- Jul 2018
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europepmc.org europepmc.org
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On 2014 Aug 12, Miguel Lopez-Lazaro commented:
Most of the patients with advanced cancers die because the drugs used in their treatment have a low ability to kill their cancer cells at concentrations that do not significantly affect their normal cells. Although these patients need drugs that kill their cancer cells selectively, we typically look for drugs that kill cancer cells at low concentrations or that have specific mechanisms of action. These strategies do not reliably predict the ability of a drug to kill cancer cells selectively and many times result in the selection of compounds with low therapeutic potential and in the failure to detect compounds with therapeutic potential.
In vitro therapeutic potential can be easily and efficiently assessed answering the following question:
Can my drugs improve the ability of the standard drugs to kill cancer cells without significantly affecting nonmalignant cells from a variety of appropriate tissues? (1)
In this article, the authors demonstrate that organoiridium complexes improve the ability of platinum complexes to kill cancer cells at low concentrations. They also show that their cytotoxic activity is mediated by a pro-oxidant mechanism of action. One of their complexes could also match the selectivity of cisplatin when tested in ovarian cancer cells versus lung nonmalignant cells.
In my opinion, additional nonmalignant cell lines (or primary cells) from appropriate tissues should be used to assess the therapeutic potential of these compounds further. If one only uses one cancer cell line and one non-malignant cell line originated from different tissues, the observed selective anticancer effect could be caused by tissue differences in sensitivity. In addition, cells from other tissues commonly affected by chemotherapy could be highly sensitive to the cytotoxic activity of organoiridium complexes. In view of the possible relevance of the results presented by the authors, I think that these additional experiments are worth considering.
Dr. Lopez-Lazaro
(1) Lopez-Lazaro, M. Experimental Cancer Pharmacology for Researchers: At What Concentration Should my Drug Kill Cancer Cells so that it has Potential for Cancer Therapy? 2014, ASIN: B00MMO25NM http://www.amazon.com/Experimental-Cancer-Pharmacology-Researchers-Concentration-ebook/dp/B00MMO25NM/ref=sr_1_1?ie=UTF8&qid=1407829198&sr=8-1&keywords="at+what+concentrations+should"
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
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- Feb 2018
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europepmc.org europepmc.org
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On 2014 Aug 12, Miguel Lopez-Lazaro commented:
Most of the patients with advanced cancers die because the drugs used in their treatment have a low ability to kill their cancer cells at concentrations that do not significantly affect their normal cells. Although these patients need drugs that kill their cancer cells selectively, we typically look for drugs that kill cancer cells at low concentrations or that have specific mechanisms of action. These strategies do not reliably predict the ability of a drug to kill cancer cells selectively and many times result in the selection of compounds with low therapeutic potential and in the failure to detect compounds with therapeutic potential.
In vitro therapeutic potential can be easily and efficiently assessed answering the following question:
Can my drugs improve the ability of the standard drugs to kill cancer cells without significantly affecting nonmalignant cells from a variety of appropriate tissues? (1)
In this article, the authors demonstrate that organoiridium complexes improve the ability of platinum complexes to kill cancer cells at low concentrations. They also show that their cytotoxic activity is mediated by a pro-oxidant mechanism of action. One of their complexes could also match the selectivity of cisplatin when tested in ovarian cancer cells versus lung nonmalignant cells.
In my opinion, additional nonmalignant cell lines (or primary cells) from appropriate tissues should be used to assess the therapeutic potential of these compounds further. If one only uses one cancer cell line and one non-malignant cell line originated from different tissues, the observed selective anticancer effect could be caused by tissue differences in sensitivity. In addition, cells from other tissues commonly affected by chemotherapy could be highly sensitive to the cytotoxic activity of organoiridium complexes. In view of the possible relevance of the results presented by the authors, I think that these additional experiments are worth considering.
Dr. Lopez-Lazaro
(1) Lopez-Lazaro, M. Experimental Cancer Pharmacology for Researchers: At What Concentration Should my Drug Kill Cancer Cells so that it has Potential for Cancer Therapy? 2014, ASIN: B00MMO25NM http://www.amazon.com/Experimental-Cancer-Pharmacology-Researchers-Concentration-ebook/dp/B00MMO25NM/ref=sr_1_1?ie=UTF8&qid=1407829198&sr=8-1&keywords="at+what+concentrations+should"
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
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