22 Jul Melanoma: Animal Model Suggests Antibiotics May One Day Be Helpful in Controlling Resistant Disease
MedicalResearch.com Interview with:
Eleonora Leucci, Ph.D Assistant Professor
Laboratory for RNA Cancer Biology
Department of Oncology
MedicalResearch.com: What is the background for this study?
Response: Back in 2016, while I was characterising the RNA SAMMSON as essential for mitochondrial translation in melanoma, I noticed that its inhibition was causing cell death across a large spectrum of melanoma cell lines and models, irrespectively of their genetic background and cell state. At that time I still did not know why the effect was so pronounced on melanoma cells, but I knew that antibiotics of the tetracycline family could also block mitochondrial translation and I thought about repurposing them to treat melanoma.
MedicalResearch.com: What are the main findings?
Response: -We are now able to show that all the models derived from therapy-resistant melanoma cells showed activation of a pathway called the Integrated stress response.
- This response was believed to help the cancer cells to survive the treatment by slowing down their translation, the most energy consuming process in the cell, thus making them quiescent. It is well know that the cytosolic and mitochondrial translational machineries are balanced to ensure the proper functioning of the mitochondria. However, here we showed that despite switching off protein synthesis in the cytosol, this pathway ensures that mitochondrial translation is on at all time.
- This creates a vulnerability towards agents blocking mitochondrial translation such as some categories of antibiotics.
- Antibiotics are able to significantly delay and in some case prevent relapse in response to targeted therapy and delay progression in models intrinsically resistant to immune therapy.
MedicalResearch.com: What should readers take away from your report? Could doxycycline potentially be used against other forms of cancer?
Response: Tetracyclines may may offer an opportunity for the treatment of melanoma patients otherwise resistant to therapy. Additionally, considering that the exponential growth in health care costs is an issue of great concern for many countries, the use of antibiotics readily available and cheap would ensure an easy access to the treatment for all patients, which is certainly not the case with the current standard of care for this disease around the world.
Antibiotics have been shown to be effective also in other cancer types such as AML and double hit lymphoma, so there is the possibility to extend their use to other systems. However, whether this will improve or worsen the outcome of the therapies in use is not necessarily known.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: I would definitely discourage patients to take antibiotics without the supervision of their treating physician, since it is well known that some antibiotics (belonging to a different pharmacological category) can actually interfere with their treatment.
MedicalResearch.com: Is there anything else you would like to add?
Response: I would like to thank all the patients and families and all the funding bodies for their trust and support. Without them our work would have never been possible.
Roberto Vendramin, Vicky Katopodi, Sonia Cinque, Angelina Konnova, Zorica Knezevic, Sara Adnane, Yvessa Verheyden, Panagiotis Karras, Ewout Demesmaeker, Francesca M. Bosisio, Lukas Kucera, Jan Rozman, Ivan Gladwyn-Ng, Lara Rizzotto, Erik Dassi, Stefania Millevoi, Oliver Bechter, Jean-Christophe Marine, Eleonora Leucci; Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma. J Exp Med 6 September 2021; 218 (9): e20210571. doi: https://doi.org/10.1084/jem.20210571
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