文章：

多重替代性有丝分裂信号通路的诱导伴随药物耐受性癌细胞的产生

Induction of Multiple Alternative Mitogenic Signaling Pathways Accompanies the Emergence of Drug-Tolerant Cancer Cells

原文发布日期：29 February 2024

DOI: 10.3390/cancers16051001

类型: Article

开放获取: 是

英文摘要：

Drug resistance can evolve from a subpopulation of cancer cells that initially survive drug treatment and then gradually form a pool of drug-tolerant cells. Several studies have pinpointed the activation of a specific bypass pathway that appears to provide the critical therapeutic target for preventing drug tolerance. Here, we take a systems-biology approach, using proteomics and genomics to examine the development of drug tolerance to EGFR inhibitors in EGFR-mutant lung adenocarcinoma cells and BRAF inhibitors in BRAF-mutant melanoma cells. We found that there are numerous alternative mitogenic pathways that become activated in both cases, including YAP, STAT3, IGFR1, and phospholipase C (PLC)/protein kinase C (PKC) pathways. Our results suggest that an effective therapeutic strategy to prevent drug tolerance will need to take multiple alternative mitogenic pathways into account rather than focusing on one specific pathway.

摘要翻译： 

耐药性可能源于最初在药物治疗中存活下来的癌细胞亚群，这些细胞随后逐渐形成药物耐受细胞池。多项研究已明确指出，特定旁路途径的激活似乎为预防药物耐受提供了关键的治疗靶点。本研究采用系统生物学方法，结合蛋白质组学与基因组学技术，探究EGFR突变型肺腺癌细胞对EGFR抑制剂及BRAF突变型黑色素瘤细胞对BRAF抑制剂产生药物耐受的发展过程。研究发现，在上述两种情况下均有大量替代性促有丝分裂通路被激活，包括YAP、STAT3、IGFR1以及磷脂酶C（PLC）/蛋白激酶C（PKC）通路。我们的结果表明，要制定有效预防药物耐受的治疗策略，需综合考虑多种替代性促有丝分裂通路，而非仅聚焦于单一特定通路。

原文链接：

Induction of Multiple Alternative Mitogenic Signaling Pathways Accompanies the Emergence of Drug-Tolerant Cancer Cells