Tetracycline Family Antibiotics May Help Fight Melanoma by Targeting Cancer Cell Mitochondria

Antibiotics of the tetracycline family can help treat certain forms of skin cancer, specifically by targeting the mitochondria, or energy centers, of cancer cells, according to a team of dermatologists from the Catholic University of Leuven. Indeed, some antibiotics appear to be specifically effective against melanoma, according to this preclinical study published in the Journal of Experimental Medicine (JEM).

Melanoma

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Belgian scientists may have found a new weapon in the fight against melanoma: antibiotics that target the “powerhouses” of cancer cells. These antibiotics take advantage of the vulnerability that occurs in tumor cells as they try to survive cancer treatment. Preventing melanoma cells from surviving and escaping.

“As cancer progresses, some melanoma cells may escape the treatment and ‘hide’ from the immune system, giving them the chance to form a new tumor mass later,” explained lead author Eleonora Leucci, a cancer researcher and RNA biologist at KU Leuven. “However, to survive cancer treatment, these inactive cells must maintain their mini-electrochemical stations or mitochondria. Because mitochondria descend from bacteria that have started living in the cells over time, they are very sensitive to certain classes of antibiotics.

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The team is testing the concept of targeting the mitochondria of cancer cells with antibiotics, in this case in mouse models of melanoma. In practice, the researchers implanted patient-derived tumors into mice, which were then treated with antibiotics, either as a separate treatment or in combination with existing anti-melanoma therapies. The trial showed that:

• Antibiotics kill many cancer cells quickly and save precious time needed to activate immunotherapy
• For tumors that no longer respond to targeted therapies, antibiotics can extend life and in some cases even cure mice.
• Highly specific antibiotics: these antibiotics are currently rarely used to treat bacterial infections, mainly because of the increase in resistance. However, in this study, this resistance does not affect the effectiveness of the treatment, since the cancer cells are still very sensitive to these antibiotics.

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The researchers warn that melanoma patients should not try this treatment, which has not yet been validated in clinical trials. However, targeting mitochondria in melanoma cells already appears to be a promising option to complement standard cancer treatment.

NB. The best way to prevent melanoma from occurring in the first place is to avoid sun exposure and to keep track of any suspicious lesions on the skin. In most cases when melanoma is detected early a complete cure could be achieved. However, if the melanoma has already metastasized then a cure becomes difficult to achieve.

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FAQ: Tetracycline Antibiotics and Melanoma Treatment

1. How do tetracycline antibiotics help treat melanoma?
   These antibiotics target the mitochondria of melanoma cells, disrupting their energy production and making them more vulnerable to cancer treatments.
2. Why do mitochondria in melanoma cells respond to antibiotics?
   Mitochondria evolved from bacteria, making them sensitive to certain antibiotics. This vulnerability allows tetracycline antibiotics to weaken cancer cells.
3. Are these antibiotics already used for treating melanoma?
   No, this treatment is still in the preclinical stage and has not been validated for human use in clinical trials.
4. Can melanoma patients take these antibiotics now?
   No, melanoma patients should not try this on their own. The treatment is still experimental and requires further research before being considered safe or effective.
5. What were the key findings of the study?
   The study showed that antibiotics can rapidly kill cancer cells, extend survival in cases where standard treatments fail, and, in some cases, even cure mice of melanoma.
6. Do bacteria develop resistance to these antibiotics?
   Yes, but bacterial resistance does not affect their ability to kill melanoma cells, as cancer cells remain highly sensitive to them.
7. How were the antibiotics tested?
   Researchers implanted human-derived melanoma tumors into mice and treated them with antibiotics alone or in combination with existing melanoma therapies.
8. Can antibiotics replace current melanoma treatments?
   No, but they may become a complementary option to enhance existing therapies, particularly for tumors that stop responding to conventional treatments.
9. What is the best way to prevent melanoma?
   Avoid excessive sun exposure, use sunscreen, and monitor skin lesions for suspicious changes. Early detection significantly improves treatment outcomes.

References

Vendramin, R., Katopodi, V., Cinque, S., Konnova, A., Knezevic, Z., Adnane, S., Verheyden, Y., Karras, P., Demesmaeker, E., Bosisio, F. M., Kucera, L., Rozman, J., Gladwyn-Ng, I., Rizzotto, L., Dassi, E., Millevoi, S., Bechter, O., Marine, J.-C., & Leucci, E. (2021). Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma. Journal of Experimental Medicine, 218(9), e20210571. https://doi.org/10.1084/jem.20210571