My dad researched doing exactly this for 30 years. They had several treatments go to clinical trial, though I believe none of theirs have gone forward.

It's known as gene therapy: https://en.m.wikipedia.org/wiki/Gene_therapy

The same lab used a genetically modified virus to develop an oral rabies vaccine that is in wide use today.

This was dad's boss: https://nrc.canada.ca/en/stories/foundations-discovery-honouring-work-canadian-researcher-dr-frank-graham

There are in fact ways to modify viruses to make them preferentially target cancer cells in a more "general" or non-specific way (the technical term would be antigen-agnostic).

• These viruses are known as oncolytic viruses and are a major field of study in cancer immunotherapy/virotherapy. Many of these viruses are rhabdoviruses (same family as rabies, but obviously not rabies), vaccinia viruses (pox viruses), or herpes viruses. Every nucleated cell in the body has an internal anti-viral response that result in expression of viral-response genes to alter the cell (such as initiating cell death to prevent virus spread) and release interferon proteins to alert the immune system and prime antigen-presentation.

Many cancer cells actually have disruptions and mutations in these pathways so that they do not have as robust an anti-viral response. This can be exploited with oncolytic viruses.

To exploit this the virus can be genetically engineered to lack its own anti-immune system genes that interact with those interferon response genes.

• For example, VSV (a rhabdovirus) can be modified with a mutant M gene so that it is more sensitive to the interferon proteins and response pathways. So using such a virus, normal healthy cells which have a proper anti-viral response can be infected by this VSV M-mutant but it is not productive and the virus wont replicate more than once in those tissues. However in cancer cells with the defective interferon pathways, the viruses does attain productive replication and can kill the tumor cell.

• The second important aspect of this is the virus alerts the host immune system to its presence within the tumor, results in spreading of mutated antigens from the tumor, and can then trigger a stronger immune response against the tumor itself. This is a huge field and is leading to oncolytic viruses as a vector for both direct anti-tumor toxicity and immunotherapy/vaccination.

There is currently 1 FDA approved oncolytic virus treatment: T-vec

My research is not on oncolytic viruses but I have some knowledge, the modern space of oncolytic viruses has likely advanced quite a bit and other viruses may be better choices than say VSV.

Source: PhD in immunology. For further reading refer to these articles

Oncolytic viruses for cancer immunotherapy

Engineering strategies to enhance oncolytic viruses in cancer immunotherapy

Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer

There are currently attempts to sort of do that, but it isn't usually as simple as modifying the virus to infect cancer cells. I'll explain more about that in a second. First, as far as a challenge to doing this that you asked about, the big one is that cancer cells are very similar to your healthy cells. It's difficult to produce a virus that would reliably target cancer cells without also infecting at least some of your healthy cells somewhere in your body. Cancer cells are human cells, so it isn't the same as something that targets bacterial cells.

That said, one method in gene therapy studies nowadays is to use viruses as vectors to deliver genes to cancerous cells. Simple retroviruses, for instance, infect dividing cell populations. Since cancer cells are actively dividing, retroviruses will infect them. One method is to engineer a retrovirus with an enzyme that will convert a 'prodrug' to a compound which will kill the cell. The problem is, if you're going to genetically alter a virus and put it in someone, you want to have a failsafe in place to prevent it from replicating and spreading. So, these viruses are then engineered to be replication defective...meaning they'll inject their RNA into cells and integrate it into the host genome, but will lack the genes needed to commandeer the cell and create more replicating viral copies. These replication defective viruses are grown in what are called "packaging cells" which are themselves altered to contain the genes that the modified viruses lack. (This way, packaging cell lines create the altered virus, which is then incapable of replication in normal cells). There's always the risk that these viruses could regain replication competence through various means, so they're engineered in a way to minimize this risk, and screening for viral shedding and replication competence should be performed to make sure it isn't happening. There are other ways to approach this with viruses other than retroviruses but this comment is already long enough lol.

Point is, it's being worked on but is very complicated so will take time, and may never become the 'silver bullet' that you'd expect. (Fingers crossed tho!)

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There's an XKCD summarising a genuine scientific study into this exact idea from 2011 https://xkcd.com/938/

They developed a technique to genetically modify the immune cells of a patient's own body to make them target the cancer cells. They used a virus to genetically modify the immune cells and there's one kinda famous virus that scientists have been studying in detail for a while which already modifies immune cells. They used genetically modified HIV to supercharge the immune system to fight off cancer.

I haven't read the original study so I don't know how successful it was.

It is original idea of tumor immune gene therapy. You isolate the cancer cell, put part of it in a virus (usually Adenovirus) and infect the humane cells. It is a fairly easy process. the difficulty is to select the best part of the DNA used as antigen

This is done since the mid 1990s, with mixed results.

This is also what the Astra Zeneca Covid vaccines is using.

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So the general idea behind immunotherapy cancer treatments (I believe) is using pathogens, such as viruses to to mark/tag cancerous cells so your immune system knows to target those cells and not healthy ones. Which is kinda like you are describing except we aren’t using the pathogens to directly attack cancer cells. Or something like that

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Yes, in addition to what others have mentioned the other way to do it is to make a virus that can *only* replicate in cancer cells.

So the cancer cells aren't being directly targeted, but the mutant virus can't replicate in normal cells. Presumably when the virus enters non-cancerous cells it just gets quietly degraded during general protein and nucleic acid turn-over

This may sound weird at first. However, There is some overlap with the way some cancer cells and some viruses need to be able to disrupt the cell to replicate effectively.

Most cells in an adult are senescent or dividing very slowly, so all the machinery for DNA replication and spare bases are are at low levels.

Cancer cells divide by definition, and viruses tend to evolve to sort of force cells into dividing or dividing faster, so that they will then be able to replicate faster.

If these things get "turned on" when they shouldn't most cells will commit suicide (apoptosis) with the help of "checkpoint proteins" and other mechanisms. Cancer cells tend to have mutation in these checkpoints (which is why they don't commit suicide).

So one can imagine a scenario where you have a cancer with a known checkpoint mutation, and a virus that targets the same checkpoint protein (with one of the viruses numerous genes/proteins).

If you remove or mutate the gene in the virus that targets that checkpoint, the virus will only be able to replicate in cells that have a defective checkpoint.

I saw talks back in the late 90s where they had a few great results with inoperative head and neck tumors, but there were too many complications and deaths.

Soviets followed that line of inquiry during the cold war. Dont remember why they stopped. Most likely a combination of funds running out, political upheaval, and capitalism prefering antibiotics and antiviroids because they are better for profit.

No, the mutations that occur in your regular cells are basically mutations in the mechanisms that control cell division and/or cell death. So they keep growing, causing a tumor. For the most part, they still look like the same cell on the outside. That’s what your body doesn’t mount a strong immune response and it is hard to target them with drugs. All the houses look the same, there’s no way to give the bacteriophage an address.