在慢性淋巴细胞白血病 (CLL) 中布鲁顿的氨酸激酶 (BTK) 突变:临床观点
Stefano Molica1, David Allsup1,2
1Department of Hematology, Hull University Teaching Hospitals NHS Trust, Hull, UK.
概括
布鲁顿的氨酸激酶抑制剂 (BTKis) 正在彻底改变慢性淋巴细胞白血病 (CLL) 治疗. 通过突变测试和新疗法克服BTKi耐药性,是患者持续反应的关键.
科学领域:
- 在瘤学瘤学.
- 血液学 血液学 血液学
- 分子生物学分子生物学
背景情况:
- 布鲁顿的氨酸激酶抑制剂 (BTKis) 已经改变了慢性淋巴细胞白血病 (CLL) 的管理.
- 第一代BTK像ibrutinib一样显示出有效性,但耐药性,通常通过BTK C481S突变,限制了长期的结果.
- 第二代BTKis和非共价抑制剂提供了更好的特征,但面临着新兴的耐药性.
研究的目的:
- 审查在CLL中BTKi治疗的不断变化的格局.
- 突出BTKi耐药机制的挑战及其临床影响.
- 讨论未来克服耐药性和个性化CLL治疗的战略.
主要方法:
- 在CLL中BTKi疗效和耐药性的文献综述.
- 分析新出现的抗性突变及其影响.
- 讨论当前和未来的治疗方法.
主要成果:
- BTKis显著改善了CLL的结果.
- BTK C481S突变是对共价BTK类抗性的主要机制.
- 新的抗药性突变继续出现,挑战目前的治疗方法.
- 非共价BTKs为复发患者提供了一个选择,但对抗性没有免疫力.
结论:
- 了解BTKi耐药性对于有效的CLL管理至关重要.
- 常规突变测试将指导个性化治疗策略.
- 需要未来的治疗方法,包括降解剂和免疫疗法,以克服耐药性并实现CLL的持久反应.
相关概念视频
Targeted Cancer Therapies
7.8K
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...
There are several types of targeted therapies against...
7.8K
Combination Therapies and Personalized Medicine
5.1K
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...
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...
5.1K
The Retinoblastoma Gene
4.2K
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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.2K
Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Receptor Tyrosine Kinases
14.3K
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
14.3K
Non-LTR Retrotransposons
11.9K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.9K


