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FDA has approved many purine analogs e.g. thioguanine, cladribine, pentostatin, mercaptopurine for various forms of leukemia and/or lymphoma, but none for non-hematological malignancies. What makes non-hematological malignancies untreatable by purine analogs?

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It's not a given, that they are not useful in solid tumors (also lymphoma are accounted among the solid tumors).

There are pyrimidine-like antimetabolites, e. g. 5-FU: https://en.wikipedia.org/wiki/Fluorouracil, while some purine antimetabolites were in development, see e. g. here: https://www.ncbi.nlm.nih.gov/pubmed/4066218.

There are some approaches that try to make tumors more sensitive to purine antimetabolites, e. g. https://www.sciencedirect.com/science/article/abs/pii/S0006295219304691.

Another, older, paper that describes a purine antimetabolite in lymphoma: https://ascopubs.org/doi/abs/10.1200/JCO.1991.9.1.175

A more recent approach on the purine metabolism: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01697/full

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    Thanks, but I was asking specifically about purine analogs. Pyrimidine analogs useful in solid tumors are well known for 60+ years. Mar 30 '20 at 21:36
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    Also that paper is from 1985. If you have a more recent reference for purines in development for solid tumors, I'd be happy to take a look. Mar 30 '20 at 21:36
  • Still looking into things, will edit my answer as things progress.
    – Thomas
    Mar 30 '20 at 21:45
  • Thanks. I'll have to make a correction: I wasn't aware that lymphoma is sometimes classed as a solid tumor, so I'll just edit the question and replace "solid tumors" with "non-hematological malignancies". There are indeed several purine analogs approved for the treatment of lymphoma. Mar 30 '20 at 21:57

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