First ROS1 Fusion in Peritoneal Mesothelioma Responds to Crizotinib

Oncologists at Changzhou Cancer Hospital in China have published what they describe as the first case of malignant peritoneal mesothelioma carrying a TFG-ROS1 gene fusion, a molecular target already well established in lung cancer treatment. The patient, a 56-year-old woman with no known asbestos exposure, achieved six months of progression-free survival on crizotinib after immunotherapy failed.

The case report, published in Frontiers in Oncology, adds peritoneal mesothelioma to the short list of cancers where ROS1 fusions have been found, and raises new questions about how molecular profiling could change treatment for people with this rare disease.

What the Case Shows

Peritoneal mesothelioma accounts for roughly 7% to 20% of all mesothelioma diagnoses and is far less studied than the pleural form of the disease. Standard chemotherapy remains the primary treatment, but outcomes are poor and options are limited.

In this case, next-generation sequencing identified a TFG-ROS1 rearrangement in the tumor, a type of gene fusion that had never been reported in peritoneal mesothelioma. ROS1 fusions are rare across all cancers but are an established treatment target in non-small cell lung cancer, where crizotinib and other ROS1 inhibitors have shown meaningful response rates.

When the patient’s disease progressed after immunotherapy, her clinical team started crizotinib based on the molecular finding. She achieved six months of disease control before progression.

Resistance and Next Steps

After the disease progressed on crizotinib, the research team identified an acquired resistance mutation, ROS1 p.K1991N. Based on what is known about resistance patterns in lung cancer, the authors suggest entrectinib, a next-generation ROS1 inhibitor, could overcome this specific mutation.

The finding follows a pattern familiar in precision oncology: targeted therapy works, resistance develops through a specific mechanism, and a second drug addresses that mechanism. The cycle has extended survival in other cancers for years.

Why Molecular Testing Matters in Rare Cancers

The most commonly mutated genes in peritoneal mesothelioma are BAP1 (found in roughly 48% of cases), NF2, CDKN2A, and PBRM1. Gene fusions are extremely rare. Only a handful of ALK rearrangements and EWSR1/FUS-ATF1 fusions have been reported, mostly in younger patients.

This case adds ROS1 to that list and raises a practical question for people diagnosed with peritoneal mesothelioma: is molecular testing part of the standard workup?

For many, it is not. The authors argue that broader genomic profiling could identify treatable targets in a disease that currently has few options beyond first-line chemotherapy. They write that “lessons learned from other solid tumors” can inform treatment strategies for rare diseases like peritoneal mesothelioma.

The Broader Picture

The case is notable for another reason: the patient had no documented asbestos exposure. While asbestos remains the primary cause of mesothelioma, a minority of cases occur without any known exposure history. Peritoneal mesothelioma, in particular, has a higher proportion of cases in women and younger adults compared to the pleural form.

Researchers have increasingly focused on BAP1 and other inherited genetic factors that may predispose certain people to mesothelioma without occupational asbestos contact. Whether ROS1 fusions represent a similar non-asbestos pathway remains unknown, but the authors call for further investigation.