The drug Xalkori, generic crizotinib, was approved last year for the treatment of patients with late-stage, non-small cell lung cancers (NSCLC) who express the abnormal anaplastic lymphoma gene (less than 7% of patients). An unknown number of pleural mesothelioma patients also express this abnormal gene, so they could be benefitted by treatment with this drug.
Chemotherapy is currently the most common treatment for patients with NSCLC or mesothelioma, helping to slow disease progression and manage symptoms. However, both diseases have proven to be resistant to chemotherapy at times.
Now, researchers have identified a biomarker that identifies “a key gene that determines resistance to a range of cancer drugs.” The researchers state that this biomarker may be able to help them predict patient responses to drugs and also provide doctors with a better strategy to treat chemo-resistant cancers based on patients’ genetic characteristics.
The National Cancer Institute defines a biomarker as “a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.” Not only can biomarkers be useful in the treatment of diseases, they can also be beneficial in the diagnosis of diseases such as mesothelioma.
Study Author Rene Bernards of the Netherlands Cancer Institute states that the researchers’ goal was to understand why some patients are resistant to crizotinib. They found that when the MED12 biomarker was suppressed, the transforming growth factor beta receptor (TGF-betaR), a protein involved in cell growth and cell death, was enhanced.
When TGF0betaR signaling in MED12-defficient cells was inhibited, responsiveness to drugs was restored.
According to Bernards, ““We need to understand the mechanisms of drug resistance to effectively prevent it from occurring in the first place,” says Bernards. “We have shown that blocking this escape route restores sensitivity to the original drug, suggesting a way to treat patients that have undergone this type of drug resistance.”