Tumor biopsy-based genetic biomarker test for selecting the appropriate chemotherapy for small cell lung cancer (SCLC) patients.
- Panel allows physicians to predict the responsiveness of SCLC to cisplatin or other platinum chemotherapy agents, thereby avoiding use of potentially ineffective chemotherapies.
- Currently, there is no method for predicting the responsiveness of SCLC to cisplatin.
Platinum-based chemotherapeutic agents are used to treat a variety of cancers including testicular cancer, lung cancer, lymphomas and many others. As the use of platinum-based chemotherapeutics is wide, they are often frontline agents selected to treat the ~1.67 million new cancer cases each year in the US. However, platinum-based chemotherapeutics can often fail and their use can result in profound side effect such as peripheral neuropathy. For example, the rate of failure for cisplatin is as high as 50% in certain cancers like small cell lung cancer (SCLC). Roughly 33,600 new cases of SCLC are expected for 2014 and a method for determining cisplatin sensitivity, and therefore personalizing chemotherapy, for these 33,600 patients would be in high demand.
Chemotherapy-resistant cancers result when individual genetic differences result in the expression of proteins and factors capable of rendering the therapy ineffective are expressed in higher than normal levels. This resistance is often intrinsic to the tumor and results in the drug damaging healthy tissue while leaving the tumor intact. Research correlating differential chemotherapy sensitivity and gene expression allows for understanding of which genes, when expressed at atypical levels, provide protection against a particular therapy. Using multiple SCLC lines and patient samples, Emory researchers analyzed 200,000 genes for their expression levels and uncovered five which were expressed differentially in responsive versus unresponsive cell lines. These 5 genes are GLS (glutaminase), SLC35A3, AURKA (Aurora kindase A), LOC100129585, and UBE2C (ubiquitin conjugating enzyme E2C), and together are predicative of cisplatin sensitivity. Use of this information allows a clinician to assay the expression levels of these genes in tumors and make a patient-specific therapy selections based on this knowledge.