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04/02/2019

Antibiotics can become a new weapon against cancer by decreasing tumor growth

AntibioticsCancer_(884-504)

04/02/2019

Researchers from VHIR have shown for the first time in vivo that bactericidal antibiotics in combination with autophagy blockers decrease tumor growth.

The main obstacle to the cure of cancer is the appearance of metastasis and the acquisition of resistance to treatments. In this context, the group of Biomedical Research in Stem Cells of Cancer of the Vall d'Hebron Research Institute (VHIR), led by Dr. Matilde E. Lleonart, has shown for the first time in vivo that bactericidal antibiotics in combination with Blockers of autophagy decrease tumor growth. They have achieved it in an animal model of triple negative breast cancer. The results of this promising study have been published in the journal https://www.mcponline.org/content/early/2018/10/29/mcp.RA118.001102 Molecular & Cellular Proteomics.Cancer stem cells (CSCs) are the cell population responsible for the growth of the tumor, they are attributed a greater resistance to current treatments and are also involved in the appearance of metastases. Next to them are the resistant cells, those that have developed a certain degree of immunity to the treatments, which is why they are responsible for the maintenance and dissemination of the tumor.With the idea of discovering the proteins involved in the acquisition of this resistance, the researchers carried out a proteomic and metabolomic analysis of cells generated in the laboratory that were induced to be resistant to cyclophosphamide, cisplatin and doxorubicin, the main drugs against breast cancer. Triple-Negative particularly aggressive and designated as TNBC. "We wanted to check whether the resistant or chemoresistant cells had similarities with the CSCs in terms of phenotype and also to check whether the two populations are dependent on the mitochondria, as the latest hypotheses suggest," explains Dr. Matilde E. Lleonart, chief of the Biomedical Research Group in Cancer Stem Cells of the VHIR. This research group discovered that both populations (resistant cells and CSCs) share many characteristics and molecular routes, and also that many of these pathways are related to the mitochondria.Once confirmed that CSCs and chemoresistant cells derived from triple-negative breast cancer cells would depend on mitochondria to survive, an antibiotic was selected to continue the study: linezolid, for its ability to induce mitochondrial dysfunction.The researchers, led by Dr. Lleonart and Dr. Alex Lyakhovich of the same VHIR research group, were able to provide the first in vivo evidence that linezolid suppresses the rate of tumor growth and that it is accompanied by an increased autophagy (regenerative process that controls cell survival and, in the case of cancer, promotes its growth and metastasis).In this sense, and guided by a previous work of the group that suggested that the simultaneous treatment with specific antibiotics and autophagy blockers could have a great therapeutic value, they demonstrated that the bactericidal antibiotics used in combination with autophagy blockers diminish the growth of the tumor."This study places mitochondria at the centre of attention of cancer therapy and antibiotics as effective agents to eliminate CSCs and resistant cells," says Dr. Lleonart, Therefore, researchers propose the combined administration of an antibiotic and an inhibitor of autophagy to stop tumor growth and eliminate the specific population of resistant cells.Eliminating this population that until now escapes the treatments that exist is very important both from the clinical point of view and the progression of the disease. And to be able to do it using already commercialized antibiotics whose dosage, toxicity, etc. are known. opens the door to the repositioning of drugs in the treatment of cancer.This study has received funding from the Ministry of Health through the Carlos III Health Institute and the support of the Foundation of the Spanish Association Against Cancer.

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