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ROS1 Positive Lung Cancer
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ROS1 Positive Lung Cancer

ROS1 positive lung cancer refers to cases of lung cancer in which the patient is positive for a mutation of the ROS1 gene. The ROS1 gene is responsible for making the protein ROS1, which signals cells to grow and reproduce. If a lung cancer patient is ROS1 positive, the cancer is usually more aggressive due to the ROS1 protein causing more abnormal cells to drive the growth of the tumor. However, ROS1 positive patients may be eligible for checkpoint inhibitors for treatment, which block the mutation from causing the cancerous cells to rapidly grow and divide. Although rare, the identification of the ROS1 alteration can play a major role in the patient’s treatment plan. Other than lung cancer, the ROS1 mutation has been identified in the following cancer types:

  • Glioblastoma multiforme
  • Bile duct cancer
  • Ovarian cancer
  • Colorectal cancer

Genetic Testing for ROS1

ROS1-positive lung cancer has only been identified in non-small cell lung cancer (NSCLC), and not in small cell lung cancer. Of NSCLC cases, about 2% of them are ROS1 positive. This has led to an increase in testing for NSCLC patients.

In order to be eligible for targeted therapies, cancer patients need a positive test for the ROS1 mutation. Typically, a tissue sample of the tumor is collected by the doctor and it is sent to a laboratory for results. The tests used for the ROS1 mutation include:

  • Fluorescence in situ hybridization (FISH): The most common testing method used, locates specific DNA sequences by exposing chromosomes to a probe with a fluorescent molecule attached. A researcher will be able to identify if the ROS1 gene if the fluorescent probe has been bound to it.
  • Multiplex real-time PCR assays: Test that covers a range of fusion genes. Inexpensive and quick results compared to other tests. This test uses multiple probes that can be distinguished from the rest of the DNA sequences.
  • Immunohistochemistry: Uses antibodies against the ROS1 protein to detect any abnormalities. This test is for screening to diagnose cancers, so it can be used initially to avoid unnecessary FISH tests.
  • Next Generation Sequencing (NGS): Looks at the entire human genome in one test to detect any mutation. NGS is the most comprehensive test available, but may be expensive and time consuming compared to other testing methods.

ROS1 Positive Lung Cancer Clinical Trials

The only FDA approved treatments for ROS1 positive lung cancer are Crizotinib (Xalkori) and entrectinib (Rozlytrek). These targeted therapies can locate the abnormalities within cells (mutations) to know which cells to attack. This helps treatment avoid damaging healthy cells to minimize side effects compared to standard treatments.

Common side effects of ROS1 inhibitors include:

  • Dizziness
  • Diarrhea
  • Constipation
  • Fatigue
  • Changes in vision

There are also ongoing clinical trials evaluating new therapies for ROS1 cancers. There are both clinical trials specifically for the ROS1 mutation, and many others available to treat lung cancer. Talk with your doctor to see if clinical trials could benefit you. Other drugs available for ROS1 lung cancer cases include Lorlatinib and Ceritinib. These therapies are often taken by themselves or in combination with chemotherapy and other treatments.

Sources:

https://www.cancer.org/lung-cancer

https://www.ncbi.nlm.nih.gov/articles

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