One data showed that up to 97 per cent of all cancer drugs entering clinical trials end up in a clinical trial. Analysis, the cause is nothing but serious side effects, or lack of practical efficacy. If there are a few drugs that will encounter such problems, it may be understandable. But such a high proportion is hard to explain. Recently, a team from the well-known Cold Spring Harbor Laboratory found a potential reason: many anticancer drugs may have been misdesigned at the source…
The discovery was originally made of an accident. The team’s scientists discovered a strange phenomenon while sifting through anti-cancer targets. In many previously published papers, other scholars have argued that a protein called MELK is essential for the growth of cancer cells. But after the CRISPR gene edited, cancer cells that lack melK seem to be alive…
“We’re very surprised that these cancer cells aren’t dead,” said study author Professor Jason Sheltzer. “
The study’s correspondent, Professor Jason Sheltzer. Cold Spring Harbor Laboratory
This is very interesting. Previous scientists have developed a drug called OTS167 to inhibit melK’s function. It has entered Phase 2 clinical trials to test efficacy in real patients. If the complete elimination of MELK will not affect the growth of cancer cells, only inhibit the function of MELK, what effect can it have?
Don’t say, it’s really effective! In cell experiments, OTS167 was added to kill cancer cells. More interestingly, OTS167 also has a powerful anti-cancer effect in cancer cells that knock melk out.
Based on this finding, the researchers reasoned that, first, OTS167 did inhibit the MELK protein. Second, the MELK protein and cancer cell growth has no relationship, without it, cancer cells still live well. Therefore, OTS167 must have played an anti-cancer effect through other unknown channels.
So is it a rare exception or a more common phenomenon to be skewed like OTS167? To answer this question, the researchers also looked at drugs that had less specific mechanisms. Intriguingly, they found 10 more similar examples.
This study has found 10 similar examples. References
“It is envisaged that these drugs should inhibit the action of certain proteins in cancer cells. In practice, however, most drugs do not work as reported. Professor Sheltzer commented.
You know, there are more than 180 papers that suggest these drugs should be effective. In addition, 29 clinical trials have been underway to assess the effectiveness of these drugs, with more than 1,000 patients being treated. Now, this study tells us that even if these drugs work, they work in a different way than we thought.
Some of the anti-cancer drugs may be working, may be a crooked . . . Pixabay
The scientists point out that the reason is the “off-target effect” in the early screening process. In the past, RNAi technology was often used to assess the importance of a particular target. However, RNAi technology has a potential off-target effect, which tends to inhibit the expression of other proteins. That is, when we think that a protein plays a role in killing cancer cells, it may be other proteins that really work.
For example, scientists have discovered a PBK protein inhibitor called OTS964, which is not important to the growth of cancer cells. Subsequent screenings found that OTS964 was also a powerful CDK11 inhibitor, which was all of a sudden: CDK11 was a class of proteins associated with processes such as gene transcription and chromosomal separation, and there had been no drugs that could target it. To be able to find its inhibitors, really can be said to be a mistake!
Researchers are looking for the true target spree of OTS964 by looking for “drug-resistant mutations” References
Some might say that no matter what black cat and white cat, it is the good cat that can catch the mouse. As long as it can kill cancer cells, whether it is mistakenly hit. The authors of this study disagree with this view – what we should do is improve the chances of drug success. Find targets that really affect the growth of cancer cells, and truly realize the potential of precision medicine.
“Many of the drugs used by cancer patients ultimately tragically fail to help these patients,” concluded Professor Sheltzer. “
Ann Lin et al. , (2019), Off-target is a common mechanism of action of cancer drugs under cancer drugs, Science Translational Medicine, DOI: 10.1126/scitranslmed.aaw8412
Many cancer drugs don’t’t hit fit intended targets: study, study, study, September Retrieve 11, 2019, from https://www.fiercebiotech.com/research/many-cancer-drugs-targets-are-misidentified-study-finds
Cancer drugs don’t always work as le, researchers warn, Retrieved September 11, 2019, from https://www.prnewswire.com/news-releases/many-cancer-drugs-may-not-work-as-thought-cshl-scientists-warn-300913114.html