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Rendered at 10:01:09 GMT+0000 (Coordinated Universal Time) with Vercel.
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.
CRISPR is a great tool, but it doesn't help with delivering gene therapy across the body.
How about for lymphomas?
In a parallel universe, it would be hard to imagine that much money not altering the reported results significantly.
So, in biology a gene's name is sometimes an acronym but it's meaning is generally forgotten
> TIGIT (/ˈtɪdʒɪt/ TIJ-it;[5] also called T cell immunoreceptor with Ig and ITIM domains) is an immune receptor present on some T cells and natural killer cells (NK).
And the overall premise is spot on: while it’s a shame that the drugs failed, it’s okay, because we want companies to be taking bets on targets that might result in the next big drug to save or prolong lives.
> In 2026, a BMJ Oncology analysis would give a clinical name to what had happened: “herding.” The authors estimated that nearly 49,000 patients had been enrolled in anti-TIGIT trials by pharmaceutical companies, at a cost of more than $3 billion, all because their fellow pharmaceutical companies were doing the same thing
This is also spot on. I’ve been in the room when people have been infected by this peculiar competitive mania. Rational science takes a backseat to FOMO. But it’s also somewhat understandable: the model we have relies on companies making money to continue to exist and invest in further research and drug development. So of course, they all wanted a slice of the pie, no matter how wrong this was in retrospect. It’s just how the current system works, and it’s the least bad (?) system we’ve yet evolved for such sharing out of resources.
Is the herd effect wrong? This is not a simple question to answer with objective pareto-optimal answers for everyone.
If the promising direction pans out, having 3-5 drugs in the pipeline represents a far faster optimization problem, with far faster discovery, leading to more years of lives saved. Going slow, waiting for one drug to succeed or fail, learning maximally, then maybe trying another, may be dollar optimal, but has other risks: abandoning a good direction too early because of stochastic decision making (see for example the story of GLP-1 agonists which were delayed for decades because of optimizing to avoid me-too diabetes injectables), and also not exploiting a very promising target that pans out well in the first trial.
The speed issue is also one reason that trials are so expensive, and why drug discovery is limited in what we can try. If there were lower barriers to entry for trials--that somehow maintain the same safety characteristics--then perhaps we could learn faster and better and more cheaply. And the quote talks about a very important thing: there's only so many data points we can collect because there's only so many people who can ethically go on to a clinical trial in the first place. How we optimize the best outcome for those clinical trial patients, and the best outcome for society in general from what we learn from the trials, does not have a clear and obvious answer. This is why ethics classes belong in the curriculum of all advanced bio degrees, IMHO!