An LHRH receptor agonist + MTX as a treatment for prostate cancer?


Normally we don’t report on very early scientific research into possible treatments for prostate cancer because so many drugs just don’t even get into Phase I trials (let alone Phase II and Phase III). This possibility is a little different.

An article by Zhu et al. in the journal Scientific Reports has suggested combining an LHRH receptor agonist (a drug like Lupron or Eligard or Zoladex) with a very well known drug called methotrexate (an old drug with a long history as a disease-modifying agent in cancer, rheumatoid arthritis, and other disorders, commonly known as MTX). Their initial research has shown that a “bioconjugate” of this type has a high level of activity in vitro (i.e., in cell tissues in the laboratory) and in vivo (in laboratory mice) against prostate cancer. They conclude that such a bioconjugate “may be useful in the treatment of prostate cancer”.

Now we wish to be very clear that it might take years to prove this, and we are in no way suggesting that people should try the combination of methotrexate and an LHRH receptor agonist outside of some type of carefully controlled clinical trial. However, …

We do have a very good understanding of the risks and benefits associated with the use of methotrexate in the treatment of a number of disorders. We know how it works, and we understand its side effect profile. This is something that might be interesting … especially if it was to have a major impact on the progression of early metastatic prostate cancer.

2 Responses

  1. How did Snuffy miss this one … :<)) ??

  2. It should be pointed out that this is not simply a matter of administering an LHRH agonist and MTX together. What these guys did was hook the two molecules together to take advantage of the fact that some prostate cancers have LHRH receptors. The LHRH part of this drug latches onto the cancer cells, allowing much more targeted delivery of the MTX to the cancer cells.

    The LHRH part of this drug (actually an LHRH analog — not clear that it’s an agonist) doesn’t seem to have any role in suppressing the cancer, other than as a ligand.

    One has to wonder if this also concentrates MTX on the pituitary gland, which also has LHRH receptors.

    It seems to me that, as a cancer treatment, this is still extremely speculative.

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