From Ideas to Impact

Pelotonia’s impact is perhaps most obvious in discoveries made and initiatives launched by teams of researchers who have received support from Pelotonia revenue over the past four years. Some examples:

With a Pelotonia Idea Grant as partial support, a team of OSUCCC – James researchers has linked a stress gene called ATF3 in immune cells to breast cancer metastasis, a process of spreading cancer cells from a tumor to other parts of the body. Metastasis is the major cause of death in cancer patients. The researchers say their study suggests that ATF3 may be the crucial link between stress and cancer. Previous studies have shown that stress is a risk factor for cancer. This research suggests that cancer cells, by acting as stress signals, coax immune cells that have been recruited to a tumor to express ATF3. Though it’s unclear how, ATF3 promotes the immune cells to act erratically and give cancer an escape route from the tumor site to other areas of the body. “If your body does not help cancer cells, they cannot spread as far,” says Tsonwin Hai, PhD, senior author of the study, which was published in the Journal of Clinical Investigation. “So the rest of the cells in the body help cancer cells move to distant sites. And one of the unifying themes is stress.” Hai says this stress gene could one day function as a drug target to combat cancer metastasis.

Researchers at the OSUCCC – James have discovered a mechanism responsible for the loss of a critical tumor-suppressor gene called A20 in rhabdomyosarcoma and other soft-tissue sarcomas – rare cancers that strike mainly children and often respond poorly to treatment. Knowledge of the mechanism could guide the development of more effective therapies for these malignancies. The researchers found that A20 is silenced not by mutation, as in many other cancers, but because a second molecule is lost – a small molecule called microRNA-29. They also found that microRNA-29 normally protects A20 from destruction. When microRNA-29 is absent, A20 is degraded. Loss of A20, in turn, leads to a rise in levels of a protein called NF-κB and to tumor progression. The findings were published in the journal Science Signaling. “We know that NF-κB is a tumor promoter, but we don’t know why it is up-regulated in many cancers,” says principal investigator Denis Guttridge, PhD. “Our study indicates that it involves a regulatory circuit between NF-κB, microRNA-29 and the A20 tumor-suppressor gene. It also identifies NF-κB as a therapeutic target in sarcoma, and A20 and microRNA-29 as potential biomarkers for sarcoma.” First author Mumtaz Yaseen Balkhi, PhD, a former Pelotonia fellowship recipient, says the findings move research a step closer toward developing microRNA-29 therapy against NF-κB activation in cancers.

A study supported in part by Pelotonia dollars identified microRNA-155 as a new independent prognostic marker and treatment target in patients with acute myeloid leukemia that has normal-looking chromosomes under the microscope (called cytogenetically normal acute myeloid leukemia, or CN-AML). The study found that when microRNA-155 is present at abnormally high levels in CN-AML cells, patients are less likely to have a complete remission, and they experience a shorter disease-free period and shorter overall survival. Published in the Journal of Clinical Oncology, the findings suggest that miR-155 plays a pivotal role in CN-AML development and could be a valuable target for an emerging class of drugs designed to inhibit microRNAs. The researchers say miR-155 would be relatively easy to measure at the time of diagnosis. They believe it will prove to be a good marker for stratifying patients according to recurrence risk and a good target for emerging compounds designed to inhibit microRNAs. Senior author Clara D. Bloomfield, MD, notes that, overall, “Our findings indicate that miR-155 expression is a strong and independent prognostic marker in CN-AML, and they provide clinical validation of data from preclinical models that support a crucial role of miR-155 in leukemia.”

Pelotonia dollars have helped the OSUCCC – James launch a statewide initiative to screen newly diagnosed colorectal cancer (CRC) patients and their biological relatives for Lynch syndrome (LS), a major cause of inherited colorectal, ovarian and uterine cancer. This effort, called the Ohio Colorectal Cancer Prevention Initiative (OCCPI), reveals others who may be at risk of developing these cancers so they can take precautionary measures. The initiative is led by Heather Hampel, a certified genetic counselor at Ohio State. Hampel says about 3 percent of CRC cases result from LS, which is characterized by inherited mutations in certain genes. Each CRC patient found to have LS has, on average, an additional three relatives with LS.

The OCCPI includes around 40 hospitals from throughout Ohio that have implemented the LS screening program. The partner hospitals advise patients and their physicians of the results, offer genetic counseling and make cancer surveillance recommendations to patients and family members found to have LS. “If you find people with LS before they get cancer, you have the potential to really save lives,” says Hampel, explaining that these patients can have colonoscopies earlier and more frequently so precancerous polyps can be detected and removed, or so cancer can be detected early when it is more treatable. Hospitals participating in the OCCPI include:

Cleveland Clinic Foundation, James Cancer Hospital and Solove Research Institute, Riverside Methodist Hospital (Columbus), The Christ Hospital (Cincinnati), Mount Carmel East (Columbus), Summa Akron City/St. Thomas Hospital (Akron), Aultman Hospital (Canton), Kettering Medical Center (Dayton), Miami Valley Hospital (Dayton), Bethesda North Hospital-TriHealth (Cincinnati), ProMedica Toledo Hospital, Hillcrest Hospital (Mayfield Heights), Mount Carmel West (Columbus), St. Rita’s Medical Center (Lima), Good Samaritan Hospital-TriHealth (Cincinnati), MetroHealth System (Cleveland), Genesis Healthcare System (Zanesville), ProMedica Flower Hospital (Sylvania), Fairview Hospital (Cleveland), Good Samaritan Hospital (Dayton), Akron General Medical Center, Mercy Medical Center (Canton), Springfield Regional Medical Center, Blanchard Valley Regional Health Center (Findlay), Upper Valley Medical Center (Troy), Atrium Medical Center (Middletown), Adena Health System (Chillicothe), Robinson Memorial Hospital (Ravenna), Mount Carmel St. Ann’s (Westerville), Southern Ohio Medical Center (Portsmouth), Grant Medical Center (Columbus), Marietta Memorial Hospital, Summa Barberton Hospital, Doctors Hospital West (Columbus), Licking Memorial Hospital (Newark), Knox Community Hospital (Mount Vernon), Grady Memorial Hospital (Delaware), Summa Western Reserve (Cuyahoga Falls), Wayne Hospital (Greenville), ProMedica St. Luke’s Hospital (Maumee).

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