The metallodrug: could this be the next antitumor drug?

The metallodrug: could this be the next antitumor drug?
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Some types of cancer cannot be treated with classic chemotherapy, so a team of scientists are working on a metallodrug, which has the potential to be the next antitumor drug.

Published in Angewandte Chemie, Inserm, CNRS, Sorbonne University, PSL university, University Grenoble Alpes and the European Synchrotron (ESRF), are all working on the next antitumor drug, using a metallorganic molecule. Their research has given thorough insights into its mechanism in attacking cancer cells.

It’s about time we develop an antitumor drug

Triple-negative breast cancer, which represents 10-20% of breast cancers, is not fuelled by hormones. In fact, it tests negative for oestrogen and progesterone receptors and excess HER2 protein. This essentially means that it does not respond to hormonal therapy and antibody medicines.

Because this is more aggressive and often has a higher grade than other types of breast cancer, the scientific community is persistent in finding a treatment.

The diverse team of scientists have joined forces to study the path that metallorganic molecules or metallocifens, derivatives of the widely-used drug tamoxifen, follow to reach cancerous cells.

These metallodrugs were developed by Professor G. Jaouen and his group at Sorbonne University and PSL University, France, and have demonstrated a broad spectrum of efficacy and potential to significantly overcome drug resistance.

Can the metallodrug work?

Sylvain Bohic, scientist at the Inserm and main author of the study, explains: “We know this molecule works because extensive tests have been already carried out, but we don’t know how it manages to kill the cancer cell. That is why we want to quantify and localise the drug inside the cell, to understand its efficiency”

The scientists used the beamline ID16A at the ESRF for their investigations. State-of-the-art synchrotron imaging brought unique insight into the intracellular distribution of the metallocifen, which they could track down with a resolution of 35 nanometres.

“The investigations are going on for a few years and finally benefit of the latest capabilities of the instrument in terms of 2D and 3D cryo X-ray fluorescence approaches.” Adds Peter Cloetens, in charge of ID16A.

For the first time, they showed how the molecule penetrates the membrane of the cancerous cell in an extremely easy manner, due to its lipophilic nature and target an essential cellular organelle the endoplasmic reticulum a large organelle made of membranous sheets and tubules that begin near the nucleus and extend across the cell.

Then, it oxidises and attacks different parts of the cell at the same time, leading to efficient anticancer activity.

Bohic explains further: “Think of it as if the metallorganic molecule starts many fires in different places in the cancer cell, until the tumoral cell can’t deal with it anymore and it dies.”

Promising results

“This study is a contribution to the understanding of alternative mechanisms from chemotherapy to heal cancer. We are at an early stage of research, so clinical trials have not begun yet, but so far it is promising.” concludes Jaouen.

The results are promising as this new family of metallodrugs, which acts on multiple targets, could one day become an alternative to chemotherapy and help to overcome drug resistance while holding down costs.

The next step is to find out how this molecule acts in healthy cells and to study toxicology.


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