UAB Comprehensive Cancer Center Magazine - Spring 2016 - Page 14

quick takes RESE ARCH BRIEFS Ovarian Cancer Survival Rates Do Not Rise with Paclitaxel A recent study published in The New England Journal of Medicine found that administering the cancer drug paclitaxel weekly versus every three weeks does not prolong progressionfree survival among patients with ovarian cancer. Paclitaxel, an anti-cancer chemotherapy drug, is commonly used to treat ovarian, breast, lung, pancreatic and other cancers. Weekly paclitaxel therapy has been shown to prolong survival among patients with early-stage breast cancer and those with metastatic breast cancer, but its effect in ovarian cancer was unknown. For this large, multinational study, UAB investigators looked at the combined dose-dense weekly paclitaxel with the drug bevacizumab. Overall, results show that a regimen of weekly paclitaxel did not prolong progression-free survival (PFS) as compared with a regimen of treatment every three weeks. Results also indicated patients who did not receive bevacizumab with a weekly dosage of paclitaxel saw a PFS that was 3.9 months longer than those receiving paclitaxel every three weeks. UAB was a lead enrollment site for this trial, which involved 692 patients with newly diagnosed, previously untreated ovarian cancer at more than 209 clinics in the United States, Canada and South Korea. New Pathway Sheds Light on Some Cancers In humans, the differentiation of stem cells into hundreds of specialized cell types is vital. Differentiation drives development from fertilized egg to a newborn, and it underlies the continuous replacement of the five billion cells that die every hour in an adult. On the downside, mutations in differentiation pathways of different cell types can be drivers of cancers. Xinyang Zhao, Ph.D., and colleagues Li Zhang, Ngoc-Tung Tran and Hairui Su at UAB and at seven other institutions, have discovered a new mechanism of differentiation, as studied in megakaryocytes, the blood cells responsible for platelet production. This mechanism may offer new research and therapeutic approaches to blood malignancies as well as solid tumors such as colon and breast cancers. Since two of the key proteins in the pathway — PRMT1 and RBM15 — are expressed in all tissues, they may also regulate differentiation in other tissues, especially those where RBM15 has been shown to be essential for development, including the heart, spleen and placenta. The pathway is complex to describe, but its ultimate effect is an alternative splicing of messenger RNAs — particularly the messenger RNAs of master regulators called transcription factors. These factors control the reading of genetic information from DNA genes and act as switches in all living organisms to control gene expression. The work by Dr. Zhao, a Cancer Center associate scientist, and his colleagues, publis hed online in advance of print in eLife, has taken four years. UAB Study Hailed Among Best in Cancer Research Mona Fouad, M.D., M.P.H. Research led by Mona Fouad, M.D., M.P.H., director of the UAB Division of Preventive Medicine, has been selected by the American Society of Clinical Oncology for inclusion in Clinical Care Advances 2016, the society’s annual review of progress against cancer and emerging trends in the field. The study, titled “Patient navigation as a model to increase minority participation in cancer clinical trials,” examines the use of patient navigators for informing and enrolling potentially eligible African-American patients in clinical trials. To be successful, cancer clinical trials require participation of individuals from all population groups. Enrollment and retention are especially challenging among racial and ethnic minorities. Currently, less than 10 percent of all trial participants are minorities. For this study, lay individuals who are not medical professionals were hired and trained to serve as patient navigators. African-American patients potentially eligible for clinical trials were identified through chart reviews and referrals by clinic nurses, physicians and social workers. The navigators met with the patients, informed them about current clinical trials, and provided tailored support to those who decided to enroll in a trial. Between 2007 and 2014, of 378 African-Americans who were eligible for a clinical trial, 304 enrolled in one and 272 opted to receive patient navigation support. Among trial participants receiving navigation support, 75 percent completed the trial compared to 38 percent of trial participants not receiving navigation support. The difference in retention rates between the two groups was statistically significant, and participation of African-Americans in cancer clinical trials increased from 9 percent to 16 percent. “Although future studies need to evaluate clinical trial participation with other racial and ethnic minorities, this model holds promise as a strategy to reduce disparities in cancer clinical trial participation,” Dr. Fouad says. 24 U A B C O M P R E H E N S I V E C A N C E R C E N T E R PATIENT AND FAMILY RESOURCE CENTER Promising Leukemia Marker Found The UAB Comprehensive Cancer Center’s Patient & Family Resource Center provides a comfortable place to find support. If you or a loved one has been diagnosed with cancer, our staff can answer your questions about the illness, treatment options and available support services. UAB researchers have found a marker on blood cells that may help the most pressing problem in chronic myelogenous leukemia (CML) today — an inability to get patients off treatment. “To do that, we have to be able to maintain their remission after stopping treatment,” says Ravi Bhatia, M.D., director of the UAB Division of Hematology-Oncology and Cancer Center deputy director. “Treatment using drugs called tyrosine kinase inhibitors, or TKIs, do not eliminate leukemia-initiating cells.” In most patients, residual leukemia-initiating cells result in Ravi Bhatia, M.D. regeneration of leukemia, necessitating lifelong treatment with these drugs. Only a small proportion of CML patients stay in remission after stopping TKI treatment. Two keys to containing remission may be the ability to identify those patients who will be able to successfully stop their TKI without later relapse and, second, the ability to identify patients who may benefit from an additional drug regimen besides TKI to achieve treatment-free remission. Research by Dr. Bhatia and colleagues, published in The Journal of Clinical Investigation, shows that the leukemia-initiating stem cells in the bone marrow are not uniform. Instead, evidence points to a mixed population of cells that can be distinguished by several cell markers, significantly Mpl gene expression. Cells with high Mpl gene expression are prone to initiating the disease-causing profusion of white blood cells in animal models of CML. Over the past 15 years, CML has had a marked improvement in five-year survival thanks to TKI drugs, from about 30 percent to nearly 90 percent today. However, the drugs have to be taken every day for a patient’s lifetime, and their yearly cost can be $100,000 to $150,000. This is a societal burden, and for some patients the drug co-payments can exceed their ability to pay. Identifying those who could safely stop TKI treatment would be a boon to patients and society. This can include: n Cancer Prevention n Dealing with Side Effects n Clinical Trials n Complementary Therapies n Stress Management n Spirituality UAB Researchers Identify Key Protein in Brain Cancer n Support Groups & Oneon-One Support A team of UAB physicians and scientists recently discovered that a kinase protein known as MLK4 plays a crucial role in survival of patient-derived brain cancer stem cells in pre-clinical animal models. These findings suggest that MLK4 could potentially be a useful target for cancer treatment. Protein kinases are key regulators of cell function that constitute one of the largest and most functionally diverse gene families. Until recently, MLK4 was considered a poorly characterized kinase. The UAB team, however, identified this gene from a stepwise screening of molecules that are elevated in cancer stem cells isolated from brain cancer patients. The findings, published in Cancer Cell, nailed down the novel molecular mechanisms for which MLK4 is essential in cancer stem cells and not in normal cells in the human body. Most importantly, brain cancer patients with higher MLK4 expression have shorter survival despite the current intensive therapies including surgery, chemotherapy and radiotherapy. Nonetheless, there are no MLK4-targeting therapies or clinical trials currently available for patients. “There is no doubt that society desperately needs new and effective therapies for this lifethreatening brain disease. Improvement of patient survival for the past 50 years has been counted by months and not years,” says Ichiro Nakano, M.D., Ph.D., professor in the UAB Department of Neurosurgery and principal investigator of the study. “We, as an international collaborative team centered at UAB, focus on cancer stem cells as a therapeutic target in brain cancers.” Collaborative participants on this project include M.D. Anderson, Ohio State University, University of Texas, Northwestern University, Cincinnati Hospital Medical Center, and a variety of German and Japanese research departments and institutes. The work was supported by the American Cancer Society, the Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and Takeda Science Foundation. # K N O W U A B C C C n Mindful Meditation n Restorative Yoga n Art Therapy PATIENT & FAMILY RESOURCE CENTER Wallace Tumor Institute, Room 220 For more information, contact Teri Hoenemeyer, (205) 934-5772 tgw318@uab.edu • U A B . E D U / C A N C E R 25