Bacterial DnaK reduces the activity of anti-cancer drugs cisplatin and 5FU.
J Transl Med
; 22(1): 269, 2024 03 12.
Article
in En
| MEDLINE
| ID: mdl-38475767
ABSTRACT
BACKGROUND:
Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by cancer-associated bacteria (CAB) that impair tumor suppressor functions. Our previous research found that Mycoplasma fermentans DnaK, a chaperone protein, impairs p53 activities, which are essential for most anti-cancer chemotherapeutic responses.METHODS:
To investigate the role of DnaK in chemotherapy, we treated cancer cell lines with M. fermentans DnaK and then with commonly used p53-dependent anti-cancer drugs (cisplatin and 5FU). We evaluated the cells' survival in the presence or absence of a DnaK-binding peptide (ARV-1502). We also validated our findings using primary tumor cells from a novel DnaK knock-in mouse model. To provide a broader context for the clinical significance of these findings, we investigated human primary cancer sequencing datasets from The Cancer Genome Atlas (TCGA). We identified F. nucleatum as a CAB carrying DnaK with an amino acid composition highly similar to M. fermentans DnaK. Therefore, we investigated the effect of F. nucleatum DnaK on the anti-cancer activity of cisplatin and 5FU.RESULTS:
Our results show that both M. fermentans and F. nucleatum DnaKs reduce the effectiveness of cisplatin and 5FU. However, the use of ARV-1502 effectively restored the drugs' anti-cancer efficacy.CONCLUSIONS:
Our findings offer a practical framework for designing and implementing novel personalized anti-cancer strategies by targeting specific bacterial DnaKs in patients with poor response to chemotherapy, underscoring the potential for microbiome-based personalized cancer therapies.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplasms
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
J Transl Med
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos