癌症研究术语 | vulnerability | Dependency | viability | synthetic lethality | sensitivity | resistance | Fitness

 

2023年01月28日

Moreover, genomics often cannot distinguish “passenger” mutations from “drivers” that promote tumorigenesis and might be therapeutic targets.

什么是driver，什么是passenger？

Drivers are defined as mutations that confer a fitness advantage to somatic cells in their microenvironment, thereby driving the cell lineage to cancer (2,). Conversely, passengers (also termed “hitchhikers”) are defined as mutations that provide no such proliferative benefit (2,).

Mutations that provide a selective growth advantage, and thus promote cancer development, are termed driver mutations, and those that do not are termed passenger mutations (4). The terms driver and passenger may also be used to refer to the genes harboring driver mutations. Genes that have been identified as drivers in at least one cancer type are described as cancer genes (5).

 

It is now well accepted that virtually all cancers result from the accumulated mutations in genes that increase the fitness of a tumor cell over that of the cells that surround it (1, 2). “Fitness” is defined as the net replication rate, i.e., the difference between the rate of cell birth and cell death.

 

 

什么是cancer vulnerability？缺点，缺陷。

什么是Cancer Dependency？依赖，A cancer genetic dependency can be broadly defined as a gene that is required for cancer cell proliferation and/or survival. 通俗理解就是癌症细胞赖以生存的一切，没有它，癌症就无法维持。

什么是viability？生存，跟survive、growth是类似的。

什么是susceptibility？易感性，容易理解，比如你带了某个突变，某些疾病风险就更大。

什么是synthetic lethality？就是两个基因任何一个单独不致死，两个基因都突变才致死，已有成功药物。

什么是drug sensitivity？敏感性与drug浓度有关，是个人的属性，指个人是否对某个drug有sensitivity，有时候药物初期是有用的，后期就无用了，所以就以这个来形容有效的剂量和浓度。

什么是drug resistance？到治疗后期，肿瘤已经进化，产生了耐药性，也就是不再有sensitivity。

Fitness？ net replication rate, i.e., the difference between the rate of cell birth and cell death.

 

Cancer cells often have mutations in anticancer genes that make their survival dependent on other genes.

The gene-editing approach CRISPR–Cas9 offers a way to identify such vulnerabilities.

certain tumours that have deficiencies in a type of DNA-repair process require an enzyme called Werner syndrome ATP-dependent helicase (WRN) for their survival.

If inhibitors of WRN are found, such molecules might be promising drug candidates for further testing.

 

However, loss-of-function mutations can render cancer cells dependent on specific genes through a principle known as synthetic lethality

These and other successes have inspired many efforts to search for synthetically lethal genetic relationships involving commonly mutated tumour-suppressor genes such as TP53, PTEN and RB1.

 

 

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posted @ 2022-12-29 02:44  Life·Intelligence  阅读(280)  评论(0)  编辑  收藏  举报
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