BCAN's Funded Research Awards

Filipe De Carvalho, MD, PhD

Urologic Oncology Fellow; Clinical Assistant Professor, Division of Urology

Institution:
Brigham and Women's Hospital

Research:

Tumor-associated macrophage reprogramming through PARP14 inhibition in muscle-invasive bladder cancer

Summary:

Background 

In 2022, more than 82,000 people in the United States were diagnosed with bladder cancer. Most of these cancers are found early and can often be cured by removing the tumor. However, about one in four people are diagnosed with a more serious type called muscle-invasive bladder cancer. This form grows deep into the bladder wall and is harder to treat. Patients with this kind of cancer usually receive chemotherapy, immunotherapy, or both. Some patients respond well to these treatments, but sadly, fewer than one in three see their tumors shrink. For those whose cancer continues to grow despite treatment, the outlook is often poor. 

What the Study Proposes to Address 

This study focuses on understanding why some bladder cancers do not respond to chemotherapy or immunotherapy. Early research found that tumors resistant to treatment often have large numbers of certain immune cells called tumor-associated macrophages. These cells can protect the cancer from the immune system, making it harder for treatments to work. The researcher aims to find ways to target and control these macrophages to make chemotherapy and immunotherapy more effective. The study will also map where these cells are located within bladder tumors to help identify which patients might benefit from this new approach. 

Why This Research is Important 

By studying how tumor-associated macrophages affect treatment, this research could lead to new ways to overcome resistance to current therapies. Understanding which patients are most likely to respond to macrophage-targeted treatments could help doctors personalize care and improve survival rates. The findings from this work may also guide future clinical trials and lead to new treatment strategies that give hope to patients and families affected by advanced bladder cancer. 

Clonal Architecture and Tumor Microenvironment of Cisplatin Resistant Localized Muscle Invasive Bladder Cancer

Summary:

Background 

Bladder cancer is one of the most common cancers in the United States, with more than 81,000 new cases diagnosed in 2020. Most bladder cancers are caught early and can be cured by removing the tumor. But about 25% of patients are diagnosed with a more serious form called muscle-invasive bladder cancer (MIBC), which grows deep into the bladder wall. This type of cancer is dangerous and usually requires chemotherapy followed by removal of the bladder. 

Patients whose tumors shrink or disappear with chemotherapy have a good chance of being cured. Unfortunately, fewer than one in three patients respond this well. Those whose tumors remain deep in the bladder after treatment often face very poor outcomes. 

What This Research Proposes to Address 

Scientists have discovered that changes in DNA, called mutations, may affect how tumors respond to chemotherapy, but the connection is not yet clear. A new technology called single-cell sequencing allows researchers to look at the DNA of individual cancer cells. This makes it possible to see how different cells within the same tumor behave and why some resist treatment. 

The researchers will compare tumors that responded well to chemotherapy with those that grew worse during treatment. Using single-cell sequencing, they hope to identify exactly how resistant tumors escape the effects of chemotherapy. 

Why This Research Is Important 

By learning how tumors resist treatment, researchers can find better ways to match patients with the therapies most likely to help them. This could spare patients from going through chemotherapy that is unlikely to work and its harmful side effects. It could also guide doctors to recommend other treatments, like immunotherapy, sooner.  

In the long run, this project could give patients more personalized treatment plans, improve survival rates, and reduce the suffering caused by ineffective therapies. 

Citations:

Carvalho, F. L. F., Wang, Y., Dall, C. P., Nayan, M., Chou, W. H., McGregor, B., Stopfkuchen-Evans, M. F., Stamatakis, L., Preston, M. A., Kibel, A. S., Chang, S. L., & Mossanen, M. (2022). Preoperative anemia is associated with increased radical cystectomy complications. Urologic oncology, 40(8), 382.e7–382.e13. https://doi.org/10.1016/j.urolonc.2022.04.014

Mossanen, M., Carvalho, F. L. F., Muralidhar, V., Preston, M. A., Reardon, B., Conway, J. R., Curran, C., Freeman, D., Sha, S., Sonpavde, G., Hirsch, M., Kibel, A. S., Van Allen, E. M., & Mouw, K. W. (2022). Genomic Features of Muscle-invasive Bladder Cancer Arising After Prostate Radiotherapy. European urology, 81(5), 466–473. https://doi.org/10.1016/j.eururo.2021.12.004

Additional Research:

None Reported as of August 2025

Project Collaborators:

NA

Project Status:
Completed