在化疗中结直肠肝转移的遗传和微环境演变
Min Shi1, Yingxi Yang2, Na Huang3
1Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; Cancer Center, the Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China; Foshan Key Laboratory of Translational Medicine in Oncology, the Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China.
Cell reports. Medicine
|December 4, 2024
概括
结直肠癌肝转移 (CRLM) 中的耐药性主要在转录层面发展,而不是基因组层面. STAT3信号抑制克服了SMAD4突变细胞中的抵抗.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 药物耐药性限制了结直肠癌肝转移 (CRLM) 中的化疗疗效率.
- 了解治疗期间CRLM的演变对于改善结果至关重要.
研究的目的:
- 为了阐明CRLM在基于贝瓦齐祖马布 (BVZ) 的化疗期间的进化动态.
- 确定CRLM内在和获得药物耐药性的机制.
- 发现克服治疗耐药性的策略.
主要方法:
- 对来自49名接受基于BVZ的化疗的患者的115个CRLM样本进行了多个OMIC分析.
- 解离内在和获得的阻力机制.
- 基因干扰实验和体外药物敏感性测试.
主要成果:
- 基因组变化显示微小的变化 (92%的一致性),而转录基因组资料有显著差异.
- 肝细胞和骨髓细胞的透是获得耐药性的关键因素 (分别为38.5%和23.1%).
- SMAD4突变和chr20q副本数量的增加与内在化学抵抗有关.
- 通过STAT3信号传递,SMAD4突变会产生抗性,这种抗性可以通过STAT3抑制剂 (GB201) 逆转.
结论:
- 黄的耐药性主要是转录的,由微环境透和特定的遗传变化驱动.
- 将STAT3信号与化疗结合的向提供了一种有希望的策略,以克服SMAD4突变的CRLM中的耐药性.
相关概念视频
Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Adaptive Mechanisms in Cancer Cells
5.7K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K
Tumor Progression
6.2K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K
The Tumor Microenvironment
6.5K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.5K


