L******e
发帖数: 679 | 1 将会是肿瘤治疗的下一个‘泡泡’吗？
最近好像很火：
1,借着next generation sequencer' 的东风，大家都在疯狂的寻找‘dirver
mutations'.
2,制药公司在大量的筛选'small molecule inhibitors',这些小分子可以抑制突变了的
kinase,从而阻断肿瘤细胞的生长。
3, 前段时间的plx-4032，BRAF v600E 的inhibitor,80%有这个基因突变的皮肤癌病人
有效。
但是，几乎毫无列外，大概一年后肿瘤细胞会产生第二个突变，获得耐药性。
小弟刚刚接触这个行业，有大拿能展望一下吗？
另外，搞基础研究的大虾能不能提供一些关于小分子诱导基因突变机制的文章或者综述
。不是那种简单的化学物质能把某个基团变成另外基团的解释。
因为耐药性的产生不是随机的：例如肺癌病人对erlotinib的耐药性，50% 的病人是在
EGFR上产生第二个突变T790M,这个突变改变了erlotinib对EGFR 的亲和力。这中间肯定
存在调控，使有目的性的突变。 | w******e
发帖数: 1187 | 2 r u sure the mutation is caused by small molecule? my understanding is that
cancer cells randomly mutate but only certain mutation confers the receptor
"immunity" to the small molecule drugs. these two are different.
【在 L******e 的大作中提到】
: 将会是肿瘤治疗的下一个‘泡泡’吗？
: 最近好像很火：
: 1,借着next generation sequencer' 的东风，大家都在疯狂的寻找‘dirver
: mutations'.
: 2,制药公司在大量的筛选'small molecule inhibitors',这些小分子可以抑制突变了的
: kinase,从而阻断肿瘤细胞的生长。
: 3, 前段时间的plx-4032，BRAF v600E 的inhibitor,80%有这个基因突变的皮肤癌病人
: 有效。
: 但是，几乎毫无列外，大概一年后肿瘤细胞会产生第二个突变，获得耐药性。
: 小弟刚刚接触这个行业，有大拿能展望一下吗？
| L******e
发帖数: 679 | 3 We still don't know whether the drug "caused" the second mutation or just "
selected" a small amount cancer cells that carrying the mutation already.
Did you read any publications providing evidence?
that
receptor
【在 w******e 的大作中提到】
: r u sure the mutation is caused by small molecule? my understanding is that
: cancer cells randomly mutate but only certain mutation confers the receptor
: "immunity" to the small molecule drugs. these two are different.
| w******e
发帖数: 1187 | 4 are you seriously suggesting that some small molecule just so happen to
interact
with a protein, AND induce mutation of the gene of that very protein? I'd
like
to know any paper about this theory for sure.
hehe, anyway, merry xmas.
【在 L******e 的大作中提到】
: We still don't know whether the drug "caused" the second mutation or just "
: selected" a small amount cancer cells that carrying the mutation already.
: Did you read any publications providing evidence?
:
:
: that
: receptor
| L******e
发帖数: 679 | 5 i personally think the drugs just 'selected' the mutation. But there is no
any evidence up to now. I just want to know if anybody know any publications
about that. Or anyone is working on that topic. I am so interested in
getting to know that.
Merry Christmas!
【在 w******e 的大作中提到】
: are you seriously suggesting that some small molecule just so happen to
: interact
: with a protein, AND induce mutation of the gene of that very protein? I'd
: like
: to know any paper about this theory for sure.
: hehe, anyway, merry xmas.
| h******y
发帖数: 1374 | 6 one possibility is that targeted drugs lead to a subpopulation of cells
which becomes resistant by acquiring new mutations, rewiring signaling
pathways, gaining addiction to other key molecules.
this is a very important field that warrants more investigation but the
underlying mechanisms could be quite complicate |
|
