DNA damage

But what's interesting about this guy is it encodes something called colibactin, and colibactin is- I wouldn't say it's really an antibiotic in the classic sense because it can be kind of damaging, but bacteria can use it for defense.

Um, it's encoded in some E. coli species, and it causes DNA damage in other organisms.

And in fact, it just is an alkylating agent, and it, uh, cross-links strands, and then you end up with d- double strand breaks during replication, and cell cycle arrest, and cell death.

So it's, it's good.

Hmm

...

I mean, it makes sense though in the sense that if they're c- with colorectal cancer, that's DNA damage probably induced, and that the colibactin is alkylating DNA.

It's probably not specific to bacteria.

The tumor can restore DNA damage and resistant subpopulations of the cancer can persist and the disease can return.

The field had recognized this a long time ago.

You know, there are other possible targets in DNA damage response, and that space is pretty crowded with active programs directed at ATR or ATM or WeOne, CheckOne, PollQ.

You know, investors that are familiar with this space would be familiar with those targets as well.

And several of them are from well-capitalized companies.

But after more than a decade of investigation, PARP remains the only DNA damage response target with an approved agent in any jurisdiction.

So PARP also carries an important limitation.

It's tied to homologous recombination deficiency.