An emerging understanding of the Janus face of the human microbiome: enhancement versus impairment of cancer therapy

摘要

Sir, Commensal bacteria have been shown to modulate myeloid-derived cell functions in the tumour microenvironment that are crucial for an optimal response to immunotherapy or platinum-based chemotherapy. Also, the therapeutic efficacy of cyclo-phosphamide has been proven to be mediated by selected species of Gram-positive bacteria that stimulate a specific anticancer immune response. As a result, a decreased efficiency of cancer therapy was reported in germ-free or antibiotic-treated mice. These results underscore the potential risks of manipulating the microbiome prior to or during cancer treatment. Here, we want to place these findings in a broader perspective by also taking into account the, often opposite, effects microbiota might have on the anticancer activity of nucleoside-based antimetabol-ite drugs. Nucleoside analogues (NAs) represent ~20% of the approved anticancer drugs and have become cornerstones of successful treatment for cancer patients.3 The clinical use of several potent NAs (e.g. floxuridine and trifluridine) has been limited due to drug inactivation by catabolic enzymes such as nucleoside phosphory-lases (NPs), which can be expressed both by mammalian cells and by commensal prokaryotes. Their therapeutic potential may therefore be improved by coadministration of a specific NP inhibitor. Indeed, TAS-102, a combination of trifluridine with the highly potent and specific thymidine phosphorylase (TP) inhibitor TPI, is currently being evaluated in a Phase III clinical trial to treat meta-static colorectal cancer.