Study Reveals New Treatment Pathways for Rare Head and Neck Cancer

Deformities in the hands and arms, serious heart and kidney problems, repeated infections, and excessive or unusual bleeding are just some of the health issues people with an extremely rare genetic disorder called Fanconi anemia (FA) may face. The good news is that treatment of this condition has vastly improved, helping people with FA live longer and better manage their health.

But that progress comes with a significant catch: People with FA have a very high risk of being diagnosed with cancer, especially cancers that form in the head and neck regions. And these cancers “are extremely difficult to treat,” explained Agata Smogorzewska, MD, PhD, of The Rockefeller University in New York. “They develop very quickly … and the tumors are very aggressive.”

Now, a new a study—co-led by Dr. Smogorzewska, along with Jennifer Grandis, MD, and Daniel Johnson, PhD, from the University of California San Francisco—has shown that some existing and widely used cancer drugs may be effective options for people with FA diagnosed with these cancers. In the study, so-called targeted therapies that are standard treatments for cancers like lung and breast shrank tumors in advanced mouse “models” of FA-related head and neck cancers.

The study was supported by Stand Up To Cancer and several partner organizations, including the Fanconi Cancer Foundation, the Farrah Fawcett Foundation, the American Head and Neck Society, and the Head and Neck Cancer Alliance.

Fanconi anemia-related cancers are difficult to “model” in mice, but the team was able to collect samples from tumors of people with FA-related head and neck cancers and successfully grow them in mice, which are known as “patient-derived xenografts” or PDXs.

Studies in any type of cancer model rarely affect patient treatment. However, because FA-related head and neck cancers are so rare, this study may be an exception, Dr. Smogorzewska said.

“Absolutely,” she said, when asked if these findings should potentially affect how people with these cancers are treated. The study showed that “each patient’s tumor is quite different,” she said. “It tells us that … we need to understand each tumor separately and identify the specific therapies most likely to work against them.”

DNA repair shortcomings lead to high cancer risk

In the United States, fewer than 35 people a year are diagnosed with FA, typically children and adolescents. Thanks to advances in bone marrow transplants, many people with FA now live far longer than was once possible.

That increased lifespan, however, has created its own conundrum. Fanconi anemia is caused by a breakdown in cells’ ability to repair damage to their DNA. It’s this same faulty DNA repair system that can, and very often does, cause cancer, with head and neck cancers now being the most frequent.

Treating this cancer in people with FA is complicated. Surgery is the primary treatment. But if the tumor can’t be removed entirely with surgery or if it comes back after surgery, options are very limited.

For example, because it works by damaging DNA in cells, the standard chemotherapy used to treat head and neck cancer isn’t an option. And although radiation can be effective, the safest approaches to using it in people with FA are still evolving and unfamiliar to most oncologists.

And, finally, because FA is so rare—a person is about 10 times more likely to be struck by lightning in their lifetime than have FA—it’s extremely difficult to conduct the kinds of research, including clinical trials, that are commonplace for most cancers.

Model establishes a path for personalized treatment

This new study represents the first published report of a successfully created PDX model of FA-related head and neck cancer. Although developing these models was an important accomplishment, it was the findings from the comprehensive tumor analyses and treatment-related experiments the models made possible that really got the team excited.

First, they showed that the tumors, when grown in mice, still had the same genetic mutations that were present in the original tumors. More importantly, when they treated animals with cancer drugs that work against tumors with specific cancer-fueling mutations, the treatments worked remarkably well, slowing tumor growth.

And although these so-called targeted therapies worked well on their own, certain combinations of these drugs were even more effective. From a treatment perspective, combinations of targeted therapies “seems to be better and potentially the way to go in this complex disease,” Dr. Smogorzewska said.

Potential impact on patient care

In nearly all instances, a study conducted in mice—even one with such robust results—would not be enough to change the treatment of humans with cancer. But given the extremely limited treatment choices for these extremely rare patients, exceptions to the usual practices may be a strong consideration, the research team believes.

One way of doing so could be to employ a special type of single-patient study, clearance for which must be given by the FDA, that is often used for people with extremely rare diseases.

Consideration of these “N of 1” studies, as they’re often called, is “100% an option” for patients with FA-related head and neck cancers that have come back after surgery, Dr. Smogorzewska said.