That's how chemo damages the heart

Published on Wednesday, 30 January 2013

Doxorubicin and cardiotoxicityIt has been identified a molecular mechanism that explains why a chemotherapy drug can cause heart problems. It's doxorubicin, in use since 50 years to combat many types of cancer.

Scientists from the University of Texas (MD Anderson Cancer Center) have discovered an unexpected molecular mechanism that through the enzyme Top2b, brings the molecule to attack the heart muscle.

The research should help identify those patients most at risk and those who can tolerate safely the doxorubicin. The study is published in the journal Nature Medicine. The doxorubicin binds to the enzyme Top2, which controls the "unwinding" of DNA necessary for cell division.





Identification of the molecular basis of doxorubicin-induced cardiotoxicity



Doxorubicin is believed to cause dose-dependent cardiotoxicity through redox cycling and the generation of reactive oxygen species (ROS). Here we show that cardiomyocyte-specific deletion of Top2b (encoding topoisomerase-IIβ) protects cardiomyocytes from doxorubicin-induced DNA double-strand breaks and transcriptome changes that are responsible for defective mitochondrial biogenesis and ROS formation. Furthermore, cardiomyocyte-specific deletion of Top2b protects mice from the development of doxorubicin-induced progressive heart failure, suggesting that doxorubicin-induced cardiotoxicity is mediated by topoisomerase-IIβ in cardiomyocytes.


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The type Top2b is practically absent in cancer cells but is present in the normal ones: doxorubicin binds to Top2b in cardiomyocytes, the cells of the heart, causing an increase in oxidative stress which damages the heart muscle tissues.

Hey, the research advances even if we (patients) don't realize it.  The Doxorubicin is used since fifty years, is the one that colors in red the drip: I had it done ​​in 2008 and the lady who was with me at the Hospital Buzzi, in 1984, had ​​her too. The same. Around the world, for half a century, every woman who has breast cancer is treated like this. Then, today, if its breast cancer has a characteristic, receives a monoclonal antibody (only one) suitable to restrain a   growth factor of his tumor (only one).Obviously (even if the drug is organic) after receiving a good dose of chemo, just to destroy all that is bio...!

At least let's not call it targeted therapy or customized, let's use the right words, as in crossword puzzles: standardized therapy. I forgot: the same is also used for the leukemias, lymphomas, tumors of the lung, stomach, thyroid, ovary, bladder, for sarcomas, bone tumors, neuroblastoma, soft tissue tumor.

Is there anyone who remembers the trial of doxorubicin? Those who have information, write to me. I would be interested to know if, for ethical reasons, it was tested only on patients at the fourth stage or terminal. And how many survived the experiment!




 Supplementary Figures 1–5 and Supplementary Tables 1 and 2



Translated by: Alina Mina Leonard

Read here the original article (Italian language) by journalist Gioia Locati.