Solving the complex puzzles of childhood cancer is the challenge for Mass General researcher Miguel Rivera, MD, whose work is supported by Hyundai Hope on Wheels.

A generous $250,000 grant from Hyundai Hope on Wheels is helping Massachusetts General Hospital researcher Miguel Rivera, MD, investigate the complex processes that give rise to Wilms tumor, the most common childhood cancer of the kidney. Ultimately, this work could point the way to better treatments.

Hyundai Hope on Wheels, a nonprofit foundation, funds potentially transformative research on pediatric cancer, a leading cause of death in children.

Hyundai Hope on Wheels, a nonprofit foundation, funds potentially transformative research on pediatric cancer, a leading cause of death in children.

“At Hyundai, we value taking on hard problems and trying to find solutions,” says Zafar Brooks, director of Corporate Social Responsibility and Diversity and Inclusion at Hyundai Motor America. “We are very pleased to lend our resources and give our hands to the fight.”

Wilms tumor typically strikes children ages 1 to 5. Many youngsters with this disease can be cured by surgery to remove the affected kidney followed by chemotherapy. Sadly, 15 percent of children fail to respond to current treatments. And those who are cured are at risk for long-lasting side effects from treatments.

Missteps to Childhood Cancer

Several years ago, Dr. Rivera, an assistant professor of pathology in the Molecular Pathology Unit at Mass General, worked with colleagues to break new ground in pediatric cancer research by discovering the gene WTX. Usually present early in development in master cells called stem cells that help form normal kidneys, WTX is actually missing in 20 percent to 30 percent of Wilms tumors. How deletion of WTX during kidney development leads to tumor formation isn’t yet clear.

Miguel Rivera, MD, receives a handprint from a patient during the Hyundai Hope on Wheels Handprint Ceremony for research on childhood cancer.
Miguel Rivera, MD, receives a handprint from a patient during the Hyundai Hope on Wheels Handprint Ceremony for research on childhood cancer.

With support from the Hyundai Hope on Wheels grant, the Rivera lab is working with a mouse model and directly with Wilms tumor tissue from patients to shed light on the role of WTX. “We can delete WTX directly in kidney stem cells in mice to see what the immediate consequences are and then link these results to pathways that are active in tumors,” Dr. Rivera says.

Further, his team is using an impressive set of next-generation sequencing tools to analyze which genes are “expressed” — that is, switched on and actively doing their jobs — and which genes are turned off in Wilms tumor tissue compared with normal kidney tissue.

Known as epigenomics, this type of research is a remarkably exciting scientific frontier. Learning which gene expression mechanisms work — and which fail to work — in cancer cells versus normal cells could help shape the direction of new targeted therapies that would be less toxic than current treatments.

Powerful Technologies Fuel Research

Epigenomic research demands considerable expertise and technology.

“At MGH, we have a lot of experience sequencing millions of fragments of DNA and analyzing these large data sets to understand what drives cancer cells,” Dr. Rivera says. “I’m motivated by the sad reality of children we cannot treat and excited that now we have powerful technologies that can help us find new ways to fight cancer. Many of the abnormalities that we identify in these studies may also give us insights into how to treat a variety of tumors in children and adults.”

This is the second $250,000 Hyundai Hope on Wheels Scholar grant awarded to Dr. Rivera, who received a 2011 grant for research on pediatric bone cancer. “These grants are absolutely critical for funding new research and new ideas,” Dr. Rivera says.

On Sept. 24, 2016, Hyundai Hope on Wheels awarded another $250,000 Hyundai Scholar grant to Hanno Hock, MD, PhD, a Mass General researcher working on identifying specific gene alterations and mechanisms that help initiate acute lymphoblastic leukemia, a major type of childhood cancer.

All told, MGH scientists have received $950,000 from Hyundai Hope on Wheels in recent years to pursue a range of innovative research on childhood cancers.

All told, MGH scientists have received $950,000 from Hyundai Hope on Wheels in recent years to pursue a range of innovative research on childhood cancers.

“We are extraordinarily pleased to have funded MGH for the work its researchers are doing,” Mr. Brooks says. “These seed funds may result in important papers, new protocols, clinical trials, and indeed, new treatments that help save the lives of children with cancer.”

Mr. Brooks points out that during the past century children often suffered or died from diseases such as polio, whooping cough, measles, mumps and rubella. “We believe that by working with the scientific community, it is possible to turn pediatric cancer into a curable disease,” he says.

To learn more about pediatric cancer research or to make a donation, please contact us.

Hyundai Hope On Wheels is a nonprofit organization that is committed to finding a cure for childhood cancer. Launched in 1998, Hyundai Hope On Wheels provides grants to eligible institutions nationwide that are pursuing life-saving research and innovative treatments for the disease. HHOW is one of the largest nonprofit funders of pediatric cancer research in the country, and primary funding for Hyundai Hope On Wheels comes from Hyundai Motor America and its more than 830 U.S. dealers. Since its inception, Hyundai Hope On Wheels has awarded more than $115 million towards childhood cancer research in pursuit of a cure.

To learn more about Hyundai Hope On Wheels, please visit its website, or follow on social media at FacebookTwitter and YouTube.