Key takeaways
- ROS1-positive non-small cell lung cancer (NSCLC) is a rare subtype of lung cancer that occurs when part of the ROS1 gene fuses with another gene. It affects about 1% to 2% of people with NSCLC and tends to occur in younger individuals, females, and people who have never smoked or smoked lightly.
- Diagnosis uses imaging plus biopsy or a blood-based “liquid biopsy,” and treatment may include surgery, targeted therapy, chemotherapy, or immunotherapy, depending on the cancer stage and treatment goals. Biomarker testing helps identify ROS1 rearrangements and guide treatment with ROS1 inhibitors like crizotinib (Xalkori), entrectinib (Rozlytrek), or repotrectinib (Augtyro).
- Research suggests that people who receive crizotinib as first-line treatment may have an average progression-free survival of 18.3 months compared with 3.7 months for chemotherapy. Newer medications are overcoming treatment resistance, offering hope for improved disease management.
ROS1 (c-ROS proto-oncogene 1) is a gene that is essential for cell growth and signaling. It is a cell-surface receptor that has been shown to play an important role in regulating specific cellular processes and in the growth and progression of many cancer types, including lung cancer.
Sometimes, a section of ROS1 can break off and fuse with another gene, a process sometimes called rearrangement. ROS1 gene rearrangements occur in roughly 1% to 2% of people with non-small cell lung cancer (NSCLC).
ROS1-positive NSCLC is an aggressive lung cancer type that usually spreads quickly.
ROS1-positive lung cancer means that the ROS1 gene has fused with a nearby gene, leading to irregular cell growth and causing any cancer cells to grow more rapidly.
- NSCLC
- glioblastoma multiforme, which is a type of brain cancer
- bile duct cancer
- ovarian cancer
- stomach cancer
- colon cancer
- rectal cancer
Understanding whether a cancer is ROS1-positive can help inform a treatment plan.
The average age at diagnosis of ROS1-positive NSCLC is around 45 to 50 years, which is younger than that of people with other NSCLC types.
There seems to also be a predominance in females, people of Asian heritage, and people who have never smoked or smoked lightly.
Symptoms of ROS1-positive NSCLC are similar to those of other lung cancer types, and a person may not notice any symptoms until the condition has progressed.
Some lung cancer symptoms include:
- persistent or worsening cough
- wheezing
- rust-colored phlegm or phlegm containing blood
- chest pain that may worsen when breathing deeply, coughing, or laughing
- having a scratchy or raspy throat
- loss of appetite
- unexplained weight loss
- feeling short of breath
- feeling tired or weak
- infections such as recurring bronchitis and pneumonia
ROS1-positive lung cancer testing involves:
- tumor tissue testing
- blood testing
- biomarker testing
Fluorescence in situ hybridization (FISH) analysis is one test a doctor may perform. The test involves looking at tissue under a microscope to detect chromosomal changes.
They may also recommend next-generation sequencing (NGS), also known as comprehensive biomarker testing. In NGS testing, doctors place tumor tissue into a machine that simultaneously analyzes many potential biomarkers.
If a person is unable to have an NGS test, they may have a liquid biopsy instead. A liquid biopsy can detect specific biomarkers in the blood.
A person’s medical team may order several of these tests simultaneously to help confirm the diagnosis.
Biomarker testing for cancer involves lab tests that can
- specific genes
- proteins
- hormones
- other substances
Biomarker testing can be precise. It can look for a single biomarker or a panel of multiple biomarkers. Which biomarker tests a medical team selects depends on a person’s cancer type.
Once a person’s healthcare team identifies the cancer type, they may request a companion diagnostic test, a biomarker test used to inform drug therapy decisions.
Biomarker testing should be among the first steps a healthcare team considers when investigating ROS1-positive NSCLC.
If an individual has concerns about symptoms that may be related to NSCLC, they should speak with a doctor as soon as possible. The sooner the medical team makes — or rules out — a diagnosis, the better the likely outcome.
Treatment for ROS1-positive NSCLC varies from person to person and depends on factors such as the type of ROS1 rearrangement and whether the cancer has spread.
Initial treatment for advanced-stage ROS1-positive lung cancer may include a ROS1 tyrosine kinase inhibitor (TKI) or ROS1 inhibitor.
Currently,
- ceritinib (Zykadia)
- crizotinib (Xalkori)
- entrectinib (Rozlytrek)
Lorlatinib (Lorbrena) may be a treatment option for those with a ROS1-mutated advanced NSCLC. They will typically already have received treatment with entrectinib, crizotinib, or ceritinib.
Repotrectinib (Augtyro) and taletrectinib (Ibtrozi) may also be treatment options for those with ROS1-mutated advanced NSCLC. A person may already have received treatment with entrectinib, crizotinib, or ceritinib, but they may not have.
Over time, an individual’s cancer may change or develop resistance to medication. In these instances, a doctor may recommend a tissue or liquid biopsy to investigate further. They may then recommend switching to another ROS1-inhibitor or enrolling in a clinical trial.
They may also recommend off-label targeted therapy. Off-label means the
There are similarities between ROS1-positive NSCLC and epidermal growth factor receptor (EGFR)-positive lung cancer, but also differences.
Let’s look at them in the table below.
| ROS1-positive | EGFR-positive | |
|---|---|---|
| Prevalence | rare (1% to 2% of NSCLC cases) | more common (around 10% to 15% of NSCLC in Western populations and up to 50% in Asian populations) |
| Who is most commonly affected? | • people ages 45 to 50 • non-smokers • light smokers • females | • non-smokers • females • Eastern Asian populations |
| How it affects the body | gene rearrangement, as ROS1 fuses to another gene | gene mutation, most often Exon 19 deletions or L858R point mutations |
| First line therapies | • entrectinib (Rozlytrek) • crizotinib (Xalkori) • repotrectinib (Augtyro) • taletrectinib (Ibtrozi) | • osimertinib (Tagrisso) • erlotinib (Tarceva) • gefitinib (Iressa) • dacomitinib (Vizimpro) |
Treatments for ROS1-positive NSCLC are ever-evolving, with newer medications overcoming treatment-resistant disease. These treatments provide new hope for disease control and management.
In one 2025 real-world study, evidence suggested that those who chose crizotinib as their first-line treatment had an average progression-free survival of 18.3 months, compared with those who received chemotherapy, who had an average progression-free survival of 3.7 months.
Advancements in biomarker testing, retesting if treatment resistance occurs, and the development of newer treatment options should all lead to more favorable outcomes in the future.
ROS1-positive NSCLC is a rare form of lung cancer that mainly affects non- or light smokers. It occurs when a portion of the ROS-1 gene fuses with another gene, leading to abnormal cell growth and cancer development.
While symptoms of the condition may not appear until it has advanced, treatment options are available.
A person should consider speaking with their healthcare team as soon as possible if they are concerned about their lung health and risk of lung cancer.