, Di Nicolantonio, Federica, Bardelli, Alberto, Cosentino Lagomarsino, Marco

Issue&Volume: 2022-07-11

Abstract: Compelling evidence shows that cancer persister cells represent a major limit to the long-term efficacy of targeted therapies. However, the phenotype and population dynamics of cancer persister cells remain unclear. We developed a quantitative framework to study persisters by combining experimental characterization and mathematical modeling. We found that, in colorectal cancer, a fraction of persisters slowly replicates. Clinically approved targeted therapies induce a switch to drug-tolerant persisters and a temporary 7- to 50-fold increase of their mutation rate, thus increasing the number of persister-derived resistant cells. These findings reveal that treatment may influence persistence and mutability in cancer cells and pinpoint inhibition of error-prone DNA polymerases as a strategy to restrict tumor recurrence. A modified fluctuation test applied to colorectal cancer cells shows that EGFR/BRAF inhibitor-induced persisters slowly proliferate and have an increased mutation rate. Error-prone DNA polymerases are identified as potential targets to avoid tumor recurrence following treatment with these drugs.

DOI: 10.1038/s41588-022-01105-z

Source: https://www.nature.com/articles/s41588-022-01105-z

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex