Eli5 – Why do some cancer medications cause cancer?


I take a medication (Methotrexate) to treat rheumatoid arthritis. The drug is also used to treat cancer in higher doses. Certain types of cancers are a potential side effect. How does a medication used to treat cancer also potentially cause it?

In: 7

Cancer are cells that are damaged in just the wrong way so that they multiply in an uncontrolled way.

Methotrexate in high doses damages cells. It damages cells more the faster they multiply because it disturbs their mitosis, wich makes it good at killing the fast growing cancer cells.

Sadly your other cells aren’t fully immune, they have to multiply too, so they get attacked to some degree as well. Some will be killed, but a few of them might be damaged in the way they become new cancer. This will also especially hit your fast growing cells like in your spinal cord or your intestinal mucosa.

This is kinda why cancer is so nasty and hard to cure. It’s your own cells going haywire, so it’s difficult to design drugs that hit the cancer but not your healthy cells reliably.

Most of our chemical weapons against cancer mess with different steps in the process of cell reproduction, so that the rapidly-dividing cancer gets hit harder than the rest of you. In some cases, that includes directly reacting with DNA in ways that lead to cell death. This can also lead to mutations in vulnerable spots like bone marrow which can lead to things like leukemia. It’s also possible for a drug to have multiple effects unrelated to its main target.

It’s kind of hard to say. The mechanisms of action of MTX are just not entirely understood, it’s something of a black box drug. When used at high doses as a chemotherapeutic, MTX strongly interferes with a cell’s ability to produce the building blocks of DNA/RNA, and that means trouble when that cell enters the phase of replication where it must copy its DNA but finds itself short on materials. Generally when a cell is unable to continue replication normally, it has no other option than to call it off and go into apoptosis (controlled self-destruction). This sort of approach is common to many chemotherapeutics because cancerous cells are on average spending a lot of time replicating, so they’re susceptible to something that harms them mid-replication.

Now, as some of the other comments are saying, there’s always some possibility of survivable damage in a cell that wasn’t cancerous, but becomes that way because of it. But I would speculate in a different direction, because the association with increased cancer rates is also present when MTX is taken at much, much lower doses as an immunosuppressant for conditions like rheumatoid arthritis. Low dose MTX exerts quite different effects, and doesn’t interfere so broadly with DNA building block production –> possibility of survivable DNA damage. How it works instead then is *also* not entirely understood, but it’s thought to involve a more subtle interference that keeps T- and B cell activation down. That can be desireable when those are causing an autoimmune disease like RA… but they are also responsible for detection and killing of cancerous cells before they get out of hand, particularly T cells.

So to summarize a bit, yes, MTX is used as a chemotherapeutic in cancer, but at different dosage it can do different things — namely, become more of an immunosuppressant (though since these immune cells are also rapid multipliers, high dose MTX hits them too!). And immunosuppression in general can make you more susceptible to developing various cancers, because your immune system is normally in charge of killing off cancerous cells before things get out of hand. You’ll see the same thing with other immunosuppressant drugs used to treat rheumatoid arthritis, like TNF inhibitors.

The basic idea of treating cancer is that cancer cells are weaker than normal cells. So you try to damage cells, aiming for the specific area with cancer, just enough so that it kills cancer, but it does not kill many normal cells. The reality is that you are gonna have some normal cells hit by whatever method you use, and that can itself cause cancer.

Because it just so happened what someone testing it developed a different kind of cancer. So they have to include it in the side effects whether it was actually caused by the specific medication or not. Some of the medications with “death” listed as a side effect are from people dying of auto accidents during trials. Anything that happens during a trial has to be included whether it can be proven or not.