维护了vorasidenib不响应者的IDH突变和甲基化类:报告了2例病例
Mehdi Touat1,2, Jacqueline Lehmann-Che3,4, Salah Eddine O Kacimi2
1Department of Neuro-oncology, La Pitié Salpêtrière-Charles Foix Hospital Group, AP-HP Sorbonne University, Paris, France.
Neuro-oncology practice
|March 9, 2026
概括
沃拉西迪尼布在两名质瘤患者中没有引起IDH野生类克隆选择. 在中止伏拉西登尼布后,标准治疗仍然有效,这表明IDH突变质瘤的敏感性持续存在.
科学领域:
- 神经瘤学神经瘤学
- 分子诊断学 分子诊断学
- 临床试验分析临床试验分析
背景情况:
- 在INDIGO试验中,沃拉西迪尼 (vorasidenib) 改善了2级IDH突变质瘤的无进展生存率.
- 一部分患者 (20-25%) 在第一年内表现出疾病进展,引发了对抗药机制的担忧.
- 潜在的耐药性可能涉及到IDH野生类克隆的选择,影响未来的治疗疗效.
研究的目的:
- 调查vorasidenib在IDH突变质瘤中为IDH野生型克隆进行选择的潜力.
- 评估在放弃伏拉西代尼布后标准治疗的疗效,在进展的患者中.
主要方法:
- 两名患有2级IDH突变质瘤的患者的病例报告,他们接受了术后的vorasidenib.
- 对复发瘤的分子分析以确认IDH突变状态,MGMT状态和甲基化类.
- 评估治疗后对常规疗法 (手术,化疗,辐射) 的治疗反应.
主要成果:
- 在这两种情况下,沃拉西迪尼布的使用都未能阻止残留疾病的瘤进展.
- 停药后,两位患者对常规治疗有反应,IDH突变保留.
- 一个患者的疾病在3年内保持稳定;另一个患者出现复发.
结论:
- 沃拉西迪尼布在IDH突变质瘤中似乎不会对IDH野生类型克隆进行选择.
- 瘤对标准疗法的敏感性即使在治疗vorasidenib后也保持不变.
- 这些发现表明,对沃拉西迪尼布的耐药性可能不是由IDH野生型克隆选择驱动的.
相关概念视频
Treatment Resistant Cancers
3.9K
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...
3.9K
Loss of Tumor Suppressor Gene Functions
6.2K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.2K
Cancer-Critical Genes II: Tumor Suppressor Genes
10.0K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.0K
In-vitro Mutagenesis
17.5K
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
17.5K
Tumor Progression
7.7K
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...
7.7K


