The abnormality in a chromosome is known as ROS1 that usually occurs in the cells of NSCLC. This genetic mutation appears approximately 1-2% of people diagnosed with non small cell lung cancer. The ROS1-positive lung cancer is mainly found in adenocarcinoma subtype of people whose tumors are negative for other so-called driver mutations.
ROS1 rearrangement is basically an aggressive form of lung cancer. It has potential in order to spread quite rapidly. However, with the help of newer medicines are able to manage the disease and able to keep the cancer from progressing for extended periods. This new era's advanced treatment can provide a better prognosis compared to the previous generation treatment options. Signs & Symptoms of the ROS1-Positive Lung Cancer: ROS1 lung cancer is basically related with adenocarcinoma. Adenocarcinoma is known as the most common type of Non-small cell lung cancer. In this cancer the tumors usually develop in tissue right near the outer parts of the lungs. In the early stages of the cancer there are usually no symptoms. When the adenocarcinoma progresses to the point that tumors interfere with the breathing, signs may include:
Causes: The cell genes mainly act as a blueprint for the proteins which are involved in order to regulate the growth as well as division of the cells. When any respective gene is damaged, mutated, or rearranged, it starts producing an abnormal protein, which mainly performs the abnormal functions. There are certain factors that associated with the ROS1-positive lung cancer. Age: The median age of people with ROS1 rearrangements is approximately to be 50.5. Sex: ROS1 is quite common in women, with the occurrences of 64.5%. Smoking history: A higher percentage, approximately 67.7% are never-smokers. Current Testing Method for ROS1-Positive NSCLC: The most common ROS1 fusion partners are CD74, SLC34A2, CCDC6, and FIG. Currently, no FDA-approved companion diagnostic tests exist for ROS1-rearranged NSCLC. There are several methods in order to detect the ROS1 rearrangements such as FISH, IHC, NGS and RT-PCR. FISH: Break-apart FISH can be considered to be the gold standard for detecting the ROS1 rearrangements and can be performed on the biopsy or cytologic specimens. IHC: IHC is the most cost-effective method for detecting the ROS1-positive non small cell lung cancer. Several ROS1 mono- and polyclonal antibodies are commercially available, and at least one exhibits sensitivity close to 100%. However, IHC staining is less specific than FISH, and staining results can be operator dependent. IHC staining can be performed on most tissue types, and ROS1-positive IHC shows diffuse expression in more than 75% of tumor cells with moderate-to-strong staining intensity. RT-PCR: The sensitivity and specificity of RT-PCR for detecting ROS1 rearrangements is high and facilitates the identification of ROS1 fusion partners. However, this assay requires the use of fusion-specific primers and therefore cannot be used to identify novel rearrangements. The use of RT-PCR is also limited by the requirement for good-quality RNA, which may be difficult to obtain from smaller tumor samples. NGS: With the help of NGS doctors get the rapid, high-throughput sequence data from a sample and provide the multiplex testing that enables the simultaneous pooling and sequencing of large numbers of DNA libraries during a single run. The novel as well as known gene fusions of the ROS1 rearrangements may be detected with the help of this assay. Also, there are limitations of NGS such as higher costs, a requirement for more tissue while on processing, and a longer processing time period compared with IHC and FISH. Current Approved Treatment: The ROS1-positive tumours are the third clinically actionable subtype after the EGFR-mutated as well as ALK-rearranged non small cell lung cancer to hold US FDA approval for targeted therapy, the TKI crizotinib. Treatment with the help of tyrosine kinase inhibitors (TKIs), basically targets the ROS1 kinase domain. It is mainly considered as the standard care. Tyrosine kinase inhibitors have been shown to have a robust as well as durable response. Crizotinib: Crizotinib approved as a first-line treatment for patients with the advanced ROS1-positive non small cell lung cancer. This drug is the first FDA-approved agent for treating patients with the metastatic non small cell lung cancer whose tumours contain ROS1 rearrangements. Common side effects: Visual disturbances is the most common adverse effect reported with crizotinib. Ceritinib: The TKI ceritinib is approved for the treatment of patients with the metastatic ALK-positive NSCLC and is being explored for the participants with the advanced ROS1-positive Non Small Cell Lung Cancer. Common side effects: The most common adverse effects associated with the ceritinib treatment include: nausea, diarrhea and anorexia. Entrectinib: Entrectinib is a small-molecule TKI that has been shown to have activity against tumors with ROS1 rearrangements as well as ALK and NTRK1/2/3 rearrangements. Cabozantinib: The preclinical data has shown the drug might overcome crizotinib resistance in ROS1+ cancer in initial studies. However, the required dosage makes the drug difficult in order to tolerate for several patients. Cabozantinib holds the US FDA approval for metastatic medullary thyroid cancer (as Cometriq) and renal cell carcinoma (as Cabometyx). Lorlatinib: Lorlatinib mainly is a third generation TKI. It is active against the ROS1 as well as ALK rearrangements. This medication rationally designed in order to penetrate the blood-brain barrier and overcome ALK-resistance mutations. Lorlatinib recently holds the approval for treating advanced ALK-positive non-small cell lung cancer in those patients whose disease has progressed after the second-generation ALK inhibitor. Read:- EGFR Positive lung cancer
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