The 2004 World Health Report attributed approximately 179,000 deaths worldwide each year due to urinary bladder tumors, the seventh most prevalent type of cancer worldwide. I am mainly involved in investigating the molecular biology of urothelial cancers, and how this information can be used for better patient management and to identify potential therapeutic targets. Several of these investigations and other research efforts in a variety of urologic malignancies are in collaboration with the USC Institute of Urology. Some of the projects that I am involved in are as follows:
Identification of gene expression profiles that can predict bladder cancer outcome: Using medium-high throughput technologies and advanced bioinformatics, I have adopted pathway-specific approaches to profile genes implicated in major bladder tumorigenic pathways as represented in the figure below. Using a supervised genetic programming algorithm, we have identified an expression signature that can predict nodal metastasis in bladder cancer (access study here). We have also used this approach to successfully and reproducibly identify expression panels that can reliably predict clinical outcome in noninvasive and invasive bladder cancer.
Marker panel employed for standardized competitive RT-PCR analysis. The primary effector pathways of tumorigenesis encompass apoptosis, cell cycle, gene regulation, cell growth regulation and anti-oxidation. There is a significant overlap of markers among the first three pathways. The secondary effector pathways include signal transduction, angiogenesis and invasion. All the listed genes exert stimulatory, inhibitory and/or regulatory effects on their respective pathway(s). See high resolution version of the above image here.
Understanding the effects of smoking and NSAID use on bladder cancer progression: I am investigating the detrimental molecular effects of smoking on bladder urothelium and how it contributes to bladder cancer progression. I am also conducting clinical studies to investigate the potential of non-steroidal anti-inflammatory drugs (NSAIDs) in lowering the risk of progression in bladder cancer. These studies are supported by the Genito-Urinary Oncology Research Program at the USC/Norris Comprehensive Cancer Center.
Examining alterations in the p53 pathway in invasive bladder cancer: The role of p53 pathway alterations in invasive bladder cancer has been extensively investigated. However, discrepancies in the p53 gene and protein status have been noted in bladder tumors, and this has a bearing on patient outcome. I am conducting studies that try to define the reasons behind these discrepancies, and how they can affect patient management. These studies are in collaboration with the USC Institute of Urology.
Analyzing the effect of p53 alterations on chemotherapeutic response in bladder cancer: I am involved in the international, multicenter p53-targeted therapy trial, the first bladder cancer clinical trial that targeted a molecular lesion. This trial examined effects of p53 alterations on response to chemotherapeutic regimens that include the DNA-damaging agent, cisplatin (in addition to methotrexate, vinblastine and adriamycin). While the initial results were not encouraging, they were highly dependent on the tumor's p53 protein status, which has been shown to only partially predict outcome. I am delving deeper into the tumors' biology in an effort to identify stronger predictors of chemotherapeutic response in these patients.
Identifying prognostic clinical parameters and constructing predictive models for genitourinary malignancies: In partnership with the USC Institute of Urology and other collaborators, I am working to define clinical predictors of oncological endpoints in large patient cohorts.
Last Modified: August 2011
© Anirban Mitra 2009-2014