Bay Biosciences provides high-quality, fresh frozen biopsy tissue samples. FFPE tissue blocks with matched fresh frozen sera (serum), plasma, and peripheral blood mononuclear cells (PBMC) bio-fluids from patients diagnosed with ROS1-Positive Lung Cancer.
The sera (serum), plasma and PBMC biofluid specimens are processed from ROS1-positive lung cancer patient’s peripheral whole-blood using customized collection and processing protocols.
Fresh frozen tissue and matched biofluid samples are collected from unique patients diagnosed with ROS1-positive lung cancer.
Bio-samples are provided to a valued pharmaceutical customer for research, diagnostics, discovery and drug development.
ROS1-Positive Lung Cancer Overview
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.
Genetic mutation such as 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 about 1% to 2% of people diagnosed with NSCLC.
This type of ROS1-rearranged non-small cell lung cancer (NSCLC) is classified as a distinct molecular subset of NSCLC with a therapeutic target. ROS1 rearrangement is most often identified in never-smokers with adenocarcinoma and EGFR and ALK receptor tyrosine kinase inhibitors (TKIs).
Treatment with tyrosine kinase inhibitors (TKIs), which target the ROS1 kinase domain, is considered the standard of care. TKIs have been shown to have a robust and durable response. However, information regarding the clinical outcomes of TKI treatment, including brain metastasis, remains limited.
Signs and 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:
- Blood in sputum
- Chronic cough
- Fever
- Fatigue
- Headache
- Shortness of breath
Usually these signs begins only after the cancer has spread, adenocarcinoma and ROS1 variations of adenocarcinoma are usually diagnosed when the cancer has reached an advanced stage.
Causes of ROS1-Positive Lung 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.
Following are the risk factors associated with ROS1 positive lung cancer:
- Age: The median age of patients with ROS1 rearrangements is estimated to be 50
- Sex: ROS1 mutations are more common in women patients than male patients.
- Smoking history: Lung cancer patents who smoke have a less percentage of ROS1 positivity compared with patients who don’t smoke, an estimated 67.7% are never-smokers.
Diagnosis of ROS1-Positive Lung Cancer
There are a several ways in which patients 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 mutations, EGFR 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 (TNBC)).
These diagnostics tests will also help identify the stage of the lung cancer, which is important for determining the best course of treatment for a particular type of NSCLC.
Treatment of ROS1-Positive Lung Cancer
If the 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.
These include the following:
- Surgery: Options may include removing some lung tissue, a wedge-shaped piece of lung, a lobe of one lung, or an entire lung.
- Radiation therapy: 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 such as drug Alimta (pemetrexed).
Targeted Therapy
Drugs known as targeted therapies 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 non-small cell lung cancer (NSCLC) who have ROS1-positive lung cancer. These are the following:
- Rozlytrek (entrectinib)
- Xalkori (crizotinib)
These targeted therapy drugs are meant to be taken long term. Patients would only stop taking the medications if the cancer starts to spread (metastasize), which indicates the drug is no longer working. Or if the patient cannot tolerate the medication anymore.
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.
NSCLC 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 few 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 patients 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 doctors 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.
Prognosis
ROS1-positive lung cancer tends to be aggressive, growing, and spreading fairly rapidly. But it does respond to targeted therapy.
Studies of Xalkori (Crizotinib) 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 patients 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.
Bay Biosciences is a global leader in providing researchers with high quality, clinical grade, fully characterized human tissue samples, bio-specimens and human bio-fluid collections.
Samples available are cancer (tumor) tissue, cancer serum, cancer plasma cancer PBMC and human tissue samples from most other therapeutic areas and diseases.
Bay Biosciences maintains and manages its own bio-repository, human tissue bank (biobank) consisting of thousands of diseased samples (specimens) and from normal healthy donors available in all formats and types.
Our biobank procures and stores fully consented, deidentified and institutional review boards (IRB) approved human tissue samples and matched controls.
All our human tissue collections, human specimens and human bio-fluids are provided with detailed samples associated patient’s clinical data.
This critical patient’s clinical data includes information relating to their past and current disease, treatment history, lifestyle choices, biomarkers and genetic information.
Patient’s data is extremely valuable for researchers and is used to help identify new effective treatments (drug discovery & development) in oncology, other therapeutic areas and diseases.
Bay Biosciences banks wide variety of human tissue samples and biological samples including cryogenically preserved at – 80°C.
Including fresh frozen tissue samples, tumor tissue samples, FFPE’s, tissue slides, with matching human bio-fluids, whole blood and blood derived products such as serum, plasma and PBMC’s.
Bay Biosciences is a global leader in collecting and providing human tissue samples according to the researchers specified requirements and customized, tailor-made collection protocols.
Please contact us anytime to discuss your special research projects and customized human tissue sample requirements.
Bay Biosciences provides human tissue samples (human specimens) from diseased and normal healthy donors which includes:
- Peripheral whole-blood,
- Amniotic fluid
- Bronchoalveolar lavage fluid (BAL)
- Sputum
- Pleural effusion
- Cerebrospinal fluid (CSF)
- Serum (sera)
- Plasma
- Peripheral blood mononuclear cells (PBMC’s)
- Saliva
- Buffy coat
- Urine
- Stool samples
- Aqueous humor
- Vitreous humor
- Kidney stones (renal calculi)
- Other bodily fluids from most diseases including cancer.
We can also procure most human bio-specimens and can-do special collections and requests of human samples that are difficult to find. All our human tissue samples are procured through IRB approved clinical protocols and procedures.
In addition to the standard processing protocols Bay Biosciences can also provide human plasma, serum, PBMC bio-fluid samples using custom processing protocols, you can buy donor specific sample collections in higher volumes and specified sample aliquots from us.
Bay Biosciences also provides human samples from normal healthy donors, volunteers, for controls and clinical research, contact us Now.
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