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The Consequences of Curing Childhood Cancer

The majority of American children with cancer will be cured, but it may leave them unable to have children of their own. Should preserving fertility in cancer survivors be a research priority?
(Photo: DVARG/Shutterstock)

(Photo: DVARG/Shutterstock)

This story starts with good news: Children who get cancer are increasingly likely to survive. Roughly 16,000 U.S. children will be diagnosed with cancer in 2014, according to American Cancer Society estimates, and the vast majority of them will beat their disease. The overall five-year survival rate for pediatric cancer has gone up from 50 percent in 1975 to 80 percent today, and survival rates for some common childhood cancers go as high as 90 percent. As a result, there are roughly 400,000 survivors of childhood cancer living in the U.S. today. Most children who get cancer will now grow up to live healthy adult lives.

That's the good news. The bad news is that cancer treatments often leave these young survivors unable to make a big life decision that is important to many adults: to choose whether or not to have children. Cancer drugs, designed to kill rapidly reproducing tumor cells, also take down healthy cells that replicate quickly. The off-target casualties include keratinocytes in hair follicles, which cause patients to lose their hair, and the germline stem cells in the testes and ovaries that are the crucial precursors of sperm and eggs, which leave patients infertile.

Cancer patients who are at risk for losing their fertility are typically given a chance to do something about it before starting treatment. For older teens and adults, the solution is relatively simple: Bank sperm or eggs, which can be used later in routine fertility procedures like in vitro fertilization. This is clearly not an option for younger patients. In fact, there are currently no good options for preserving the fertility of younger patients. An important life decision is taken away from them before they are old enough to make it, and the psychological consequences can last a long time.

Fertility research meets a growing need in our society as people choose to have children later in life, when fertility problems are more likely, and it addresses an important source of long-term psychological distress in the growing number of cancer survivors.

Cancer patients who haven’t reached puberty don’t have mature gametes to save, but they do have those crucial germline stem cells. Before their cancer treatment, younger patients could bank a sample of germline stem cells. Later in life, those cells can be transplanted back into the patient, where they will develop into viable sperm or eggs. The logic is similar to that of several experimental or hoped-for stem-cell transplant therapies that are being studied for a variety of diseases. The catch is that, like most stem cell therapies, it doesn't work yet.

Or rather, like so many potential medical treatments, it only works well in mice. But University of Pittsburgh scientist Kyle Orwig is optimistic about the prospects for male cancer survivors. Earlier this year, Orwig and his colleagues wrote that "it is reasonable to expect in the next decade that the options to preserve and restore male fertility ... [will] include stem cell transplantation, tissue grafting, and/or culture to produce fertilization competent gametes."

Germline stem cell transplants may work within the next decade, but the results of the technology sound like science fiction. In 2012, Orwig's research team successfully performed what basically amounts to a sperm transplant. They transferred germline stem cells from the testes of one monkey into the testes of another. The result was a monkey that made fertile sperm carrying the DNA of the other animal.

The technology has since been pushed even further. In a recent study, Orwig's group, together with a Stanford University team led by Renee Reijo Pera, created germline stem cells from skin cells. They collected the skin cells from donor men, and converted them into what's called an induced stem cell. The researchers then transplanted those induced stem cells into mouse testes, where they became functional germline stem cells.

The researchers didn’t quite produce mice that make human sperm—for unknown reasons, human germline stem cells don't completely mature into fertile sperm in mouse testes. But experiments like this one let researchers study how germline stem cells work, and what happens when things go wrong.

This research, along with parallel efforts to develop the best way to store and thaw frozen germline tissue brings the technology closer to being a clinic-ready therapy. Many young cancer patients are already banking tissue samples in the hope that it will work.

But research on this fertility-restoring technology raises a few questions. Will it work for girls? Should this really be a biomedical research priority? And won't cancer survivors pass on a risk for disease to their children?

A key difference between men and women—germline cells generate millions of gametes per day in men, but not in women—means that germline stem-cell transplants for girls follow an independent line of research. Still, researchers are pursuing treatments for women, and, unlike the male version of the therapy, it may already have led to successful pregnancies.

Should preserving fertility in cancer survivors be a research priority, though? The investment in this research is, in fact, small compared to the resources that go into studies of major killers like heart disease and cancer. Also, fertility research meets a growing need in our society as people choose to have children later in life, when fertility problems are more likely, and it addresses an important source of long-term psychological distress in the growing number of cancer survivors.

And finally, are cancer survivors likely to pass on a risk for disease to their children? With the exception of certain inherited cancers, the answer appears to be “No.” Cancer in anyone under 40 is surprising, especially in children, as it typically takes the better part of a lifetime to accumulate the mutations that lead to cancer. Why cancer happens in young people is still poorly understood, and so genetic counseling is important for cancer survivors who choose to have children. But right now, there is no reason to think that most cancer survivors who decide to have children are making a genetically risky choice.

Preserving the fertility of young cancer survivors is a problem that can be solved. It's a chance to use a relatively inexpensive and minimally invasive technology to make these survivors' lives better.