3 ms·

This seems too straightforward to be credible? If I was researching in this field surely this is the first thing I’d try? If it is indeed credible … this sound

This seems too straightforward to be credible? If I was researching in this field surely this is the first thing I’d try? If it is indeed credible … this sounds like the “CRISPR moment” of cancer treatment, sure. And I’m really happy for that. But I will be honest and write what I’m thinking: if this is real then frankly I’m disappointed it took this long. Do we really have our best people working on cancer? I have known so many who died waiting. It seems like there has been roughly the same investment this decade (around $200B) in climate tech compared with cancer research, and yet electric cars and batteries are now a “solved problem” that’s just waiting to scale. The progress with Cancer is noticeably less. Is the money being well spent? Or are we donating $100B-s for researchers and labs to sit on a gravy train making sub tier progress. Here’s a wild theory. Perhaps as a society we built the wrong prerequisites to get into cancer research and we filtered out all the Mozart’s and Leonardo’s…

pama 2y ago
I work in this area. It took time to know what each protein does in a cell (we still dont really understand most of them), it took time to find all the ways that various cancers use the protein machinery in the cell to their benefit (new ways are still being discovered these days), it took time to think about molecular glues and turn them practical, and it took time to build the right chemistry and then test it (it takes time even after you know all of the previous steps.) It will still take years, possibly over a decade before this particular development can lead to a drug that passes human clinical trials and is eventually approved. It is not the lack of geniuses that slows things down, rather it is the very careful consideration of risks to minimize the loss of human life during experimentation, and the attempt to optimally allocate the resources across too many different challenging problems in order to maximize the long term benefit to society. The true amount of money spent in cancer research is much higher than the $200B over a decade that you mentioned, however the vast majority of it is just capital losses of various companies spent on the tools and research in early stage discovery across tens of thousands of projects, and a separate huge and more obvious chunk goes to attempts and failures at human clinical trials. The cost of drug discovery has stopped increasing exponentially during the last decade but is still pegged at several billion dollars per approved drug without counting costs from competitors who never get anything approved.
krisoft 2y ago
> If I was researching in this field surely this is the first thing I’d try? Let me ask a clarifying question: Are you saying that the first thing you would have tried is to synthesize bivalent molecules that link ligands of the transcription factor B cell lymphoma 6 (BCL6) to inhibitors of cyclin-dependent kinases (CDKs)? Or are you just saying that you would have tried to drive cancer cells to self-destruct (but have no clue how)?
- aetherspawn 2y ago
  With a little domain knowledge and research you find out pretty quickly that: BCL6 is lymphoma. CDK regulate cell death, amongst other things. So yes, I am saying that it seems very straightforward as an approach to attempt to trigger a CDK cell death when BCL6 is present. It seems hard to believe that it is presented as novel with the amount of funding that has been spent on cancer.
  - krisoft 2y ago
    > With a little domain knowledge and research you find out pretty quickly That's cool. Where do you think that domain knowledge comes from? Did we just found it in a fortune cookie? Or does the cancer research conducted has something to do with that we have this knowledge? > BCL6 is lymphoma. That's not correct. BCL6 is a protein, or a gene which codes that protein. Mutations in BCL6 can lead to B cell lymphomas. BCL6 is not lymphoma. > I am saying that it seems very straightforward as an approach to attempt to trigger a CDK cell death when BCL6 is present. Excellent. Sounds like you are an oracle of oncological research roadmap. What should be the next target to develop drugs for?
    - aetherspawn 2y ago
      I am glad that you know these things, but cancer research has still failed society as a whole. 3 of my immediate family have had cancer, 2 took chemo and it ruined their lives (it caused weak bones, their spines to virtually dissolve, which led to surgeries to insert plates and things, which have failed multiple times, it has been a mess). The third was not eligible for chemo because they were too sick and they had an existing case of lupus. So we started trying things -- probably 100 different things at first. What worked for them is taking Sanguinaria canadensis daily orally. It is now 15 years later and they still have cancer but are living a normal and healthy life. You know, despite being the most effective treatment you could possibly hope for in this situation (besides an actual cure), there are only a few papers on Sanguinaria canadensis, and most research discredits it. Other friends of mine have tried chemo and died in a horrible way. Now you understand my criticism of cancer research. For all the money that has been spent, the most viable treatment available through a hospital is still a living nightmare.

pama 2y ago

I work in this area. It took time to know what each protein does in a cell (we still dont really understand most of them), it took time to find all the ways that various cancers use the protein machinery in the cell to their benefit (new ways are still being discovered these days), it took time to think about molecular glues and turn them practical, and it took time to build the right chemistry and then test it (it takes time even after you know all of the previous steps.) It will still take years, possibly over a decade before this particular development can lead to a drug that passes human clinical trials and is eventually approved. It is not the lack of geniuses that slows things down, rather it is the very careful consideration of risks to minimize the loss of human life during experimentation, and the attempt to optimally allocate the resources across too many different challenging problems in order to maximize the long term benefit to society. The true amount of money spent in cancer research is much higher than the $200B over a decade that you mentioned, however the vast majority of it is just capital losses of various companies spent on the tools and research in early stage discovery across tens of thousands of projects, and a separate huge and more obvious chunk goes to attempts and failures at human clinical trials. The cost of drug discovery has stopped increasing exponentially during the last decade but is still pegged at several billion dollars per approved drug without counting costs from competitors who never get anything approved.

krisoft 2y ago

> If I was researching in this field surely this is the first thing I’d try? Let me ask a clarifying question: Are you saying that the first thing you would have tried is to synthesize bivalent molecules that link ligands of the transcription factor B cell lymphoma 6 (BCL6) to inhibitors of cyclin-dependent kinases (CDKs)? Or are you just saying that you would have tried to drive cancer cells to self-destruct (but have no clue how)?

aetherspawn 2y ago
With a little domain knowledge and research you find out pretty quickly that: BCL6 is lymphoma. CDK regulate cell death, amongst other things. So yes, I am saying that it seems very straightforward as an approach to attempt to trigger a CDK cell death when BCL6 is present. It seems hard to believe that it is presented as novel with the amount of funding that has been spent on cancer.
- krisoft 2y ago
  > With a little domain knowledge and research you find out pretty quickly That's cool. Where do you think that domain knowledge comes from? Did we just found it in a fortune cookie? Or does the cancer research conducted has something to do with that we have this knowledge? > BCL6 is lymphoma. That's not correct. BCL6 is a protein, or a gene which codes that protein. Mutations in BCL6 can lead to B cell lymphomas. BCL6 is not lymphoma. > I am saying that it seems very straightforward as an approach to attempt to trigger a CDK cell death when BCL6 is present. Excellent. Sounds like you are an oracle of oncological research roadmap. What should be the next target to develop drugs for?
  - aetherspawn 2y ago
    I am glad that you know these things, but cancer research has still failed society as a whole. 3 of my immediate family have had cancer, 2 took chemo and it ruined their lives (it caused weak bones, their spines to virtually dissolve, which led to surgeries to insert plates and things, which have failed multiple times, it has been a mess). The third was not eligible for chemo because they were too sick and they had an existing case of lupus. So we started trying things -- probably 100 different things at first. What worked for them is taking Sanguinaria canadensis daily orally. It is now 15 years later and they still have cancer but are living a normal and healthy life. You know, despite being the most effective treatment you could possibly hope for in this situation (besides an actual cure), there are only a few papers on Sanguinaria canadensis, and most research discredits it. Other friends of mine have tried chemo and died in a horrible way. Now you understand my criticism of cancer research. For all the money that has been spent, the most viable treatment available through a hospital is still a living nightmare.