The clinical trial that Give 1 For Dad will be working to fund is complicated and a detailed description is below. For those of us without medical degrees, here’s a simplified explanation.
Prostate Cancer needs copper—in fact, it’s a glutton for copper and will consume all it can get. This clinical trial will be designed to exploit that as a weakness using a FDA-approved and generally well-tolerated drug called disulfiram. This drug is highly toxic to Prostate Cancer, but not to the rest of the body. It is also essentially attracted to copper. While still being designed, the general approach of the study will be to give the Prostate Cancer all the copper it wants and then let this drug find the copper. The study will evaluate the effectiveness of the drug in killing the copper-filled cancer and any side effects to patients that might result. Trials involving generic drugs have an incredibly tough time getting funded, but when fully designed this trial may represent an important new strategy for treating Prostate Cancer.
The preclinical work providing evidence for this trial has been published and can be found here: Copper transport in prostate therapy Cancer Research 2014
Please help us get it tested.
Using Copper to Sensitize Prostate Cancers to a “New” Treatment
For advanced prostate cancer patients who develop recurrent cancer after local therapy, or are diagnosed with cancer that has spread to other parts of their body, our treatment options are limited. Most patients will undergo sequential treatments of hormonal or chemotherapy. Hormonal therapies in prostate cancer decrease testosterone and related androgens or block them from binding to proteins (receptors) in cells that turn on genes to help prostate cancer cells divide and grow. When the cancers become resistant to these treatments, we are largely left with chemotherapies – cellular poisons designed to kill cells that are rapidly dividing or genetically unstable. While modestly effective in many patients, they come at a cost to the health, well-being, and quality of life of the patient.
In prostate cancer, the androgen receptor turns on genes that make key proteins required for cells to absorb copper in high concentrations. We first thought to block copper in cells with drugs that would bind it all up but this was difficult to accomplish and not completely effective. Then, instead of inhibiting copper, we sought to screen for drugs that killed cancer cells only in the presence of copper. We identified disulfiram (DSF), which is an approved drug for treatment of alcohol abuse. In the absence of alcohol it is well tolerated with only minor side effects. In our prostate cancer models, DSF blocked the growth of cells and caused them to die when copper was present. When we took copper away, the drug no longer worked. Not surprisingly then, when DSF alone was given to patients with prostate cancer, the drug didn’t do much.
We have studied the copper-DSF activity extensively in the laboratory and have shown that (a) the anti-tumor effect is increased, not reversed, by adding excess copper, (b) copper is the only element that is an effective partner for DSF, and (c) the effects occur even with low doses of DSF, far lower than previously thought to be needed to kill cells with this drug. All together these results suggest that DSF may be far more effective against prostate cancer if we can increase the copper concentrations within tumors of patients with widespread disease. Based upon these observations we hypothesize that excess exposure to copper will trigger disease response to DSF with minimal side effects in patients.
To test our theory we propose a Phase I study to look at the treatment effects and side effects of DSF in advanced prostate cancer patients using increasing doses of intravenous copper before treating patients with DSF by mouth. Because copper is poorly absorbed in the intestines, we will need to give copper intravenously.
The first goal of our study will be to show the safety, tolerability, and best dose of intravenous copper followed by DSF. We will perform a new kind of nuclear medicine scan, called a positron emission tomography (or PET) scan that follows a tiny dose of radioactive copper when injected intravenously in patients to measure how much copper the tumors take up. When possible, we will also measure copper levels and the androgen receptor activity in patients who agree to undergo a tumor biopsy. We will use these tests along with blood levels of copper to determine the best dose for further testing. Of course, our other goal is to describe any positive treatment effects in patients to the combination of intravenous copper and oral DSF.
Together these early results will provide critical data to allow us to gain support for new drug formulations of DSF and both federal and industry support for further development of this exciting new and potentially minimally toxic treatment of prostate cancer.