ROS1 positive cancer, or ROS1+ cancer, is any cancer that tests positive for a fusion in the ROS1 gene. It is sometimes called ROS1 fusion or ROS1-rearranged cancer. ROS1+ cancer occurs in 1-2% of non-small cell lung cancers (NSCLC), and has also been found in glioblastoma, angiosarcoma, melanoma, and choloangiosarcoma, as well as colorectal, gastric, and ovarian cancers.
ROS1+ cancer occurs when a gene called ROS1 fuses with a nearby gene and swaps pieces of DNA. Thus far over 20 different genes have been found to fuse with ROS1 and drive ROS1+ cancer. When this happens, the ROS protein encoded by the ROS1 gene becomes abnormal. The actions of this abnormal protein drive the cell to behave like cancer: live forever, make many copies of itself, invade neighboring cells, and ultimately travel through the bloodstream and lymph to create tumors in other parts of the body.
ROS1 cancer tends to be aggressive, and can spread to the bones and brain.
Identifying ROS1+ Cancer
ROS1 cancer has been most studied in NSCLC. NSCLC patients who have ROS1+ lung cancer tend to be younger than average, and usually test negative for other known lung cancer gene mutations like EGFR, KRAS and ALK. According to the National Comprehensive Cancer Network treatment guidelines for NSCLC, testing NSCLC patients for ROS1+ cancer is standard of care in the USA; however, some primary care doctors and general oncologists might not be aware of this. The fusion can be detected using FISH molecular testing (the gold standard), a genomic panel like Foundation One, or immunohistochemistry (IHC), but the accuracy of these tests can vary. Doctors might not consider ROS1+ testing for NSCLC patients living in countries that do not have an approved drug for ROS1+ cancer, or for patients who have types of cancer other than NSCLC.
Treating ROS1+ Cancer
Drugs that target the mutated ROS1 protein are called targeted therapy drugs. They are also called tyrosine kinase inhibitors, or TKIs, because the ROS1 protein belongs to the tyrosine kinase family, and the drug is inhibiting that protein. TKIs can be more effective than chemo for many ROS1+ lung cancer patients–chemo is typically effective for 20% of patients, whereas crizotinib (a TKI approved in the USA and some other countries for ROS1+ cancer) is effective for 70-80% of lung cancer patients. Some patients experience stability or no evidence of disease (NED) for years, but for most patients, the cancer eventually starts growing again. Unfortunately, TKIs are not a cure–they only inhibit the cancer, not kill it. Eventually the cancer mutates and patient develops a resistance mutation that makes the TKI ineffective.
ROS1 patients are likely to develop cancer metastases in the brain. Some ROS1 TKIs (like ceretinib, lorlatinib, and entrectinib) treat the brain effectively, but others (like crizotinib) do not. If a ROS1 patient develops brain mets while the cancer in the rest of the body is well-controlled, their doctor may consider switching the patient to a TKI that does treat the brain, or remaining on the current TKI and treating the brain with stereotactic radiosurgery (SRS) like Gamma Knife (which allows the patient to stay on the TKI longer).
Detailed Information about ROS1 gene and fusions
- My Cancer Genome: ROS1 Fusions in Non-Small Cell Lung Cancer
- National Center for Biotechnology Information: ROS proto-oncogene 1 , receptor tyrosine kinase [Homo sapiens (human)]
Last updated 07-Nov-2020