Bacteria in tumours could influence cancer treatment response
November 2022
Fred Hutchinson Cancer Center, Seattle, USA
Fusobacterium nucleatum (Fn) is a dominant bacterial species in colorectal cancer (CRC) tissue that is associated with cancer progression and poorer patient prognosis. Following a small-molecule inhibitor screen of 1,846 bioactive compounds against an Fn CRC isolate, the researchers found that 15% of inhibitors are antineoplastic agents. Validation of these findings reveals that 5-fluorouracil (5-FU), a first-line CRC chemotherapeutic, is a potent inhibitor of Fn CRC isolates. The researchers also show that CRC E. coli isolates can modify 5-FU and relieve 5-FU toxicity toward otherwise-sensitive Fn and human CRC epithelial cells. Lastly, they demonstrate that ex vivo patient CRC tumour microbiota undergo community disruption after 5-FU exposure and have the potential to deplete 5-FU levels, reducing local drug efficacy. Together, these observations argue for further investigation into the role of the CRC intratumoural microbiota in patient response to chemotherapy.
The cancer chemotherapeutic 5-fluorouracil is a potent Fusobacterium nucleatum inhibitor and its activity is modified by intratumoral microbiota
Susan Bullman, Christopher D. Johnston
Added on: 01-05-2023
[1] https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01496-6[2] https://www.drugtargetreview.com/news/106710/bacteria-in-a-tumours-microbiome-could-influence-how-cancer-responds-to-treatment/
