• Question: Can we overcome tumor resistance to platinum-containing antineoplastic drugs by activating the sensitivity factors in the tumor?

    Asked by anon-329023 on 29 Jun 2022.
    • Photo: Sophie Richardson

      Sophie Richardson answered on 20 Jun 2022:

      I’m going to be honest with you, I’m not sure as I don’t know much about platinum-based treatments for cancer. I’ve found a scientific review article that says “The [platinum-based treatment] resistance result[s] from (i) reduced cellular drug accumulation, (ii) increased detoxification system, (iii) increased DNA repair process, (iv) decreased apoptosis, and (v) autophagy” Zhou et al. (2020) (here’s the link if you are interested https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100275/ ).

      From this information, targeting any of these five mechanisms of resistance might help to reverse tumour resistance to this type of treatment. I think even scientists are still figuring this one out, so great question!

    • Photo: Karin Purshouse

      Karin Purshouse answered on 20 Jun 2022:

      Hi, so as we discussed in the chat, I think a lot of the same principles that apply to platinum based chemotherapies would apply to other types of chemo – although chemo drugs all work in slightly different ways, they all generally cause rapidly growing cells like cancer cells to stop being able to grow and be unable to survive.

      Fun fact – some chemo types that we still use today are made from plants or the bark of certain trees!

      So what happens when cancer cells no longer respond to chemo? Well, you’re right that it means cancer cells are resistant to that particular type of blockade. Our approach now is to try another drug from another family – in hopes that this will find the sensitivity of the cancer. But we don’t yet do this in a very specific way. Hopefully in the future, when patients become resistant to certain treatments, we can test their tumours and find out what they might be sensitive to!

    • Photo: Timothy Budden

      Timothy Budden answered on 1 Jul 2022:

      My PhD was actually on this topic, I worked in melanoma which very rarely ever respond to platinum chemotherapies so they are rarely used. My interest was in DNA repair which is faulty in melanoma and as platinum chemotherapies damage the tumour DNA I was looking at if we could switch the repair mechanisms back on would the tumour cells then respond to the treatment.

      I combined platinum chemotherapy drugs with DNA demethylating agents. DNA methylation is a modification to the DNA structure (that doesn’t effect the sequence of the DNA) that can control gene expression. So the idea was to “reset” the expression of DNA repair genes to normal and then treat with platinum chemotherapy. This actual did result in more cell death and decreased growth in melanoma cells. Just after I had finished my PhD my supervisor had set up a collaboration with a local oncologist and they now have a clinical trial running that combines these drugs with immunotherapy as well to overcome resistance.

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