To study rare cancers, collaboration is key 

In honor of Rare Disease Day on February 28th, we spoke with Professor Stefan Fröhling about his research on rare cancers and his collaboration with Hartwig Medical Foundation. Recently, Hartwig received permission to integrate Fröhling’s rare cancer data into their database. He finds it “particularly frustrating” that there are so few treatment options while rare cancers often affect younger people and expects this collaboration to be mutually beneficial. 

By Laura Nederveen  

Rare cancers are actually not that rare. Together, they account for nearly 25 percent of all cancer cases. A cancer is considered rare if fewer than six new cases occur per 100,000 persons each year. Even within common cancers, such as lung cancer, we nowadays know there are many molecular subtypes, and some of these subtypes can also be considered rare. Due to their rarity, they are less well known, and consequently, fewer treatment options are available. 

This deeply motivates Professor Stefan Fröhling to study rare cancers. Fröhling is Head of the Division of Translational Medical Oncology at the German Cancer Research Center (DKFZ) and Managing Director at the National Center for Tumor Diseases (NCT) in Heidelberg. “Rare cancers receive significantly less research attention compared to common cancers,” he explains. “Consequently, these diseases are less well understood, leading to fewer available treatments, and the prognosis is often considerably worse. Many sarcomas, for example, affect younger people, which makes it particularly frustrating when there are so few treatment options and so many years of life are lost. I believe there is a high unmet medical need.” 

Thanks to advancements in genomics over the past few decades, rare forms of cancer can now be diagnosed with greater precision. But isn’t studying rare diseases very difficult because they are… rare? Fröhling agrees: “Heidelberg has a high-volume cancer center, and much of our research focuses on rare cancers, but locally, we would not generate enough data to study rare diseases. Therefore, we collaborate in several national consortia, such as the German Cancer Consortium (DKTK) and the NCT with its six sites, representing 11 comprehensive cancer centers, as well as a Cancer Core Europe, a consortium involving centers in seven countries, including the Netherlands Cancer Institute (NKI). And now we are starting up this bilateral collaboration with Hartwig Medical Foundation.” 

“Hartwig has built a tumor classifier based on their own data, but their program is more focused on common tumor entities,” Fröhling explains. “Since they would like to increase the number of cases and integrate rare cancers, they asked us to use our data and combine the databases. This permission was recently granted by DKTK and NCT, so we have the green light to continue this collaboration.”  

Conversely, Fröhling and his team are making use of the bioinformatic pipeline developed by Hartwig to analyze genetic tumor data. Fröhling: “What Hartwig does is very advanced. It is really a mutual benefit, and the ‘positive chemistry’ in our interactions, are a big plus. ”Previously, his team has developed their own bioinformatic solutions”, Fröhling says. “It is good what we were doing, but at certain points, Hartwig’s solutions are very attractive. So our bioinformaticians have begun to implement what Hartwig has developed.” 

While using their analysis pipeline, Fröhling has not yet incorporated Hartwig’s data. “But that would be a logical next step,” he says. “Hartwig is combining our data into a huge data pool to determine whether findings from common cancers also apply to rare ones. We could do the same: if our analysis of rare cancers raises a question, we could use this database to see if it is also relevant to more common types. That would be very helpful. I think having a large joint dataset will open up many opportunities for scientific questions and also clinical trials.” 

Rare and common cancer research are closely connected. In some cases, a very rare cancer may turn out to resemble a more common one. Fröhling: “Sometimes, when we study rare cancers, we discover features that have already been observed in common cancers, which can even have clinical implications. For example, if we analyze 30 cases of a rare cancer and find a molecular characteristic typically seen in breast or gastric cancer, it is often unexpected. But because we conducted a comprehensive analysis, we spotted it. In many cases, this allowed us to repurpose, for example, an existing breast cancer drug to treat patients with the rare cancer.” 

One advantage of studying rare cancers is that there are often more opportunities to administer experimental treatments. “In most cases, you cannot simply deviate from standard procedures,” Fröhling explains, “you have to go through several approved treatments before trying something experimental. But for patients with rare cancers, where no standard treatment exists, there is more flexibility to explore new options.” 

In the end, research on rare cancers will help to treat common cancers better, and vice versa. Integrating the two databases will help both fields forward. Fröhling conludes: “I anticipate that this collaboration will improve our understanding of rare and common cancers, including insights that will have tangible clinical implications and, thus, improve outcomes for patients.” 

On 21-22 March 2025 Hartwig Medical Foundation is organizing the first Clinical Cancer Genomics Conference. Professor Fröhling is one of the co-organizers of this international congress, on behalf of DKFZ and NCT.