How Intratumoral Microbiota is Revolutionizing Cancer Therapy
For decades, the conventional scientific wisdom held that tumors were largely sterile environments, isolated from the microbial world that inhabits other parts of our bodies. This view has been radically overturned.
According to the World Cancer Report 2022, there were approximately 20 million new cancer cases and 9.7 million cancer-related deaths worldwide in 2022 1 .
Microbes like polyketide synthase-positive E. coli trigger genetic mutations, while Fusobacterium nucleatum promotes DNA double-strand breaks 2 .
Intratumoral microbes alter local metabolism in ways that support tumor growth, generating metabolites that promote angiogenesis 7 .
| Mechanism | Example Microbes | Effect on Cancer |
|---|---|---|
| Genetic Instability | Polyketide synthase+ E. coli, Fusobacterium nucleatum | DNA damage, impaired repair, mutations |
| Epigenetic Modifications | Bacteroides fragilis | Altered gene expression, signaling pathway changes |
| Immune Evasion | HPV, HBV | Suppressed immune detection, reduced inflammation |
| Oncogenic Pathway Activation | Fusobacterium nucleatum | Enhanced survival, therapy resistance |
| Metabolic Reprogramming | Various bacterial communities | Changed tumor microenvironment, nutrient availability |
In 2020, a landmark study led by Nejman et al. dramatically advanced our understanding of intratumoral microbiota by comprehensively investigating bacteria in human tumors 9 . This research examined 1,010 tumor samples across seven cancer types.
Samples: 1,010 tumor samples
Cancer Types: 7 different types
Key Finding: Each cancer type has distinct microbial composition
Impact: Linked bacterial presence with clinical outcomes
| Cancer Type | Predominant Microbiota | Unique Characteristics |
|---|---|---|
| Breast Cancer | Firmicutes, Proteobacteria, Actinobacteria | Most rich and diverse microbiome |
| Colorectal Cancer | Bacteroidetes, Firmicutes, Fusobacterium | Associated with KRAS mutation and microsatellite instability |
| Pancreatic Cancer | Proteobacteria, Malassezia fungi | Dominated by Proteobacteria |
| Lung Cancer | Corynebacterium, K. pneumoniae, Thermus | Specific environmental bacteria |
Primary Function: Bacterial identification and classification
Advantages: Comprehensive profiling, cost-effective
Limitations: Doesn't capture viruses or fungi well
Primary Function: Visualize bacteria within tissue
Advantages: Confirms intracellular location, spatial context
Limitations: Limited resolution, requires specific probes
Primary Function: Grow intratumoral microbes in lab
Advantages: Enables functional studies of live microbes
Limitations: Most microbes remain unculturable
Primary Function: Map microbial location and activity
Advantages: Simultaneously profiles microbes and host response
Limitations: Emerging technology, not widely available
Modified bacteria can be designed to selectively target tumors and deliver therapeutic payloads 6 .
The discovery of intratumoral microbiota has fundamentally transformed our understanding of cancer biology, revealing tumors as complex ecosystems where human and microbial cells interact.