Get ready. The next digital frontier, diagnostics tests that intimately tie together the diagnostic imaging of pathology to the therapeutics of drug treatments, are moving personalized medicine, or personalized healthcare (PHC) closer to reality.
It's commonly accepted that a broad-brush approach in treating diseases doesn't always work. And if there's a disease ripe for PHC, it's cancer. The objective in personalized healthcare for cancer is to identify the right patients with the right molecular change, and then hit that patient's specific molecular change with the right drug. Several upcoming cancer tests will help usher in a renaissance in diagnostics.
How diagnostic tests will look in the future
These companion diagnostic tests exist today. HER2/neu status is the most common example, where pathologists provide information about the protein or gene copy number that determines whether Herceptin treatment is indicated. Today most pathologists read those tests manually, but this practice is poised to change, along with pathologists becoming a driver of personalized healthcare.
The biggest change in the next five years will be driven by tissue-based assays that are becoming more molecular - and complex. For example, 10 years ago non-small cell lung cancer (NSCLC) was considered a single disease from the therapeutic perspective - while its many subtypes appeared histologically different to the pathologist, these subtypes were all lumped together for the purpose of treatment. Ten years later, the genetic underpinnings driving the uncontrolled growth of more than half of NSCLCs can be explained on a molecular level. One breakthrough has been the identification of anaplastic lymphoma kinase or ALK. Early trial results show significant tumor shrinkage in more than one-half of patients given a clinical drug that inhibits the activity of the ALK enzyme.
An ALK diagnostic test, being developed alongside the drug's procession through late stage clinical trials, would be performed on all NSCLC patients, with the test outcome determining if anti-ALK therapy is indicated. Other tests performed at the same time would detect other mutations or gene amplifications, such as those involving the epidermal growth factor receptor (EGFR), which also determine therapeutic response.
With the use of multiple markers and diagnostic modalities on a single slide, a single multiplex test or assay will provide information on specific genetic events and also on the levels of protein and the presence of specific mutated versions of a protein, resulting in the stratification of patients into therapy regimens.
Tools and technologies are being developed that will help pathologists interpret these next generation assays, enabling them to view the images on desktop monitors, using image analysis algorithms to analyze them and provide more quantitative, accurate and reproducible results.
In addition, technology advances will allow these molecular tests to move from the few specialized labs doing them today to standard labs, using readily available platforms for test preparation and interpretation.
Changing role for pathology departments
The delivery of this tissue-based molecular profiling for personalized healthcare could become the domain of subspecialty labs, with community and hospital-based pathologists observing from the sidelines. Or, with the enabling imaging technologies and staining platforms already available in the market, it could become part of every pathologist's practice.
Strongly supported by oncologists, this pivotal role of the pathologist as the focal point in the delivery of personalized healthcare is also backed by an initiative from the College of American Pathologists, with a subset of pathologists already leading the change. Today, Massachusetts General Hospital pathologists meet with cancer patients to help them understand their pathology reports. In the future, pathologists will utilize advanced workstations to aggregate laboratory, radiology, and molecular data with pathology data, including these multiparameter, multiplex assays, in an integrated report that guides decisions for each patient by defining therapeutic targets and prognosis.
The sooner that pathologists become comfortable with these new tests and imaging technologies, the sooner they will be ready to embrace their new and exciting role in personalized healthcare.
Dr. Robert Monroe, Chief Medical Officer at BioImagene, Inc., acquired by Ventana Medical Systems Inc., is a board certified pathologist with over 10 years of experience in anatomic pathology, cytopathology, and biomedical research, who leads the company's clinical studies on companion algorithms and digital pathology applications.
Dr. Eric Walk, Senior Vice President and Chief Medical Officer at Ventana Medical Systems, Inc., a member of the Roche Group, is a molecular and translational pathologist with over 10 years of experience in clinical diagnostic pathology, oncology drug development, oncology translational medicine/biomarker development and diagnostics.