Findings on pheochromocytoma, a rare cancer

Pheochromocytoma is a rare tumor, with an incidence of three to eight cases per million inhabitants each year.

The largest genomic study of pheochromocytoma to date identifies patients at highest risk of metastasis and those who would respond to immunotherapy.

The study is the work of a team led by a group from the National Cancer Research Center (CNIO), which is a world reference in this rare cancer.

The new study is the largest to date on the molecular causes of this cancer.

The work focuses on those patients with metastatic pheochromocytomas, which represent 20% of all cases. Survival of patients with metastatic pheochromocytoma is 20% to 60% at five years.

One of the two researchers who have led the work is Mercedes Robledo, head of the Hereditary Endocrine Cancer Group at the CNIO, which is part of the Center for Biomedical Research in the Network for Rare Diseases (CIBERER) in Spain. Robledo has been dedicated to the study of these tumors since 1996: “One of the difficulties of working with rare diseases is recruiting large series of patients that allow robust conclusions to be reached. And this study stands out because the number of samples with which we have worked is exceptional”.

To understand the magnitude of the study, the co-author and CNIO researcher Bruna Calsina explains: “The number of patients with metastatic disease in our study corresponds to a population of one hundred million people.”

This has been possible thanks to the collaboration between 16 reference centers for the study of the disease from six countries around the world, with which the CNIO Group has been working for the last decade.

The researchers Bruna Calsina (left) and Mercedes Robledo, from the CNIO. (Photo: Laura M. Lombardy, CNIO. CC BY)

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 a greater risk of metastasis. These markers may be added to other clinical and histological criteria for personalized clinical management.

As Robledo and Calsina explain, the majority of patients with this type of tumor who develop metastases do so one or two years after the diagnosis of the disease, but there are cases in which the metastasis develops after ten or twenty years from the initial diagnosis. The new molecular markers will help responsible physicians to monitor patients at high risk of metastasis more closely.

Another problem with this rare disease is that therapies don’t always work, and the reason is unknown. “This is a hereditary disease in 40%-50% of cases -explains Mercedes Robledo-, and very complex from a genetic point of view. Up to 22 genes related to the disease have been identified, of which 5 have been discovered in our laboratory”.

The more genes are involved in a disease, the more difficult it is to study and the more complex it is to find effective therapies. To date, various types of treatments have been tried, from chemotherapy to targeted therapies, but as Bruna Calsina explains, “it is not known a priori which patients could respond to one therapy or another.”

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

The study is titled “Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma”. And it has been published in the academic journal Nature Communications. (Source: CNIO)