Grantee Spotlight: Harold "Bo" Netwon Lovvorn, III, M.D. - Molecular Analysis of Ethnic Variations in Wilms tumor
September 18, 2014, by CRCHD Staff
Cancers that develop in children are often different from those diagnosed in adults, and usually are a result of DNA changes that naturally happen throughout a child's growth periods, and sometimes, even before they are born. Thus, efforts to identify successful and effective treatments for this vulnerable group require a specific focus at the molecular level to aid in understanding childhood cancers.
Harold Newton "Bo" Lovvorn, III, M.D., Assistant Professor of Pediatric Surgery at Vanderbilt University Medical Center, a CRCHD R21 workforce diversity grantee , is taking his pediatric cancer research even further - to include child cancer patients from underrepresented ethnic backgrounds. In so doing, he is seeking to ensure that pediatric cancer health research will be beneficial to all children, regardless of background.
Lovvorn's research focuses particularly on Wilms Tumor (WT), also known as nephroblastoma, which forms in the kidneys and often metastasizes to the lung, and sometimes to the liver. While most children survive from the rare kidney cancer (only 500 cases are diagnosed in the U.S. per year), there still remains a group of children who suffer from the disease at higher rates than others. Children of black sub-Saharan African ancestry are affected most commonly from the disease.
"Wilms Tumor has been recognized as a cancer health disparity in the United States for decades," Lovvorn said, "[It] occurs more commonly in black children of sub-Saharan African ancestry than white children. [While] the survival gap has nearly closed, rates in incidence have not changed. Why is that? What is the biology behind this childhood cancer disparity? That's what we're trying to investigate in our research."
Lovvorn has spent the past 14 years in basic and translational research seeking to identify new treatments of Wilms Tumor for young cancer patients. Through his R21 grant, "Molecular Analysis of Ethnic Variations in WT," Lovvorn is investigating an answer to the driving question of "Are there biological differences between WT of White and Black children in North America?" Lovvorn explained, "Our goal is to identify protein signatures in both groups of patients. If the protein is different from one group to another, perhaps those tumors have activation of various resistant genes to chemotherapies, for example. This is an initial step to personalize therapy and treatment for this disease, beginning with the genetics of one's ethnicity."
Lovvorn targeted Kenyan children for his research because he "wanted a more isolated population that was vulnerable and resource-restrained." He further explained, "It gave us a more focused signature of what a sub-Saharan African WT looks like, and we can see how similar it is in or different from African American children in the States."
Lovvorn's initial research confirmed that there is indeed a cancer health disparity, but his team was surprised. "We found that the most disparate observation occurred between Kenyan black children and American black children, and that protein signatures in Whites fell somewhere in between." Subsequently, Lovvorn completed one of the first "next generation sequencing genomic analysis" of mutations in 10 genes associated with WT development and biology in Kenya specimens – including WT1, IGF2, WTX, CTNNB1, and p53, among others of biologic interest. His findings are now being validated by population geneticists at Vanderbilt.
Lovvorn's research has shown that different ethnic populations of patients have tumors composed of unique proteins that could drive the disparity observed between North American and African children. Further, these unique signatures could represent targets of new, race-specific drugs forming the basis to personalized treatment.
To investigate this disparity further, Lovvorn's current R21 research aims "to explain a pediatric cancer health disparity at the molecular level." He continued, "through the R21 mechanism, we've been able to initiate genomic analysis to try to clarify the ideology of the disparity. NCI has been overly generous to provide funds to support this work. And it creates an opportunity for future studies."
"There's no question that if you don't remove these [Wilms] tumors, kids don't survive. [Treatments] must be multi-modal. We need the therapy, we need the radiation, and we need the surgery all together. But we still have a 15% relapse rate. That's pretty high. When these children relapse, half of them will die."
"The R21 award," Lovvorn said, "has been huge to our research program. It is allowing our team to generate more data to pursue future research, and we hope to pursue an R01 next year. My hope is to move this research to potential drug discovery."
Lovvorn is now in the process of publishing four peer-reviewed manuscripts on the molecular epidemiology of disparities in Wilms tumor, two of which were supported directly from his R21grant. An additional manuscript, also supported by his R21, details risk factors for abandonment of WT care in Kenya, and a fourth will summarize the next generation sequencing of the Kenyan WT and kidney specimens.
Lovvorn received his B.S. degree in Psychology from Duke University and his medical degree from the University of Tennessee. He completed his internship and residency in General Surgery at the Hospital of the University of Pennsylvania in Philadelphia, while holding a Postdoctoral Research Fellowship at the Children's Institute of Surgical Science of the Children's Hospital of Philadelphia. He also has completed a clinical fellowship in Pediatric General and Thoracic Surgery at LeBonheur and St. Jude Children's Hospitals in Memphis. Lovvorn is a Fellow of the American College of Surgeons, Fellow of the American Academy of Pediatrics, and a member of the American Pediatric Surgical Association.
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- Lovvorn HN, et. al.: Race disparities in peptide profiles of North American and Kenyan Wilms tumor specimens. J Am Coll Surg. 2014 Apr; 218(4):707-20.
- Lovvorn HN, et. al.: Wilms tumor survival in Kenya. J Pediatr Surg. 2013 June; 48(6):1254-62.
- Lovvorn HN, et. al.: Molecular characterization of Wilms tumor from a resource-constrained region of sub-Saharan Africa. Int J Cancer. 2012 Sep 15;131(6):E983-94.
- Lovvorn HN, et. al.: Race disparities in Wilms tumor incidence and biology. J Surg Res. 2011 Sep;170(1):112-9.