misunderstanding about drug discovery# Biology - 生物学
P*e
1 楼
After reading the comments about NIH, it seems to me people here has a
misunderstanding about the drug discovery process. People seem to believe
the drug discovery has always progressed like this: target---pathway---
cellular model---animal model---human beings. Indeed this is the well
publicized model or paradigm. But years ago, people used a phenotypic
screening to search for drugs without knowing targets, often directly on
animals. For anti-cancer drugs, many old ones were discovered without
knowing the MOA, including taxol. But with the advent of oncogenes, a more
reductionist approach as we all see today emerged. This approach indeed
discovered important anticancer drugs including the poster child of this
approach: gleevec. But we should remember CML is a simple and well defined
cancer in terms of genetic mutation. Bcr-abl mutation accounts for about 95%
of the cases, making it a perfect target. But for complex cancers such as
pancreatic cancer, there are many mutations (65?), the targeted approach
obviously is not working. That is why people in the drug discovery community
are advocating to going back to the traditional phenotypic screening at
least for complex diseases like cancer and other aging-related diseases.
misunderstanding about the drug discovery process. People seem to believe
the drug discovery has always progressed like this: target---pathway---
cellular model---animal model---human beings. Indeed this is the well
publicized model or paradigm. But years ago, people used a phenotypic
screening to search for drugs without knowing targets, often directly on
animals. For anti-cancer drugs, many old ones were discovered without
knowing the MOA, including taxol. But with the advent of oncogenes, a more
reductionist approach as we all see today emerged. This approach indeed
discovered important anticancer drugs including the poster child of this
approach: gleevec. But we should remember CML is a simple and well defined
cancer in terms of genetic mutation. Bcr-abl mutation accounts for about 95%
of the cases, making it a perfect target. But for complex cancers such as
pancreatic cancer, there are many mutations (65?), the targeted approach
obviously is not working. That is why people in the drug discovery community
are advocating to going back to the traditional phenotypic screening at
least for complex diseases like cancer and other aging-related diseases.
