Malignant tumors have a unique microbiome that can alter their survival time and response to treatment, regardless of the organs in which they develop. The intestinal microbiome can indirectly affect the tumor response, through systemic mechanisms, but the mechanism by which the bacteria developed at the level of tumor cells can directly impact their growth, survival and function has not yet been discovered.
Researchers at The University of Texas MD Anderson Cancer Center showed, in a study published in Cancer Cell, that intratumoral lactic acid-producing bacteria can lead to resistance to radiotherapy. These results may lead to the development of new targeted cancer therapies directed against these bacterial species.
Lactobacillus iners is one of the bacteria that causes cancer cells to become resistant to radiation therapy by reprogramming metabolic signaling pathways, being also associated with a poorer prognosis especially in cervical cancer. About 40% of L-lactate producing bacterial species similar from the point of view of the genome to L. Iners, commensals in other organs, are also associated with significantly impaired survival in colorectal, lung, head and neck and skin cancers. These findings demonstrate that lactic acid-producing bacteria at the tumor level can alter cellular metabolism and lactic acid signaling pathways, leading to the development of resistance to therapy.
Image by Freepik
L. iners is part of a group of fermentation bacteria that produce lactic acid. The L-lactate produced replaces the use of glucose in metabolic cycles and in combating the oxidative stress that occurs after radiation therapy. Tumor-level expression of lactic acid and lactate dehydrogenase is already associated with more aggressive cancer cell growth and poor prognosis in many cancers.
“These lactic acid-producing bacteria are apparently responsible for changing signaling pathways by causing cancer cells to use lactate instead of glucose to fuel growth and proliferation from oxidative stress following radiation therapy. This is a potential paradigm shift and we are currently working on new approaches to target these specific intratumoral bacteria. We hope these efforts will lead to strategies that can benefit patients with various oncological pathologies,” said Lauren Colbert, MD, co-author, assistant professor, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston , in one article published in Medical News.
They found that there is a link between the development of resistance to radiation therapy and the lactic acid-producing bacteria L. iners, with increased recurrences and decreased survival in patients diagnosed with cervical cancer. This finding is not limited to bacteria in cervical tumors, but exophytic tumors at this level facilitated repeated sampling of cells for tumor microbiome testing. The study included 101 patients diagnosed with cervical cancer, between 2015 and 2022, during which they received chemotherapy along with radiotherapy.
The researchers were able to induce resistance to the treatment by introducing in vitro the bacteria L. ines into the cancer cells, altering their metabolism by increasing the use of lactic acid. These results led to the conclusion that the bacteria have functions inside tumor cells that do not exist in healthy patients, suggesting that there may be changes at the bacterial level before cancer develops.
Read also:
2023-12-04 15:22:15
#STUDY #Resistance #radiotherapy #influenced #lactic #acidproducing #bacteria #tumor #level #therapeutic #implications #duty #report
