Key takeaways
- ROS1-positive non-small cell lung cancer (NSCLC) is a rare lung cancer subtype occurring when part of the ROS1 gene fuses with another gene. Affecting around 1% to 2% of people with NSCLC, it tends to occur in younger people, females, and those who have never smoked or smoked lightly.
- Experts use various methods for diagnosis, including imaging plus biopsy or a blood-based ‘liquid biopsy.’ Biomarker testing helps identify ROS1 rearrangements, which can guide treatment with ROS1 inhibitors such as 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.
The ROS1 (c-ROS proto-oncogene 1) gene is a gene essential for cell growth and signaling. It is a cell-surface receptor that plays an important role in regulating typical 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 type of lung cancer that often spreads quickly.
ROS1-positive lung cancer means that the ROS1 gene has fused with a nearby gene, leading to irregular cell growth. This causes cancer cells to grow more rapidly.
- NSCLC
- glioblastoma multiforme (a type of brain cancer)
- bile duct cancer
- ovarian cancer
- stomach cancer
- colon cancer
- rectal cancer
Your healthcare team will work to understand whether a cancer is ROS1-positive, as this can help inform a treatment plan.
The average age when receiving a ROS1-positive NSCLC diagnosis is generally 45 to 50 years. This age group is younger than that of people with other types of NSCLC.
The condition seems to be predominant in females, people of Asian heritage, and in those who have never smoked or only smoked a small amount.
Symptoms of ROS1-positive NSCLC are similar to those seen in other lung cancer types.
However, you may not notice any symptoms until the condition has progressed.
Some lung cancer symptoms include:
- persistent or worsening cough
- wheezing when breathing
- rust-colored phlegm or phlegm that contains blood
- chest pain that becomes worse when coughing, laughing, or taking a deep breath
- a scratchy or raspy throat
- loss of appetite and unexplained weight loss
- feeling short of breath, tired, and weak
- recurring bronchitis, pneumonia, or other infections
A ROS1-positive lung cancer diagnosis involves certain tests, such as:
- tumor tissue testing
- blood testing
- biomarker testing
Your doctor may perform fluorescence in situ hybridization (FISH), which involves examining tissue under a microscope to detect chromosomal changes.
They may also suggest next-generation sequencing (NGS), which is also known as comprehensive biomarker testing. In NGS testing, your doctor will place tumor tissue into a machine that analyzes many different potential biomarkers.
If you are unable to have an NGS test, you may have a liquid biopsy instead — a test that can detect specific biomarkers in the blood.
Your medical team may perform several of these tests to help confirm a diagnosis.
Biomarker testing is important. It involves lab tests that
- specific genes
- proteins
- hormones
- other substances
Biomarker testing can be precise, whether it targets a single biomarker or a panel of multiple biomarkers.
The biomarker tests that doctors perform will depend on the type of cancer they are investigating.
Once they have identified the cancer, they may request a companion diagnostic test, which is a biomarker test used to inform drug treatment decisions.
Biomarker testing is typically one of the first tests a healthcare team considers when investigating ROS1-positive NSCLC.
If you are concerned about symptoms that may be related to NSCLC, you should speak with a doctor as soon as possible. The sooner investigations begin, the sooner your team than give or rule out a diagnosis.
The treatment for ROS1-positive NSCLC varies from person to person and depends on the type of ROS1 rearrangement and whether the cancer has spread.
The initial treatment for an advanced-stage ROS1-positive lung cancer may include ROS1 tyrosine kinase inhibitors (TKI) or ROS1 inhibitors.
The current
- ceritinib (Zykadia)
- crizotinib (Xalkori)
- entrectinib (Rozlytrek)
Lorlatinib (Lorbrena) is another medication that you may be prescribed if you have ROS1-mutated advanced NSCLC. People who receive this medication have typically already received treatment with entrectinib, crizotinib, or ceritinib.
Repotrectinib (Augtyro) and taletrectinib (Ibtrozi) may also be treatment options for those with ROS1-mutated advanced NSCLC. You may or may not have already received treatment with entrectinib, crizotinib, or ceritinib.
Over time, cancer cells can change, and you may develop resistance to medications. In these instances, a doctor may recommend a tissue or liquid biopsy. Depending on the results, they may recommend switching to another ROS1-inhibitor or enrolling in a clinical trial.
Doctors may also recommend off-label targeted therapy. Off-label means the
There are similarities and differences between ROS1-positive NSCLC and epidermal growth factor receptor (EGFR)-positive lung cancer.
The table below provides more detail on these.
| 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 • nonsmokers • light smokers • females | • nonsmokers • 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) |
The main difference is how the gene behaves. One is a gene rearrangement, and the other is a mutation. Treatments also differ, and EGFR-positive NSCLC is more common.
The treatments for ROS1-positive NSCLC continue to evolve, with newer medications overcoming treatment resistance and offering new hope for disease management.
A 2025 real-world study 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 when treatment resistance occurs, and the development of 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.
The condition occurs when a portion of the ROS-1 gene fuses with another gene, leading to abnormal cell growth and cancer development.
While symptoms of ROS1-positive NSCLC may not appear until the condition has advanced, treatment options are available.
You should consider speaking with your healthcare team as soon as possible if you are concerned about your lung health and lung cancer risk.