Fusobacterium nucleatum levels in tumors may predict poorer responses to chemotherapy and act as a marker for poor prognosis in esophageal cancer. Could this lead to new antibiotic therapies targeting this bacterial species?
As the sixth leading cause of cancer death, esophageal cancer remains highly lethal, with five-year survival rates of 15%-20%. Esophageal squamous cell cancer (ESCC) is the most common subtype of the disease. Current treatments include (sidenote:
Neoadjuvant chemotherapy
To reduce tumor size prior to surgery
) (NAC) followed by esophageal resection. Although patients who respond favorably to NAC have a better chance of survival, most tumors develop NAC resistance. Understanding the mechanisms behind NAC resistance is therefore key to improving treatment response and, accordingly, patient survival.
What role does Fusobacterium nucleatum play in tumors?
The composition of the gut microbiota has already been shown to influence responses to certain cancer treatments such as immunotherapy and chemotherapy. In addition, intratumoral Fusobacterium nucleatum levels have recently been shown to be associated with reduced survival and/or increased recurrence rates in colorectal cancer and in ESCC. This encouraged researchers to assess, for the first time, the prognostic value of intratumoral F. nucleatum levels in ESCC patients and their ability to predict NAC response. The study was carried out in 551 Japanese subjects from two independent cohorts.
Predictive marker of reduced survival rate...
First finding: tumor tissue has higher levels of F. nucleatum compared to adjacent healthy tissue. In addition, intratumoral F. nucleatum levels are associated with both the stage of tumor progression and a reduction in relapse-free survival (RFS). The link between F. nucleatum and reduced survival is observed even in early-stage patients, suggesting that this bacterial species may promote tumor aggressiveness. Intratumoral F. nucleatum levels may therefore serve as a prognostic biomarker.
... and poor responses to chemotherapy
Lastly, analyses in a subgroup of 101 patients receiving NAC showed that patients with increased levels of F. nucleatum had a lower response to tumor treatment. Although the mechanisms likely to explain the role of F. nucleatum in increased tumor resistance remain speculative (activation of metabolic pathways leading to cell autophagy?; deactivation of chemotherapeutic substances?), the researchers point out a promising therapeutic avenue: improving responses to chemotherapy via an antibiotic therapy targeting F. nucleatum. More work to follow.
