Kendra Marr, a fifth-year MD/Ph.D. student at the University of Arizona College of Medicine in Tucson, Arizona has received a National Research Service Award (grant) from the National Cancer Institute (NCI) totaling US $ 174,728.00 to study how prostate cancer spreads through the smooth muscle surrounding the prostate gland.

She spent nearly two years developing the project throughout a highly competitive grant submission process before it was recently awarded funding.

As part of her study, Marr seeks to understand and address prognosis, one of the unique challenges presented by prostate cancer.

“This is a dream come true for me,” Marr said.

“One of the main goals I had in pursuing a Ph.D. was to learn to write my own grant. I feel like it has been five years in the making, but it is a sense of fulfillment knowing how much hard work I put into this. Now I am energized and motivated to move this research forward.”

Integrins
Marr works in the laboratory with Anne Cress, Ph.D., a UArizona Cancer member in the Cancer Biology Program, who has long studied how tumors metastasize or move through the body. In studying this, Cress has been interested in a group of adhesive receptors called integrins, which are adhesion molecules that tumors use to move to a distant site in the body.[1]

These integrins, which are transmembrane receptors for extracellular matrix proteins, play a crucial role in cell survival, proliferation, migration, gene expression, and activation of growth factor receptors. But in some cancers, including prostate cancer, their functions and expressions are deregulated. This deregulation has profound consequences, given the ability of each integrin to regulate specific cell functions.[1]

“We know a lot about how integrins work and what they do,” Cress said.

Kendra Marr is a fifth-year MD/Ph.D. student at the University of Arizona College of Medicine in Tucson, Arizona has received a National Research Service Award (grant) from the National Cancer Institute (NCI) totaling US $ 174,728.00 to study how prostate cancer spreads through the smooth muscle surrounding the prostate gland. Photo Courtesy: ® 2020 University of Arizona College of Medicine in Tucson.

“They attach and release as Velcro comes on and off. But we now realize that they are not only adhesion receptors; in fact, they actually sense the biophysical environment, and this changes how they work,” she added.

Prostate drivers
This understanding becomes central to Marr’s research because of the anatomy of the prostate. A small, reproductive gland located at the base of the bladder, the prostate is surrounded by a capsule made of smooth muscle. In order for cancer to spread from the prostate to surrounding tissue or organs, it must pass through the muscle layer.

The project will investigate why a specific tumor invades through the smooth muscle capsule while a different tumor may not spread from the prostate and may not require treatment.

When cancer escapes the gland, it can extend to the intestine, bladder, or bones, which causes an increased risk of morbidity. However, overtreatment can be a concern for patients who receive treatment for cancer that is considered low risk and would have never caused symptoms. Overtreatment can lead to problems and harmful side effects that could have been avoided.

Prevalence
According to the Centers for Disease Control and Prevention (CDC), prostate cancer is the most prevalent non-skin cancer and the second most deadly cancer for American men.

In 2017, the latest year for which incidence data are available, in the United States, 207,430 new cases of Prostate Cancer were reported among men, and 30,486 men died of this cancer. For every 100,000 men, 107 new Prostate Cancer cases were reported and 19 men died of this cancer. [2]

When confined to the prostate, the five-year survival for prostate cancer is near 100 percent. However, that percentage drops to 30% if cancer spreads to a distant site, according to the National Cancer Institute (NCI).

“The goal is to improve the standard of care for prostate cancer patients,” Marr explained. “We want to close the gap in knowledge for diagnosing cancer that requires treatment and which cancer may be best to simply watch. If we can find molecular markers or discriminators of indolent disease that is going to remain in the gland versus aggressive disease, then that is what can inform treatment decisions,” she added.

Knowledge, skills, and experiences
As an MD/Ph.D. student, Marr is developing a balanced combination of knowledge, skills, and experiences for both understanding basic science and bridging that to the clinical setting. In addition to Cress, Marr’s mentors for the project include Cancer Center members Edward P. Gelmann, MD, Benjamin Lee, MD, and Hina Arif Tiwari, MD. Application assistance was provided by the internal Cancer Center grant review support team, led by Keith Maggert, Ph.D.

“It is important for us to train physician-scientists for the next generation of researchers,” Cress noted. “The NCI grant supports that mission and gives someone like Kendra the opportunity to move the field forward. That only happens in a setting like this through the UArizona’s NCI-designated Comprehensive Cancer Center and our College of Medicine.”

Cress believes that the hard work put forth by Marr can have a “multiplier effect” on others in pursuit of their own research and writing grants. Marr is more than willing to do her part for her peers.

“I have so many incredible mentors,” Marr noted.

“I can’t thank them enough for helping me get to this point. And I certainly want to be able to support my underclassmen and my program, too. A big wish of mine is to help other students in their journey towards applying for these types of grants,” she concluded.

Reference
[1] Goel HL, Li J, Kogan S, Languino LR. Integrins in prostate cancer progression. Endocr Relat Cancer. 2008;15(3):657-664. doi:10.1677/ERC-08-0019
[2] Leading Cancer Cases and Deaths, All Races/Ethnicities, Male, 2017. Prostate Cancer. Online. Last accessed on September 9, 2020.

Featured image: Tucson, AZ. Photo Courtesy: ® 2020 University of Arizona College of Medicine in Tucson.

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