One of the most fascinating areas of modern oncology is drug repurposing: the study of drugs that are already known and used to treat other diseases but may have additional effects that are potentially useful against cancer.<\/p>\n\n\n\n
If you\u2019re interested in the latest developments in cancer treatment, you should check out the Care Oncology Protocol (COC), an adjuvant metabolic therapy protocol developed by clinical oncologists and researchers in the United Kingdom, based precisely on this concept of drug repurposing, using medications such as metformin, atorvastatin, doxycycline, and mebendazole.<\/p>\n\n\n\n
But, after all\u2026 why would an antibiotic spark interest in cancer research?<\/p>\n\n\n\n
Doxycycline has been studied because it has a mechanism of action that is quite different from that of most conventional treatments. While traditional chemotherapy primarily seeks to eliminate tumor cells that undergo rapid cell division (which make up most of the tumor mass), studies suggest that doxycycline may interfere with the metabolism of a subpopulation of cells known as cancer stem cells (CSCs).<\/p>\n\n\n\n
These cells account for only a small fraction of the tumor, but are considered by many researchers to be one of the main mechanisms involved in treatment resistance, disease recurrence, and the development of metastases. Because they often remain in a state of slow division, they can survive chemotherapy and radiation therapy and subsequently give rise to tumor growth once again.<\/p>\n\n\n\n
In other words, they would act as true \u201cseeds\u201d of cancer. The Achilles\u2019 heel of tumor stem cells: the mitochondria<\/p>\n\n\n\n
To understand this hypothesis, we need to turn to evolutionary biology.<\/p>\n\n\n\n
Several studies suggest that many tumor stem cells are highly dependent on oxidative phosphorylation (OXPHOS) and mitochondrial function to maintain their ability to survive, self-renew, and resist treatment.<\/p>\n\n\n\n
That is precisely where doxycycline stands out.<\/p>\n\n\n\n
According to the endosymbiotic theory, which is accepted by modern biology, millions of years ago, mitochondria were independent bacteria that came to live inside the ancestral cells that gave rise to complex organisms.<\/p>\n\n\n\n
Because of this evolutionary origin, mitochondrial ribosomes bear a strong structural resemblance to bacterial ribosomes\u2014which are precisely the classic target of doxycycline.<\/p>\n\n\n\n
How might doxycycline affect cancers?<\/p>\n\n\n\n
When used in this experimental context, the hypothesis is that doxycycline exerts an effect on mitochondria similar to the one it exerts on bacteria.<\/p>\n\n\n\n
1\ufe0f\u20e3 Inhibition of mitochondrial biogenesis: Doxycycline can bind to mitochondrial ribosomes, reducing the production of proteins essential for normal mitochondrial function.<\/p>\n\n\n\n
2\ufe0f\u20e3 Reduced ATP production: Without these proteins, oxidative phosphorylation (OXPHOS) is impaired, reducing the production of ATP, the cell\u2019s primary energy currency.<\/p>\n\n\n\n
3\ufe0f\u20e3 Loss of metabolic advantage: Several studies suggest that many tumor stem cells exhibit less metabolic flexibility than other tumor cells and rely heavily on mitochondrial activity.<\/p>\n\n\n\n
Thus, by impairing the function of these organelles, these cells may lose some of their ability to survive stress, resist treatment, migrate, and give rise to new tumors.<\/p>\n\n\n\n
What do the studies show so far?<\/p>\n\n\n\n
Much of the evidence supporting this mechanism comes from laboratory (in vitro) studies, animal models, and some early clinical studies.<\/p>\n\n\n\n
Many researchers consider the results to be quite interesting, especially since doxycycline is a well-known, relatively inexpensive drug with a well-established safety profile when used for its traditional indications.<\/p>\n\n\n\n
However, larger and more robust clinical studies are still needed to determine with greater certainty:<\/p>\n\n\n\n
\u2022 which patients might benefit;
\u2022 in which types of cancer;
\u2022 what the ideal doses and duration of treatment would be;
\u2022 which treatment combinations would be most effective;
\u2022 and what the actual impact would be on key outcomes, such as reduced recurrence, metastasis, quality of life, and survival.<\/p>\n\n\n\n
Although the biochemical mechanisms described are quite plausible and biologically interesting, this does not mean that their clinical efficacy has already been proven.<\/p>\n\n\n\n
That is precisely why this strategy continues to be the subject of intensive research in metabolic oncology.<\/p>\n\n\n\n
\u26a0\ufe0f IMPORTANT<\/strong><\/p>\n\n\n\n Doxycycline is not part of the standard treatment for most cancers.<\/p>\n\n\n\n Its use for this purpose remains experimental and\/or adjunctive in specific contexts and should always be evaluated on a case-by-case basis by the responsible medical team.<\/p>\n\n\n\n The purpose of this post is purely educational, showing how older drugs can reveal surprising mechanisms and open up new possibilities for future therapeutic strategies.<\/p>\n\n\n\n This is exactly how science advances: by investigating biologically plausible hypotheses, confirming those that actually work, and discarding those that show no clinical benefit.<\/p>","protected":false},"excerpt":{"rendered":" Uma das \u00e1reas mais fascinantes da oncologia atual \u00e9 o reposicionamento de medicamentos (drug repurposing): o estudo de f\u00e1rmacos j\u00e1 conhecidos e utilizados para outras doen\u00e7as que podem apresentar efeitos adicionais potencialmente \u00fateis contra o c\u00e2ncer. Se voc\u00ea se interessa por atualidades na abordagem do C\u00e2ncer, vale a pena conhecer o Care Oncology Protocol (COC), […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-25452","post","type-post","status-publish","format-standard","hentry","category-blog"],"acf":[],"_links":{"self":[{"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/posts\/25452","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/comments?post=25452"}],"version-history":[{"count":2,"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/posts\/25452\/revisions"}],"predecessor-version":[{"id":25454,"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/posts\/25452\/revisions\/25454"}],"wp:attachment":[{"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/media?parent=25452"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/categories?post=25452"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/icaro.med.br\/en\/wp-json\/wp\/v2\/tags?post=25452"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}