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Medical Inspiring Malignant Melanoma Phase I Clinical Trial Story: NY Times

  1. Feb 28, 2010 #1


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    From New York, Dr. Paul B. Chapman of Memorial Sloan-Kettering Cancer Center, perhaps the most determined skeptic of the group, acknowledged, “This looks impressive.”

    The trial of PLX4032 offers a glimpse at how doctors, patients and drug developers navigate a medical frontier as more drugs tailored to the genetic profile of a cancer are being widely tested on humans for the first time.

    Throughout the fall, the only two patients on the trial whose tumors continued to grow were the ones who did not have the particular gene mutation for which the drug had been designed. They were removed from the trial. By late December, tumors in the 11 patients who did have the mutation had shrunk. Those involved in the trial held their collective breath waiting to see how long the remissions would last.

    http://www.cancerhelp.org.uk/trials/types-of-trials/phase-1-2-3-and-4-trials" [Broken]

    Inspiring story, especially the one about Chris Nelson who was almost not eligible for the trial. Scroll down and watch the video.

    Last edited by a moderator: May 4, 2017
  2. jcsd
  3. Feb 28, 2010 #2


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    There is a recent paper in Nature that gives more insight into the mechanism of action of the drug: http://www.nature.com/nature/journal/vnfv/ncurrent/pdf/nature08902.pdf".
    In short tumors with mutated BRAF are dependent on the RAF–MEK–ERK pathway. The inhibitor works by inhibiting RAF. Previous clinical trials have been done by inhibiting MEK, but treatment is limited due to toxicity. Surprisingly inhibition of RAF by the compound does not lead to reduced levels of MEK in wild-type cells, but even higher levels (due to drug-mediated transactivation of RAF dimers). This allows for the administration of a high dose of the inhibitor and a stronger inhibition of the ERK pathway in the BRAF-mutated tumor cells. Drug resistance does develop, due to activating mutations in BRAF, RAS or RAF.

    I'm curious about the follow-up clinical studies with this new compound.

    There are other studies that target specifically the melanin pathway, where the zebrafish is used as a model organism. They specifically could eliminate the melanoma and other melanin-producing cells, but I wonder what the side-effects would be in humans (albinism?).
    Last edited by a moderator: Apr 24, 2017
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