Innovative University of Cincinnati-based cancer research concepts are able to move forward, thanks to the tireless fundraising efforts of Marlene Harris-Ride Cincinnati, a nonprofit organization founded in 2007 to raise money to fund promising breast cancer research projects proposed by basic scientists affiliated with the UC Cancer Institute.
Ride Cincinnati founders Harvey Harris, DDS, and Alison Gordon, and other executive committee members visited UC on Oct. 24, 2011, to present a $200,000 check for the 2011 event’s proceeds to William Barrett, MD, chair of the UC College of Medicine’s radiation oncology department and medical director for the UC Health Barrett Center.
Since its inception, Ride Cincinnati has raised more than $1 million for cancer research through an annual cycling event known by the same name—with the majority of that money going to the UC Cancer Institute for breast cancer research.
"We recognize that progress in the fight against breast cancer will only be made through research,” says Harris. Ride Cincinnati was founded in honor of his late wife,Marlene Harris, who died of breast cancer. "It’s important to support those efforts, particularly right here in Cincinnati.”
Adds UC Cancer Institute Director George Atweh, MD: "Securing funding to pursue promising but untested ideas can be challenging. Ride Cincinnati offers important seed funding to scientists with potentially impactful new ideas. That financial boost is critical to get the idea off the ground and eventually lead to larger grants.”
2011/2012 Ride Cincinnati Pilot Grants Program
Ride Cincinnati has awarded a total of $200,000 to researchers at the UC College of Medicine this year. Projects include:
Investigator: El Mustapha Bahassi, PhD, research assistant professor, Department of Internal Medicine – Division of Hematology Oncology
Project: Preclinical and clinical evaluation of the PARP inhibitor iniparib in DNA damage checkpoint Chk2 mutant breast cancer
BRCA1 and BRCA2 were identified as tumor-suppressor genes responsible for a significant proportion of hereditary breast cancers in the 1990s and both are involved in DNA damage repair. Recently drugs that obstruct repair pathways have begun to enter clinical trials—the first inhibitor of this type to reach a phase 3 clinical trial is iniparib, which inhibits an enzyme known as PARP1. Preliminary studies have shown that when both the BRCA1/BRCA2 and PARP repair pathways are disabled, the unrepaired DNA can lead to the death of the cell – selectively inducing cancerous cell death and sparing normal cells. In this new study, Bahassi and his colleagues Olivier Rixe, MD, PhD, and Mahmoud Charif, MD, will expand the use of PARP inhibitors beyond BRCA deficiency by testing other DNA damage repair-deficient lesions and their ability to cause drug sensitivity in human breast cancer cells and mouse tumor xenografts.
Investigator: Nelson Horseman, PhD, professor, Department of Molecular and Cellular Physiology
Project: Bone Metastasis, Serotonin Drives PTHrP and Runx2
Horseman’s lab discovered that serotonin (5-HT) is synthesized by breast epithelial cells and acts as an autocrine-parcrine regulator of normal breast cells and breast cancer. His lab’s most recent discoveries have shown that 5-HT drives the expression of critical bone regulating genes in human breast cancer cells. The overall results imply that autocrine 5-HT signaling is responsible for the tendency of breast cancers to metastasize preferentially to bone. In this next step of research, Horseman and his team will extend their functional and cellular discoveries into preclinical models of in vivo human breast cancer to bridge a critical knowledge gap. The seed money will allow Horseman to collect the scientific evidence necessary to design a clinical trial protocol to test the efficacy of suppressing bone cancers metastases by interfering with 5-HT signaling.
Investigator: Nira Ben-Jonathan, PhD, professor, Department of Cancer and Cell Biology
Project: Mammolactin—a novel biomarker in breast cancer
Early studies have detected immunoreactive placental lactogen (hPL) in breast cancers and in serum from some breast cancers. Ben-Jonathan’s lab previously found that hPL in several breast cancer lines but not in non-malignant breast epithelial cells or antibodies against it. She believes that this specific hPL protein hormone—now called mammolactin—is uniquely produced and secreted by breast cancer and therefore can serve as a biomarker for the disease. This project will aim to generate appropriate tools for the examining its presence in serum and tumor samples from breast cancer patients versus controls. The hope is that this will lead to a selective breast cancer biomarker that can support diagnosis/prognosis, provide surveillance after surgery, predict tumor responsiveness to chemotherapy, etc.
Investigator: Sang-Oh Yoon, PhD, assistant professor, Department of Cancer and Cell Biology
Project: Molecular Mechanism of mTOR Regulation and Its Function in Breast Cancer
Investigator: Elyse Lower, MD, Cincinnati-Based Oncologist
Yoon will be investigating the mTOR/S6K1 signaling pathway—a central regulator of cell growth and proliferation that when deregulated in breast cancer plays a critical role in disease progression. It also has a strong association with poor prognosis, resistance to multiple therapies and increased mortality. Current mTOR inhibitors, however, only have mild effects on breast cancer, despite the fact that mTOR is a "master regulator of metabolism, proliferation, survival and growth in breast cancer.” Yoon will seek to understand why mTOR inhibitors do not have a strong effect on breast cancer cells and how to increase their efficacy in the treatment of breast cancer patients by identifying and characterizing the molecular mechanisms behind the signaling pathway in breast cancer.
Assessment of Adjuvant "Hormone-Therapy Fatigue" in Breast Cancer
Lower is conducting a study to determine
the prevalence of cognitive impairment, including fatigue, in
premenopausal and postmenopausal breast cancer patients prior to
initiating adjuvant hormone treatment for breast cancer. She will also assess cognitive
impairment during adjuvant hormone treatment and seek to determine the
interaction between fatigue and other factors of cognitive dysfunction,
including depression and sleepiness.
The Marlene Harris-Ride Cincinnati Pilot Grant Program is part of the Cincinnati Cancer Center, a joint cancer program involving the UC Cancer Institute, Cancer and Blood Diseases Institute at Cincinnati Children’s Hospital Medical Center and UC Health. The collaborative initiative brings together interdisciplinary research teams of caring scientists and health professionals to research and develop new cures, while providing a continuum of care for children, adults and families with cancer.