Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Crispr Wins Key Approval to Fight Cancer in Human Trials

bloomberg.com

Post reply on HN
Print view View original

31–40 of 89 posts

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#31

Post by danarlow »

darawk wrote: post #17
astazangasta wrote: post #7

Earlier quoted context omitted.

People develop resistance to TKIs (tyrosine kinase inhibitors, the previous mode of therapy) within months; you could keep chasing the dragon, but the tumor is just going to keep doing the same thing, shedding whatever mutation you target. In this case you're not even targeting mutations that the tumor relies on (as you are with a TKI), so there's absolutely no fitness cost to the tumor to evade.

Could you simultaneously target multiple mutations to reduce the risk of this? Similarly to using a cocktail of antibiotics to prevent the development of resistance. i.e. the probability of shedding a single mutation is 1/x, but the probability of shedding two in the same organism is (1/x)^2, so targeting more mutations make it exponentially harder for the organism to adapt.

Yes, this reasoning is correct. Same principle applies to combination therapies for HIV, malaria, etc., where you're at risk of developing a resistant strain within the patient. Not sure why it isn't more common among cancer therapies. Maybe not enough unique targets?

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#32

Post by alextheparrot »

j_jochem wrote: post #27
baldfat wrote: post #24

Having lost a sister and a son to cancer I hope for this to work. The issues are tremendous for this technique and I don't have high hopes for its use on cancer. I am still having high hopes on immune system techniques that helps the body to mark cancer cells and attack the cells for most cancers. CRISPR big hope is that it can change the cell to stop reproducing or stop invading other cells. Simply put cancer cells…

Isn't the idea with CRISPR that you patch the patient's t-cells in such a way that they are able to recognize cancer cells as diseased cells, allowing the immune system to clear them away?

The holy grail would be fixing commonly occurring mutations that cause the cancer, but to my knowledge the edit/correction rate is too low for this to work currently, plus the possibility of causing more cancer by bad edits.

Thus, the T-cell approaches are more promising currently as it allows for direct modification of cells to fight cancer with known anti-cancer antigens, using a modified immune system.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#33

Post by themartorana »

Aelinsaar wrote: post #12
zymhan wrote: post #2

I hope that by the time I'm succumbing to the effects of aging, we'll have techniques with tools like CRISPR to make it easier.

It seems likely, assuming a couple of decades before you're "succumbing".

Who knows... Ain't that the mystery?

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#34

Post by themartorana »

darawk wrote: post #17
astazangasta wrote: post #7

Earlier quoted context omitted.

People develop resistance to TKIs (tyrosine kinase inhibitors, the previous mode of therapy) within months; you could keep chasing the dragon, but the tumor is just going to keep doing the same thing, shedding whatever mutation you target. In this case you're not even targeting mutations that the tumor relies on (as you are with a TKI), so there's absolutely no fitness cost to the tumor to evade.

Could you simultaneously target multiple mutations to reduce the risk of this? Similarly to using a cocktail of antibiotics to prevent the development of resistance. i.e. the probability of shedding a single mutation is 1/x, but the probability of shedding two in the same organism is (1/x)^2, so targeting more mutations make it exponentially harder for the organism to adapt.

Can you turn off a mutation's ability to adapt and mutate?

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#35

Post by maxander »

astazangasta wrote: post #4

I'm calling it here, this trial will fail hard. The basic idea is this: the cancer has a number of mutations that produce novel antigens that don't exist in normal cells. If we can train T-cells to recognize these, they can attack the tumor with great specificity and kill those cells. The problem is, all the tumor has to do to evade this targeting is shed the problematic mutation, which is easily done - tumors are gr…

Depends on what you mean by "fail hard," I suspect. Sure, cancer cells can gain or lose mutations, but if we target a mutation important for cancer development only a fraction of the target cancer will survive the treatment. We might achieve nice-to-have results like reduction in tumor size and increased patient life expectancy, or a "cure" in lucky patients with less agile cancers, which would put this radical new intervention in line with most standard cancer treatments. As a total cure for cancer it will "fail," but then, so have all the breakthrough cancer treatments that have collectively shattered the mortality rates of cancer patients.

(You mention you're involved in cancer research, so you presumably know all this already- I'm wondering if there's a more nuanced reason for this pessimism.)

The best theory I've heard so far as to how we'll "cure cancer" altogether is that we'll simply develop a big enough armory of anticancer treatments that no individual cancer case could evolve fast enough to beat them all. Unlike bacteria or viruses, cancers evolve on their own and when they're done their evolutionary innovations die with them. Our technology lives on, though, so we can hope to eventually just totally outclass their capabilities. If CRISPR gives us another source of these partial treatments, we're just that much closer to that level.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#36

Post by rudolf0 »

alextheparrot wrote: post #32
j_jochem wrote: post #27

Earlier quoted context omitted.

Isn't the idea with CRISPR that you patch the patient's t-cells in such a way that they are able to recognize cancer cells as diseased cells, allowing the immune system to clear them away?

The holy grail would be fixing commonly occurring mutations that cause the cancer, but to my knowledge the edit/correction rate is too low for this to work currently, plus the possibility of causing more cancer by bad edits. Thus, the T-cell approaches are more promising currently as it allows for direct modification of cells to fight cancer with known anti-cancer antigens, using a modified immune system.

Could this theoretically be used to fight all pathogen-based illnesses as well?

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#38

Post by robbiep »

rudolf0 wrote: post #36
alextheparrot wrote: post #32

Earlier quoted context omitted.

The holy grail would be fixing commonly occurring mutations that cause the cancer, but to my knowledge the edit/correction rate is too low for this to work currently, plus the possibility of causing more cancer by bad edits. Thus, the T-cell approaches are more promising currently as it allows for direct modification of cells to fight cancer with known anti-cancer antigens, using a modified immune system.

Could this theoretically be used to fight all pathogen-based illnesses as well?

Theoretically, it could be used to get a person to grow a new set of arms. But technology that doesn't exist yet is all speculation.

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#39

Post by robbiep »

danarlow wrote: post #31
darawk wrote: post #17

Earlier quoted context omitted.

Could you simultaneously target multiple mutations to reduce the risk of this? Similarly to using a cocktail of antibiotics to prevent the development of resistance. i.e. the probability of shedding a single mutation is 1/x, but the probability of shedding two in the same organism is (1/x)^2, so targeting more mutations make it exponentially harder for the organism to adapt.

Yes, this reasoning is correct. Same principle applies to combination therapies for HIV, malaria, etc., where you're at risk of developing a resistant strain within the patient. Not sure why it isn't more common among cancer therapies. Maybe not enough unique targets?

Not enough unique drugs, difficulty determining mutations/susceptibility of tumour to drug, high side effect profile of drugs used in isolation and higher still in combination

Re: Crispr Wins Key Approval to Fight Cancer in Human Trials

#40

Post by SapphireSun »

c-slice wrote: post #10

If you want to better understand the CRISPR patent dispute, this article lays out the arguments very clearly. https://www.statnews.com/2016/03/18/crispr-patent-dispute/

Ha, are you sure you didn't mean http://www.cell.com/cell/fulltext/S0092-8674(15)01705-5 ;D

(For those of you who aren't in on the joke, "The Heroes of CRISPR" was written by the director of the Broad Institute, which incidentally has Feng Zheng on its payroll. For that reason Eric Lander has been roundly criticized for attempting to weigh in on the history early. My friends who work in and around Kendall Square say that some of the criticism is overblown, the article points out a lot of people who didn't get much recognition prior, but still... it's a bit skeevy so you might want to take the latter half of the article with a grain of salt as it's not necessarily factually wrong, but the emphasis might be distorted and there is a risk of omissions.)

Post reply on HN