What Is ROS1-Positive Lung Cancer?

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ROS1 positive lung cancer is an aggressive form of lung cancer that often spreads quickly. New, targeted medications can help keep this type of lung cancer from progressing for a period of time, providing a better prognosis today compared to previous generations.

A ROS1 rearrangement is a type of chromosome abnormality that may affect cells of non-small cell lung cancer (NSCLC). This genetic mutation occurs in about 1% to 2% of people diagnosed with NSCLC.

Symptoms of ROS1-Positive Lung Cancer

ROS1 mutation is most often seen in adenocarcinoma tumors that are negative for other driver mutations. Adenocarcinoma, the most common type of NSCLC, usually begins near the outer portion of the lungs and typically does not produce symptoms in the early stages.

When adenocarcinoma progresses to the point that tumors interfere with breathing, signs are often less obvious than with other forms of lung cancer, but may include:

Because these signs usually begin only after the cancer has spread, adenocarcinoma and ROS1 variations of adenocarcinoma are usually diagnosed at an advanced stage of cancer.


Cell genes act as a blueprint for proteins that regulate the growth and division of cells. When one of these genes is damaged, mutated, or rearranged, it directs the production of an abnormal protein, which may then function abnormally.

The ROS1 gene is one in a subfamily of tyrosine-kinase insulin-receptor genes. The ROS1 gene mutation seen in NSCLC is really a fusion between ROS1 and another gene. This fusion produces a defective gene that acts as a chance driver, causing cancer cells to multiply excessively.

Mutations like the ROS1 rearrangement are often acquired, which means that they are not inherited or present at birth.

Studies have found that certain factors are associated with ROS1-positive lung cancer:

  • Age: The median age of people with ROS1 rearrangements is estimated to be 50.5. (The median age for lung cancer, in general, is 72.)
  • Sex: ROS1 seems to be more common in women, with 64.5% of occurrences in females in one study. (Lung cancer, in general, is more common in men.)
  • Smoking history: A greater percentage—an estimated 67.7%—are never-smokers. (Smokers are at greater risk for lung cancer overall.)


There are a few ways in which people with lung cancer can be tested to see if they have a ROS1 rearrangement. This genetic defect is only present in the cancer cells, and not in any other cells in the body.

Genetic testing is usually done on a tissue sample from a lung biopsy or from tissue removed during lung cancer surgery. Increasingly, healthcare providers are using liquid biopsy to help diagnose ROS1 rearrangement. This blood test checks for cancer cells circulating in the blood and can be used to identify genetic mutations in cancer cells.

Testing methods include using immunohistochemistry and fluorescence in situ hybridization (FISH) to analyze the samples and determine genetic abnormalities.

Part of the testing involves ruling out other genetic abnormalities including KRAS mutationsEGFR mutations, and ALK rearrangements. If none of these mutations is found, the cancer is referred to as triple-negative NSCLC. (Note: This is completely different than triple negative breast cancer).

Testing will also help identify the stage of your lung cancer, which is important for determining the best course of treatment for your particular type of NSCLC.


If your lung cancer is caught in the early stages—1, 2 or 3A—local treatments may be recommended. These include treatments that work on cancer tumors that are still small and located in one place. They include:

  • Surgery: Options may include removing some lung tissue, a wedge-shaped piece of lung, a lobe of one lung, or an entire lung.
  • Radiation: High-energy radiation is aimed at tumors to kill cancer cells and eliminate or shrink tumors.

For more advanced cancer or tumors that are inoperable or not able to be irradiated, chemotherapy has been the standard treatment of decades.

Chemotherapy drugs, which kill cancer cells but also damage healthy cells, are still widely used for lung cancer, but with ROS1 rearrangement, these drugs may not be the first course of treatment. Instead, healthcare providers are now using targeted medications, which offer many advantages.

Some chemotherapy agents are also effective in ROS1-positive tumors. ROS1-positive lung cancer appears to respond well to the chemotherapy drug Alimta (pemetrexed), for instance.

Targeted Treatment

Targeted therapy medications are oral medications that act on specific genetic mutations to prevent cancer from growing, shrink tumors, or manage cancer symptoms.

Currently, two oral medications have U.S. Food and Drug Administration (FDA) approval for patients with metastatic NSCLC who have ROS1-positive lung cancer:

  • Rozlytrek (entrectinib)—600 milligrams (mg) taken once daily
  • Xalkori (crizotinib)—250 mg taken twice daily

Both are meant to be taken long term. You would only stop taking the medications if the cancer starts to spread (which indicates the drug is no longer working) or if you cannot tolerate the medication. Never stop any medication without first consulting your healthcare provider.

Zykadia (ceritinib), a kinase inhibitor indicated for the treatment of ALK-positive (NSCLC), has also been used to treat ROS1-positive lung cancer.

Studies suggest that a component of vitamin E called a-tocopherol may greatly reduce the effectiveness of crizotinib.

Treatment of Brain Metastases

Brain metastases are a common complication associated with NSCLC, with an estimated 15% of patients being diagnosed with brain metastases within a year of their lung cancer diagnosis. ROS1-positive lung cancer, like all NSCLC, commonly spreads to the brain, leading to lung cancer metastatic to the brain.

Xalkori doesn’t work very well for brain metastases because it does not cross the blood-brain barrier well. The blood-brain barrier is a control system of specialized membranes that work to prevent toxins (as well as chemotherapy drugs) from entering the sensitive environment of the brain.

Rozlytrek appears to have better brain penetration and has shown success in small trials.

Radiation therapy may also offer some hope for ROS1-positive lung cancer that has spread to the brain. Radiation may be given in a couple of different ways:

  • Stereotactic radiotherapy: In this approach, which is also referred to as cyberknife or gamma knife, radiation is delivered to localized spots in the brain.
  • Whole-brain radiotherapy: With this method, the entire brain is treated with radiation.

The choice between these two treatments is an area of debate. Stereotactic radiotherapy—since it only treats a small portion of the brain—has fewer side effects. But whole-brain radiotherapy may offer better outcomes.

At least 75% of people undergoing whole-brain radiotherapy report some improvement in symptoms, and it has been shown to improve overall survival—from one month with no treatment—to two to seven months with treatment.

Drug Resistance

Most cancers eventually become resistant to targeted therapy medications. Your healthcare provider will prescribe a new treatment once your cancer show signs of resistance. But that treatment, too, might become ineffective.

New drugs are being investigated with clinical trials, and there is hope that new treatments will be available in the future.


ROS1-positive lung cancer tends to be aggressive, growing, and spreading fairly rapidly. But it does respond to targeted therapy.

Studies of Xalkori show that the drug offers a disease-control rate of 90%, and those taking the drugs have no progression of the disease for an average of 19.2 months.

The treatment of ROS1 with targeted therapy is not aimed at curing cancer, but it can help you live a longer, more satisfying life by managing the cancer and stopping its spread. More and more, lung cancers with mutations and rearrangements are treated with targeted therapy in a way that's akin to a chronic disease, such as diabetes.

A Word From Verywell

ROS1 is such an uncommon form of cancer that it can be difficult to navigate the "normal" cancer channels. Finding a support group comprised of those who share your diagnosis can help you connect with people who better understand your emotions in relation to your disease and who can help point you towards resources and research.

Look into local and national groups that focus on ROS1 issues, be them in person or online. For example, check out the ROS1 group hosted by Smart Patients. Consider learning about current treatments and geting involved in clinical trials, if possible.

11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading

By Lynne Eldridge, MD
 Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."