Test Will Identify ALK Inhibitor-Resistance Mutations

Some patients develop ALK resistance mutations while under treatment with an ALK inhibitor, making the therapy ineffective, while other patients have existing ALK resistance mutations that render ALK inhibitor therapy ineffective from the start. The test will meet a growing challenge within personalized cancer: the development of tumor resistance to a prescribed drug, and help physicians monitor and make more effective treatment decisions for patients with non-small-cell lung cancer and other ALK-driven drugs.

Cancer diagnostics firm Insight Genetics (Nashville, TN, USA) has received a US$193,000 Small Business Innovation Research contract from the National Cancer Institute (NCI; Bethesda, MD, USA) to develop a companion diagnostic test for drugs targeting ALK.

Under the terms of the NCI contract, Insight Genetics will further the development of Insight ALK Resistance, a clinical diagnostic assay for ALK inhibitor-resistance mutations. The assay is being developed to detect all known ALK inhibitor-resistance mutations using an allele-specific polymerase chain reaction (PCR) platform.

ALK is the cause of a number of cancers and many ALK-inhibiting therapies have been developed. Several ALK inhibitors are in clinical trials, and Xalkori (crizotinib) was recently approved by the US Food and Drug Administration (FDA; Silver Spring, MD, USA).

ALK was discovered by physician-scientist Dr. Stephan W. Morris of St. Jude Children’s Research Hospital, who is a collaborator of Insight Genetics. The Morris lab has identified in preclinical assays a large number of ALK kinase mutations that confer high-level Xalkori resistance, a subset of which have already been reported in patients who exhibited resistance to Xalkori therapy.

"Diagnostic tests are critical not only in helping doctors decipher which cancer therapies are most appropriate for a patient, but also in monitoring if a treatment is effective for that patient,” said Eric Dahlhauser, Chairman and CEO of Insight Genetics. "It is common for cancer patients to develop resistance to their treatments. Our Insight ALK Resistance assay will help improve patient care by providing patients and healthcare providers with valuable, real-time information about the mutation status of ALK in cancers to help guide the prescription of alternate treatments."

The challenge of treatment resistance is leading oncologists to believe that a combination of therapies will probably be needed in most instances to treat various cancers optimally. Insight ALK Resistance will identify inhibitor-resistance mutations and help guide the development and use of next-generation ALK inhibitors for patients resistant to first-generation therapy.

Related Links:
Insight Genetics
National Cancer Institute