Defining Microbial Ecosystems in Bladder Cancer Patients

Posted June 8, 2022

Philip Abbosh, M.D., Ph.D., The Research Institute of Fox Chase Cancer Center

Dr. Philip Abbosh
Dr. Philip Abbosh

Bladder cancer is one of the most expensive cancers to treat and has an increased prevalence within the Veteran community due to increased carcinogen exposure and tobacco use as compared to civilians. The usual treatment strategy for patients with stage II and III bladder cancer is to undergo chemotherapy followed by bladder removal (radical cystectomy). This is an incredibly life-altering procedure that requires patients to use an alternate route of passing urine such as a urostomy bag (collects urine outside body) for the rest of their lives. At the time of bladder removal, 30%-40% of patients will no longer have an identifiable tumor in their bladders and experience a pathologic complete response (pCR). These patients are usually cured; however, the reason some tumors respond and others do not is not fully understood.

Within the research community, there is an increasing understanding in bacteria’s role in causing, preventing, and modifying cancer as a whole. The microbiome (the community of bacteria, fungi, and viruses) found in bladder cancer has not been fully described, so studying the bacteria in these tumors could help scientists and physicians understand of the role of bacteria in bladder cancer and then potentially modify them for therapy. Dr. Philip Abbosh is a urologic oncologist with special interest in bladder cancer and whose research is focused on why patients respond to chemotherapy. Preliminary studies from his lab show that there are several types of bacteria that are found in bladder tumors but are normally only seen in other organs, and have not been previously seen in the bladder or bladder cancer. Dr. Abbosh believes these bacteria might be increasing or decreasing the effectiveness of certain chemotherapies. With a Fiscal Year 2018 Career Development Award, Dr. Abbosh investigated the bacterial microenvironment in bladder cancer to associate presence of certain microbes with chemotherapy response or lack of response.

The team found E. coli was unexpectedly common in the urine specimens from bladder cancer patients. Recently, the class of bacteria called gammaproteobacteria, of which E. coli is a member, was shown to metabolize a commonly used chemotherapy, gemcitabine, in patients with pancreatic cancer1, leading Dr. Abbosh and team to suspect that a similar phenomenon may be occurring in bladder cancer patients since the drug is frequently used for this disease as well. The research team is currently investigating this phenomenon in bladder cancer. Other bacteria were also found in the bladders and urine of bladder cancer patients. Campylobacter ureolyticus and the Akkermansia mucinaphila were detected and are suspected to affect the response to bladder cancer treatments. This is also currently under investigation.

If successful, the findings could lead to clinical trials manipulating the bladder or the bladder cancer microbiome to enhance responses to treatment. Enhancing the response to chemotherapy in this way could lead to curing the cancer without removal of the bladder and improvements in the long-term quality of life for these patients.

1Geller LT, Barzily-Rokni M, Danino T, et al. 2017. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science Sep 15;357(6356):1156-1160. doi: 10.1126/science.aah5043. PMID: 28912244; PMCID: PMC5727343.

Links :
Public and Technical Abstracts: Immunologic and Microbial Correlates and Mechanisms of Complete Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

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Last updated Tuesday, June 7, 2022