The Johns Hopkins Greenberg Bladder Cancer Institute awarded research grants to four projects that focus on understanding how treatment of bladder cancer affects women, why the disease has a less favorable outcome for women than men, and how biology could play a role in offering new targets for cancer therapy.

The institute encourages new strategies for combating bladder cancer and rewards those areas of innovative study with grants of $25,000 to $50,000. David McConkey, Ph.D., director of the Greenberg Bladder Cancer Institute, says it was not happenstance that some of the projects selected this year focus on women’s bladder cancer.

“Bladder cancer presents different clinical challenges in men and women. It is diagnosed more often in men, but on average, women develop more aggressive disease,” says McConkey. “Identifying the root causes of these discrepancies is a top priority for ongoing research. We also need to optimize our surgical approaches in men and women to ensure that we are obtaining the best possible outcomes. The projects we are funding this year directly address both of these priorities.”

The Greenberg Bladder Cancer Institute recently launched a women’s bladder program at the Johns Hopkins Kimmel Cancer Center. Jean Hoffman-Censits, M.D., and Armine Smith, M.D., will lead the program.

Two of the projects awarded research grants are looking at how bladder cancer treatment impacts the sexual health of women and how women are counseled after undergoing radical cystectomy, a surgical procedure during which the bladder and, typically, the uterus, ovaries and part of the vagina, are removed.

Natasha Gupta, M.D., is a resident at the Brady Urological Institute at the Johns Hopkins University School of Medicine. Her project aims to examine the components of sexual health and dysfunction among women with bladder cancer who undergo radical cystectomy, as well as the counseling patients receive regarding these issues.

“I am grateful for the resources and support provided by the Greenberg Bladder Cancer Institute,” says Gupta. “They have allowed me to design and conduct studies to understand the important but poorly understood topic of sexual health and dysfunction among women with bladder cancer.”

Gupta and her team will also study national practice patterns among urologists regarding radical cystectomy in women and counseling about sexual dysfunction. They are conducting in-depth interviews with patients and their partners about these issues.

Gupta hopes a better understanding of sexual health and dysfunction in women with bladder cancer will lead to improved decision making about treatment and better management of sexual dysfunction in patients who undergo radical cystectomy for bladder cancer.

Sima Porten, M.D., M.P.H., is a member of the urologic oncology team at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. Sumeet Bhanvadia, M.D., is an assistant professor of clinical urology at the Keck School of Medicine at the University of Southern California. The two want to do an in-depth assessment of sexual outcomes among women after radial cystectomy to understand the extent of sexual dysfunction and its impact on patients and their partners.

“We are honored to have received this award from the Johns Hopkins Greenberg Bladder Cancer Institute,” Porten says. “We believe this will help us address an unmet need and improve the care for women with bladder cancer.”

Their pilot study hopes to generate data to develop a quantitative measure of degrees of sexual dysfunction and quality of life issues among women with bladder cancer. This information can be used to develop alternative treatment plans and properly prepare patients for what they may experience after radical cystectomy.

Margaret Knowles, Ph.D., at the University of Leeds, and Benjamin Hopkins, a Ph.D. student at Leeds, have identified biological differences between cultured normal cells from the bladders of men and women.

“Such differences may have a major influence on the process of tumor development,” Knowles says. “This award will allow us to examine normal cells directly isolated from the bladders of normal males and females to determine whether such differences also exist within the body.”

While acknowledging that different exposure risks have been highlighted, Knowles and her team suggest a complete explanation for the gender-related differences in bladder tumor behavior relates to genetic and epigenetic distinctions in these tumors, and such differences may develop because of inherent differences in the biology of the normal male and female bladder.

Their goal is to make it possible for treatments to target the specific biology of tumors, taking into account any gender-related differences.

Jenny Southgate, Ph.D., director of the Jack Birch Unit for Molecular Carcinogenesis at the University of York, and Simon Baker, Ph.D., deputy director of the Jack Birch Unit, are examining how the skin layers inside the bladder—known as urothelial cells—develop and how those cells have genetic qualities seen in some subsets of bladder cancer.

“We are absolutely delighted to have been awarded the grant from the Johns Hopkins Greenberg Bladder Cancer Institute. It is a particularly exciting time for bladder cancer research, with the international surge of interest in this long ignored but important cancer and with much recent progress in establishing different disease subgroups,” Southgate says. “From our particular perspective of normal bladder biology, our study aims to explain the different ways bladder cells use their genes when exposed to different stimulations in the laboratory, which will offer new targets for cancer therapy.”

Southgate and Baker will look at receptors in the urothelial cells—turning them on and off—to discover what role they may have in tumor development. They believe their work will provide new insights into bladder cancer subtypes and a new understanding of urothelial biology.