3 ms·

At the same time we see TIGIT targeted drugs failing, we are seeing the success of drugs against another white whale of cancer drug targets: KRAS. It's the mos

At the same time we see TIGIT targeted drugs failing, we are seeing the success of drugs against another white whale of cancer drug targets: KRAS. It's the most frequently mutated cancer activating gene out there, but has been declared "undruggable" for the 15-20 years I've been close enough to drug developers to have heard about it. Yet we're seeing clinical successes in recent trials with Revolution Medicine's daraxonrasib, and now there's blood in the water, with tons of new approaches going after it. The progress in biotech in the past few decades has been unbelievable, and lots of things that were considered impossible a few decades ago are now happening left and right. Whenever I hear that somebody thinks that technological progress has stopped, I just think that they've stopped looking in the right places for the huge advances that are going on.

mft_ 5mo ago
Agree. It's incredible that for pancreatic cancer (which is one of the single-most lethal and difficult-to-treat cancers there is) we're moving from a choice between a couple of decade-old and brutal chemotherapy cocktails, to discussions about sequencing and even the possibility of chemotherapy-free treatment, in a single generation of new agents.
strbean 5mo ago
What's the status of just using CRISPR to fix pathogenic variants?
- epistasis 5mo ago
  For fully formed humans? Not great, with exceptions where you can target a 2D layer of cells that are covered in fluids. I've seen some people trying this with, say, retinas, where you only need to target some of the cells. And also with intestinal/colorectal linings, where cells reproduce quickly so there's a chance of actually replacing all of the cells eventually. But for most of the body, I don't think anybody has ever been optimistic about CRISPR fixing pathogenic variants. CRISPR is a great tool, but it doesn't help with delivering gene therapy across the body.
  - strbean 5mo ago
    So for masses of solid tissue, we can't effectively deliver the payload to all the cells? How about for lymphomas?

mft_ 5mo ago

Agree. It's incredible that for pancreatic cancer (which is one of the single-most lethal and difficult-to-treat cancers there is) we're moving from a choice between a couple of decade-old and brutal chemotherapy cocktails, to discussions about sequencing and even the possibility of chemotherapy-free treatment, in a single generation of new agents.

strbean 5mo ago

What's the status of just using CRISPR to fix pathogenic variants?

epistasis 5mo ago
For fully formed humans? Not great, with exceptions where you can target a 2D layer of cells that are covered in fluids. I've seen some people trying this with, say, retinas, where you only need to target some of the cells. And also with intestinal/colorectal linings, where cells reproduce quickly so there's a chance of actually replacing all of the cells eventually. But for most of the body, I don't think anybody has ever been optimistic about CRISPR fixing pathogenic variants. CRISPR is a great tool, but it doesn't help with delivering gene therapy across the body.
- strbean 5mo ago
  So for masses of solid tissue, we can't effectively deliver the payload to all the cells? How about for lymphomas?