Comment by hentrep
2 years ago
Disclaimer: Haven’t read the article.
Radiation has benefits that your chemical cytotoxics do not. An individual tumor often comprises of many subclonal cancer cell populations, all of which could have unique resistance mechanisms to allow that subclone to survive and proliferate in the presence of a single cytotoxic payload (say from an antibody-drug conjugate).
Targeting cancer cells with a radioactive payload can bypass many resistance mechanisms common to cytotoxic payloads.
Pluvicto (lutetium-177) is one of the hotter radioligand therapies as of late (approved for metastatic prostate cancer). Take a look at Fig 1a here - the responses can be quite striking for patients with extensive metastatic disease: https://www.frontiersin.org/articles/10.3389/fnume.2023.1291...
What I find most interesting are the supply chain challenges and logistics for radioligand therapies. Given the half-life of the payload, this is not something one can just manufacture and set on a shelf for the next patient. And of course the regulations involved with anything radioactive provide additional challenges.
> Radiation has benefits that your chemical cytotoxics do not. An individual tumor often comprises of many subclonal cancer cell populations, all of which could have unique resistance mechanisms to allow that subclone to survive and proliferate in the presence of a single cytotoxic payload (say from an antibody-drug conjugate).
Interestingly cancers can develop resistance to radiation induced cell damage as well.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914062/
It's been known for a while since distal metastases would develop when primary tumors were treated with radiation.
What might be interesting is dual treatment - use a cytotoxin-link and radionuclide-linked antibodies together. No idea if it's been tested, but it's an obvious approach since combination therapy is being attempted with damn near every cancer therapy.
I get that radiation is generally biocidal, but so are a lot of things.
Following the reasoning of the parent comment,
> It's seems to me, as a layman, that the hard part would be designing the "targeting" end of the drug
It fits nicely with this statement:
> An individual tumor often comprises of many subclonal cancer cell populations, all of which could have unique resistance mechanisms
If the unique features of a tumor cell are the lock, then your search space has a relatively small number of keys, compared to a larger toolkit of known biocides. The key needs to fit a specific cancer cell, while the biocide merely needs to avoid the cancer cell’s needle-in-a-haystack resistance mechanisms, which are tailored for surviving in the human body rather than against laboratory chemicals. The harder problem seems to be finding the one or more keys needed to target a diverse population of cancer cells.