Pheochromocytoma is a rare tumor with an incidence of 3-8 cases per million population per year. The research published highlights the largest study on this cancers' molecular causes and focuses on patients with metastatic pheochromocytomas, which account for 20 percent of all cases. Survival of patients with metastatic pheochromocytoma is 20-60 percent at 5 years.

CNIO researchers Bruna Calsina, PhD, (left) and Mercedes Robledo, PhD, both at the Spanish National Cancer Research Center, focus on the molecular causes of metastatic pheochromocytomas. CNIO researchers Bruna Calsina, PhD, (left) and Mercedes Robledo, PhD, both at the Spanish National Cancer Research Center, focus on the molecular causes of metastatic pheochromocytomas.

Mercedes Robledo, PhD, Head of the Hereditary Endocrine Cancer Group at the Spanish National Cancer Research Center (CNIO) and one of the two researchers who led the study, has been studying these tumors since 1996.

"One of the difficulties of working with rare diseases is to recruit large series of patients to reach robust conclusions," she noted. "This study stands out because the number of samples we worked with was outstanding." The CNIO belongs to the Spanish network of Rare Diseases (CIBERER).

To understand the magnitude of the study, CNIO researcher and co-author Bruna Calsina, PhD, explained, "The number of patients with metastatic disease that our study gathers corresponds to a population of 100 million people." This has been possible thanks to the collaboration between 16 centers from six countries around the world, with which the CNIO has been collaborating for the last decade.

Such a large sample was necessary to achieve what they and their research colleagues have achieved with their work: to identify, at the time of diagnosis of the primary tumor, markers associated with an increased risk of metastasis. These markers can be added to other clinical and histological criteria for personalized clinical management.

As Robledo and Calsina explained, most patients with this type of tumor who develop metastasis do so 1 or 2 years after the diagnosis of the disease, but there are cases in which metastasis develops 10 or 20 years after the initial diagnosis. The new molecular markers will help clinicians to follow more closely those patients at high risk of metastasis.

Another problem with this rare disease is that the therapies do not always work, and the reason is unknown. "This is a hereditary disease in 40-50 percent of cases," explained Robledo, "and very complex from a genetic point of view. Up to 22 genes related to the disease have been identified, of which five have been discovered in our laboratory."

The more genes involved in a disease, the more difficult it is to study and the more complex it is to find effective therapies. To date, several types of treatment have been tested, from chemotherapy to targeted therapies, but as Calsina stated, "It is not known a priori which patients might respond to one therapy or another."

For this reason, another part of the research consisted of searching for markers that would allow treatment to be personalized. The research led by Robledo and Calsina has identified a group of patients with pheochromocytoma who could benefit from immunotherapy treatments.

"The study will be a benchmark in the field of metastatic pheochromocytoma," Robledo concluded.