Finding Anticancer Drugs in Unlikely Places
Finding Anticancer Drugs in Unlikely Places
Hello. I'm Dr. Maurie Markman, from the Cancer Treatment Centers of America in Philadelphia.
I want to discuss a very interesting question in the area of precision or genomic medicine in the cancer arena. This is sort of an interesting twist on the question of the use of anticancer agents that have not been approved by the US Food and Drug Administration (FDA) for a particular malignancy.
Usually, we're talking about a drug that might have been approved for the treatment of a particular condition -- but it's an anticancer agent. It might be used for breast cancer, and lo and behold, we find that there might be some activity (at least in theory) in lung cancer or perhaps in a hematologic malignancy because a particular molecular marker that is present in the tumor -- for example, HER2 overexpression -- might be present not only in breast cancer, but also in lung cancer or even lymphoma.
But what we're talking about is an anticancer agent approved for the use of treatment of a cancer and perhaps used in another malignancy.
The question to be asked in this brief discussion is this: What if one were to find a molecular marker that appears to be relevant in the treatment of cancer and, through preclinical evaluation, one finds that a drug that had been approved for an entirely different purpose -- having nothing whatsoever to do with the treatment of cancer -- also appeared to affect that particular molecular target? One might ask the question, is it possible that a drug that is given for a tumor type where there was a particular molecular abnormality, but is not currently used in the treatment of malignancy, might be effective in that situation?
We have a very interesting example, at least in a preliminary way, of where that might be quite relevant. It turns out that in the treatment of metastatic or advanced basal cell carcinoma, there is a molecular pathway known as the "hedgehog pathway" that appears to be quite relevant in the progression of that malignancy. In fact, there has recently been a drug approved specifically for the treatment of advanced metastatic basal cell carcinoma on the basis of the presence of that pathway.
It turns out that the antifungal agent itraconazole also affects the hedgehog pathway. In a very interesting article in the March 10, 2014, issue of the Journal of Clinical Oncology, investigators report on a phase 2 trial of the use of oral itraconazole in the treatment of basal cell carcinoma. A small number of patients were treated, but of note, the drug demonstrated very clear activity. In fact, of 8 patients with multiple tumors that could be looked at, 4 achieved a partial response.
This is a very interesting report. Obviously, there needs to be more data looking at the use of this particular agent in basal cell carcinoma. But it raises the very important question and issue of whether we will be able to find drugs that we have not considered as anticancer agents that might affect a particular target and, in fact, might be quite relevant anticancer agents in those settings.
One of the particular advances that might occur with this is that some of these agents may have very different kinds of toxicities than we traditionally think of with our anticancer agents. In fact, these might be drugs that are widely used in other conditions very safely. Therefore, it is possible that we might be able to find new anticancer agents among old drugs that we use for nonmalignant conditions.
I encourage you, if you're interested in this topic, to read this very interesting article (which appeared in the March 10, 2014, issue of the Journal of Clinical Oncology) titled "Open-Label, Exploratory Phase II Trial of Oral Itraconazole for the Treatment of Basal Cell Carcinoma."
I thank you for your attention.
Hello. I'm Dr. Maurie Markman, from the Cancer Treatment Centers of America in Philadelphia.
I want to discuss a very interesting question in the area of precision or genomic medicine in the cancer arena. This is sort of an interesting twist on the question of the use of anticancer agents that have not been approved by the US Food and Drug Administration (FDA) for a particular malignancy.
Usually, we're talking about a drug that might have been approved for the treatment of a particular condition -- but it's an anticancer agent. It might be used for breast cancer, and lo and behold, we find that there might be some activity (at least in theory) in lung cancer or perhaps in a hematologic malignancy because a particular molecular marker that is present in the tumor -- for example, HER2 overexpression -- might be present not only in breast cancer, but also in lung cancer or even lymphoma.
But what we're talking about is an anticancer agent approved for the use of treatment of a cancer and perhaps used in another malignancy.
The question to be asked in this brief discussion is this: What if one were to find a molecular marker that appears to be relevant in the treatment of cancer and, through preclinical evaluation, one finds that a drug that had been approved for an entirely different purpose -- having nothing whatsoever to do with the treatment of cancer -- also appeared to affect that particular molecular target? One might ask the question, is it possible that a drug that is given for a tumor type where there was a particular molecular abnormality, but is not currently used in the treatment of malignancy, might be effective in that situation?
We have a very interesting example, at least in a preliminary way, of where that might be quite relevant. It turns out that in the treatment of metastatic or advanced basal cell carcinoma, there is a molecular pathway known as the "hedgehog pathway" that appears to be quite relevant in the progression of that malignancy. In fact, there has recently been a drug approved specifically for the treatment of advanced metastatic basal cell carcinoma on the basis of the presence of that pathway.
It turns out that the antifungal agent itraconazole also affects the hedgehog pathway. In a very interesting article in the March 10, 2014, issue of the Journal of Clinical Oncology, investigators report on a phase 2 trial of the use of oral itraconazole in the treatment of basal cell carcinoma. A small number of patients were treated, but of note, the drug demonstrated very clear activity. In fact, of 8 patients with multiple tumors that could be looked at, 4 achieved a partial response.
This is a very interesting report. Obviously, there needs to be more data looking at the use of this particular agent in basal cell carcinoma. But it raises the very important question and issue of whether we will be able to find drugs that we have not considered as anticancer agents that might affect a particular target and, in fact, might be quite relevant anticancer agents in those settings.
One of the particular advances that might occur with this is that some of these agents may have very different kinds of toxicities than we traditionally think of with our anticancer agents. In fact, these might be drugs that are widely used in other conditions very safely. Therefore, it is possible that we might be able to find new anticancer agents among old drugs that we use for nonmalignant conditions.
I encourage you, if you're interested in this topic, to read this very interesting article (which appeared in the March 10, 2014, issue of the Journal of Clinical Oncology) titled "Open-Label, Exploratory Phase II Trial of Oral Itraconazole for the Treatment of Basal Cell Carcinoma."
I thank you for your attention.
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