相关实验视频

Updated: Jun 10, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

在甲状腺癌中具有克隆性血液形成的向性治疗耐药性

Vera Tiedje, Pablo Sánchez Vela, Julie L Yang

bioRxiv : the preprint server for biology

|October 17, 2024

概括

在巨细胞中具有TET2突变的克隆性造血促进了类甲状腺癌 (ATC) 的生长和BRAF/MEK抑制剂耐药性. 向TGFβ信号可能会克服这种抗性,改善ATC和并发性CH患者的治疗结果.

科学领域:

在瘤学瘤学.
癌症生物学癌症生物学
血液学血液学血液学

背景情况:

无塑性甲状腺癌 (ATC) 具有侵略性,预后不佳,尽管对BRAF V600E突变进行了BRAF/MEK抑制.
ATC具有显著的髓状细胞透特征,特别是巨细胞,并且在患有TET2-突变克隆性血液形成 (CH) 的老年人群中很常见.
在固体瘤中CH-突变克隆的作用,包括它们对预后和治疗反应的影响,在很大程度上是未知的.

研究的目的:

调查TET2-突变性克隆造血 (CH) 在瘤微环境中的TET2-突变性克隆造血 (CH) 在形甲状腺癌 (ATC) 的作用.
确定CH突变巨细胞是否有助于ATC进展和抵抗BRAF/MEK抑制.
探索结合MAPK通路抑制与TGFβ信号封锁的治疗策略.

主要方法:

在固体瘤微环境中对TET2-突变CH丰富的分析和ATC患者的预后.
在小鼠Braf V600E突变ATC模型中透Tet2-突变巨细胞.
评估突变巨细胞对TGFβ家族连体过度表达及其在BRAF/MEK抑制剂耐药性中的作用.
对TGFβ信号抑制在恢复对MAPK通路抑制剂敏感性的评估.

主要成果:

TET2突变CH在固体瘤微环境中富含,并且与ATC患者的预后恶化有关.
泰特2突变巨细胞选择性地透到小鼠中的Braf V600E突变ATC中.
这些巨细胞对TGFβ家族配体的过度表达介导了对BRAF/MEK抑制的抗性.
在临床前模型中,抑制TGFβ信号恢复了对MAPK通路抑制剂的敏感性.

结论:

巨细胞中的TET2突变CH代表了对BRAF/MEK抑制剂在厌塑性甲状腺癌中耐药性的机制.
针对TGFβ信号提供了一个潜在的协同策略,以改善同时患有CH的ATC患者的治疗结果.
这项研究强调了在瘤微环境中考虑克隆性血液形成对于癌症治疗的重要性.

更多相关视频

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

Published on: April 17, 2013

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Treatment Resistant Cancers

Treatment Resistant Cancers

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...

Combination Therapies and Personalized Medicine

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...