Methods of drug discovery and novel therapeutics have evolved greatly over the last decade, paralleled by advances in diagnostic tools. Although there are currently multiple methods of diagnosing and staging cancers based on tissue histology, only recently has the idea of molecular cancer diagnosis and profiling gained traction and acceptance. Presentations at the upcoming Cambridge Healthtech “Molecular Diagnostics Conference” in San Francisco will cover the latest in molecular diagnostics.
Stephen Little, CEO at DxS (www.dxsgenotyping.com), notes that acquired mutations in genes, such as EFGR and K-RAS, seem useful in diagnosis, prognosis, and therapy selection in cancer. “There is a trend in the industry to move away from cytotoxic drugs to targeted therapies,” says Little. “And the need for tests to target these drugs correctly is the focus of what we do. Our products detect mutations in tumors to predict drug response.”
Because mutations are localized to the tumor, there are specific technological challenges associated with their detection. “There is a need for diagnostic technologies with sufficient selectivity to allow the detection of mutations within a high background of unmutated DNA,” says Little. “Real-time allele-specific PCR is a simple method that allows the detection of low numbers of mutant genes in high backgrounds of normal DNA.
“When you are looking at inherited SNPs, you either carry them in all of your cells or none. But tumors are different; when you’re looking at cancer, you need to see the mutations against the background. This technology has been applied to several oncogene targets to develop selective and reliable diagnostic assays for EGFR, RAS, and RAF genes, as well as others.
“One emerging way to find these genes is in the plasma. When dealing with certain cancers, particularly cancer of the lung, biopsies are hard to obtain. It is well-known that the blood of cancer patients carries soluble DNA derived from the tumor so you can run one of these assays using DNA from blood, and that will help detect the mutation,” says Little. “And hence determine the course that therapy should take.”
Another application of the kits is monitoring the development of the tumor. As the tumor grows and develops, new mutations appear. Therefore, the idea of tracking the tumor and changing the treatment to vary with the appearance of these new mutations is taking hold. “Of course this approach only makes sense in the context of new therapies. What is particularly exciting at the moment is the combination of new therapies and new diagnostic tools that make this whole approach feasible,” adds Little.